Lecture 1- Physiology of Neurons

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Cell Bio

Lecture 1
-

Physiology of Neurons

Morphology of a Typical Neuron

-

Cell body,
dendrites,

and

axon
s
-

dendrites

bring info towards the cell body, axon takes info from
the neuron away to the seco
ndary neuron or the target cell; long fiber

-

Blue = myelin

sheath (insulation) and helps carry inform
ation better and don’t lose it

o

M
ade up of lipids

-

Synaptic terminal is
at the end where neurotransmitters are released and picked up by
receptors on post
-
synaptic side to

go to

ion
-
gated channels

-

Slide 3

Myelin She
aths of Axons

-

Myelinated axons in the central nervous system

o


A single oligodendrocyte
(G)

emits several processes, each of which winds in a spiral
fashion around an axon to form the myelin sheath.

-

Myelinated axon i
n the peripheral nervous system

o


A Schwa
nn cell forms a myelinated sheath for peripheral axons in much the same
fashion as oligodendrocytes do for central ones, except that each Schwann cell
myelinates a single axon.

-

The myelin from a single oligodendrocyte ends before the next wrapping from an
other
oligodendrocyte.

-

The bare axon between sheaths is the node of Ranvier
(N).


o

The node of Ranvier
(N)

is shown between adjacent sheaths formed by two Schwann
cells (
S
1 and
S
2).

o

Axon potential jump through these

-

Conduction of action potentials is salt
atory down the axon, skipping from node to node.

-

Axonal heloc will have many numbers of sodium channels because
that’s
where action
potentials start

-

Slide 4

Major Light and Electron Microscopal Features of Neurons

-

Dendritic spines
-

so
me genetic diseases i
f they are not present

o

Mental retardation
because they cannot store memory as well as
others

o

Have calcium channels

Neuron
-

the Axon

-

Projects from the cell body at the site of the axonal hillock (or initial segment)

-

Carries impulse
away

from the cell body

-

May be myelinated or not myelinated

-

Contains numerous Na
+

channels

Axonal Degeneration and Regeneration

-

Step 1: Degeneration of
synaptic terminal distal to lesion

-

Step 2: Wallerian
degeneration

-

Step 3: Myelin degeneration

-

Step 4: Scavenging of debris

-

Step 5: Chromatolysis

-

Step 6: Retrograde
transneuronal degeneration

-

Step 7: Anterograde transneuronal degeneration

-

All neurons are aligned, but
if the
one in the middle is damage
d

on the axon, this will affect the
neurons distally as well as proximally.

-

Terminal parts of the axon won’t have communication with the cell body and therefore begins
to degenerate (Wallerian degeneration).

-

Myelin sheath is damaged and mac
rophage
s come to the area and begin engulfing the myelin
sheath

-

Neuron distal to the lesi
on will also start to degenerate (ER)
-

chromatolysis because not
receiving any information

-

Slide 7

Regeneration

-

The rate of regeneration is limited by the rate of slow axonal transport to about 1 mm/day

-

In the PNS


axon becomes damaged there is still a ch
ance the distal part of the axon and the
cell body can regenerate (6 months to a year) and recover some function.

-

Axon sproutings stretch to the opposite end and join to re
-
establish communication. Schwann
cells will also come and re
-
wrap them.

Neuronal Cytoskeleton

-

Is important for transport, maintaining shape/structure, and compartmentalizing the cell

o

Microtubules

o

Neurofilaments

o

Microfilaments

-

Cytoskeleton is h
ow to bring ACh and internal components places.

o

Microtubules have pathways, and

d
ynein and
k
inesin carry vesicles filled with
neurotransmitters down microtubule
s

o

T
he anterograde movement (cell body to the end) is maintained by kinesin and from the
terminal back to the cell body is maintained by dynein


Shingles

-

After infection with ch
ickenpox the varicella
-
zoster virus becomes dormant in dorsal
-
root
ganglia, only to reactivate later when the immune system no longer contains it. Such
containment failures are more likely with age and with immunocompromised states, and this
produces the c
lassic appearance of shingles in a dermatomal distribution.

-

It may also cause postherpetic neuralgia, a disabling condition of chronic pain that is difficult to
manage.

-

Herpes Simplex Virus Type 1 capsid protein VP26 interacts with Dynein Light Chains RP3
*

and
Tctex1 and this plays a role in viruses retrograde cellular transport.

-

Toxins and viruses etc have a chance to interact with the dynein and be carried back to the cell
body

-

Shingles


virus remains dormant and is carried on the dynein back to cell b
ody;
immunocompromised virus returns in the dermatome to give shingles

Peripheral Nerve

-

As an antioxidant,
Vitamin E

supports normal peripheral nerve function by preventing damage
to Schwann cells and dorsal root ganglia

-

Axons of different types are bou
nd together with loose connective tissue called endoneurium.
These are in turn bound together into a fascicle by a connective tissue sheath called
perineurium. The perineurium provides structural stability to the nerve

-

However, strength is increased even m
ore by a third connective tissue layer called the
epineurium. Within a single nerve, the axons may shift from one fascicle to another as the
nerve traverses the body. The intertwining of the axons results in intertwining of the fascicles
which adds furth
er strength to the nerve

-

Peripheral nerves will have motor efferent and sensory afferent bundled together

Neuron
-

the pre
-
synaptic terminal

-

If you shoot the cell with an action potential
, the

first channels to open will be calcium channels
on the presynapt
ic side.

-

Calcium goes in pre
-
synaptic terminal and helps docked vesicles to fuse to the pre
-
synaptic
membrane and release neurotransmitters.

-


Neurotransmitters go to receptors on post
-
synaptic membrane. Receptors can be ion
-
gated
(nicotinic) or G
-
protei
n coupled (muscarinic)

-

Slide 14

Myasthenia Gravis

-

Is an autoimmune disease in which antibodies bind to acetylcholine receptors at the
neuromuscular junction, thereby disrupting their functionality and causing them to be more
rapidly degraded

-

The weakness
is characterized by rapid tiring of the muscle with repeated use

-

Median age range of onset is 15
-
35 years of age

-

Fatigue and eye muscle weakness are the prominent symptoms of the disease

-

Patients are treated with acetylcholinesterase inhibitors to increase

the concentration of ACh in
the synapse. A higher concentration increases the probability that ACh will bind to its receptors.

-

IV administration of edrophonium or neostigmine, drugs that block the breakdown of
acetylcholine by acetylcholinesterase, tempo
rarily increases the levels of acetylcholine at the
neuromuscular junction.

o

Edrophonium is for short term and diagnosing

-

No
where for ACh to the go and end up with muscle weakness because they can’t respond.

Depolarization

-

Excitatory input to a neuron usu
ally generates a flow of positive charge across the dendritic
membrane

-

Because the interior of a resting neuron is polarized negatively, this inward current
depolarizes

(makes the membrane voltage more positive) the cell

o

Open sodium and close potassium

-

S
lide 17

Basic Properties of Action Potentials

-

Hyperpolarizing


trying to make more negative so either let potassium channels leak or bring
Cl
-

from outside to inside

-

Slide 18


-

If we didn’t have action potentials stimulus would degr
ade as distance increased

-

W
ith potentials still have same amount of stimulus, but just a little bit delayed as you get further
away

-

Slide 19

Signal Conduction in Dendrites

-

The change in membrane potential (Vm) caused by a neurotransmitter at the postsynaptic
membrane is called
pos
tsynaptic potential

(PSP).

o

If the neurotransmitter is excitatory, it produces a
depolarizing

Excitatory PSP

(
EPSP
).

o

If the neurotransmitter is inhibitory, it produces a
hyperpolarizing

Inhibitory PSP

(
IPSP
).

Excitatory Post
-
synaptic Potentials

-

Postsynaptic increase in sodium or calcium conductance
,
Na
-

most prevalent
-

leads to
depolarization just as for action potential

o

Using calcium for depolarization is usually for cardiac cells

-

Postsynaptic decrease in potassium conductance,


o

Both increase
the positive charge in the cell =
EXCITATORY


Inhibitory Post
-
synaptic Potentials

-

Increased potassium efflux or chloride influx,

b
oth decrease the positive charge in the cell =
more negative =
INHIBITORY


Spatial vs. Temporal Summation of ESPSs

-

Spatial summation is the adding together of EPSPs or IPSPs over
SPACE


o

C
an have many different axons coming and touching and dendrites gather similar
information, so in space you sum up info

-

Temporal summation is the adding together of EPSPs and IPSPs over

TIME


o

O
ne neuron touching another neuron but keeps sending the same information

-

The action potential will always be the same shape and amplitude; but you can increase the
frequency so it is understood by the secondary cell as a more important signal

-

Slide

23

Attenuation of ESPSs in Dendrites

-

The thicker and shorter the dendrite, the more likely is a dendritic ESPS to trigger an action
potential at the axon hillock

-

If your dendrites are shorter and thicker its better; longer and thinner is worse

-

Larger diam
eter means less resistance

-

Slide 24

Dendritic Membranes Have Voltage
-
Gated Ion Channels

-

In c
erebellar Purkinje cells, the dendrites may fire slow Ca2+ action potentials >> can propagate
toward the soma, but do
not

continue down the axon.

-

These slow Ca2+
action potentials may trigger fast Na+
-
dependent action potentials in the soma
and initial segment.

Calcium and Sodium Action Potentials

-

Dendrites usually do not fire AP, however in Purkinje cells the high density of voltage
-
gated
calcium channels in the d
endrites allows the generation of slow dendritic calcium spikes, which
propagate to the axon soma

-

Even when we use sodium channel
blockers and still have action potential spikes due to calcium

-

Some neurons generate spontaneous spiking activity, even withou
t dendritic input (i.e.,
magnocellular neurons of hypothalamus)

-

The key for this type of behavior is ion channels with slow kinetics (e.g., Ca
2+

channels) in
addition to those with the typically fast kinetics (e.g., Na
+

channels).

-

Pictur
es on slide 26/27


Repetitive Spiking Patterns of Neurons

-

The neuron's response to dendritic inputs varies in both the shapes of single action potentials
and different repetitive firing patterns

-

D
o not adap
t


Na and K channels

-

A
dapt strongly


Na and K channels another set o
f K channels

(activate very slowly)

-

R
hythmic bursts

-

Adaptation


example,
put watch on your wrist and you know it is there at first, but after a
while you do not notice it

i
s there because of sensory adaptation; while the info is still
maintained it is not
at the conscious level unless it changes

-

Slide 28

Axonal Conduction

-

Axons are specialized for rapid, reliable, and efficient transmission of electrical signals

o

Myelinated axons are specialized for reliably and rapidly carry electrical signals from one
pl
ace to other places, in the form of action potentials

-

An action potential starts at the initial segment >> due to high density of voltage
-
gated Na+
channels.

-

All
-
or
-
none principle:

o

A neuron fires with the same potency each time

o

Frequency for firing can
vary

o

It either fires or not; it cannot partially fire

o

Can travel very long distances

-
Self
-
propagating



Axons vary in diameter, and may have myelin

-

Conduction velocity of a myelinated axon increases linearly with diameter

-

Axons are larger than about 1

m

in diameter are all myelinated

-

Proprioception
-

where your joints are during the day; thick axons because it is very important
information and you don’t want the information to be lost or delayed (A
-
alpha)

-

A
-
beta
-

mechanoreceptors (presssure applied)

-

A
-
de
lta
-

sharp pain

-

C
-

unmyelinated fibers; chronic pain

-

Slide 31

Demyelinization

-

Remember
un
myelinated

and
de
myelinated

are different !!

-

Demyelinated axons conduct action potentials slowly, unreliably, or not at all

-

Demyelinating diseases of the CNS:

o

Multiple sclerosis,

o

P
rogressive multifocal leukoencephalopathy,

o

C
entral pontine myelinolysis

-

Demyelinating diseases of the peripheral nervous system:

o

Landry
-
Guillain
-
Barre syndrome

-

Unmyelinated
-

meant to be not have myelin sheath

-

Demyelinated
-

supposed

to have myelin sheath, but disease has caused it to disappear

o

Axons are still healthy, but no myelin sheath

-

Can give you multiple problems; neuron doesn’t know what is going to happen

-

Action potential can
pass through, completely block parts of conduction

-

Problem with one axon myelination it will affect neighboring cells too

-

Slide 35


Multiple Sclerosis

-

The most common demyelinating disease of the central nervous system.

-

An autoimmune disease directed against the myelin or oligodendrocytes.

-

Unclear trig
ger, more common in women than in men

-

Typically have diplopia/vision problems and more common in Afri
can Americans

-

Characteristic of many patients with MS is remissions and relapses

o

An exacerbation is due to the occurrence of active inflammation of a white

matter tract
in the CNS.

o

A remission occurs when the inflammation subsides and the demyelinated axons
recover some of their function, and are able to conduct action potentials through the
area of myelin damage.

Demyelinating Disease of the Peripheral NS

-

Landry
-
Guillain
-
Barre Syndrome:

o

Following a respiratory, or other viral or mycoplasmal infection, an ascending neurologic
syndrome develops

o

Typically have a viral illness 2
-
3 weeks prior

o

Starts with weakness, leads to paralysis of the legs >> subsequent i
nvolvement of the
hands and arms

-

It may involve the paralysis of the nerves feeding the brain stem >> requires mechanical
ventilation

-

Initial stage reaches a plateau, then gradually resolves

-

Pathology: segmental demyelination in PNS

Lecture 2
-

Neuronl
Microenvironment

BECF and CSF

-

Neuronal microenvironment includes the extracellular fluid (ECF), capillaries, glial cells, and
adjacent neurons

-

The concentration of solutes in
brain ECF

(BECF) fluctuate with neural activity. Similarly, changes
in BECF can i
nfluence nerve cell behavior

o

Blood
-
brain
-
barrier (BBB) protects BECF from fluctuations in blood composition

o

The cerebrospinal fluid (CSF) strongly influences the BECF composition

o

The surrounding glial cells “condition” the BECF

-

Brain ECF and CSF are not t
he same thing; brain ECF
is the
regular tissue/extra
-
cellular area
maintained by the blood circulation

-

BBB
-

endothelial cells wrap over thems
elves so nothing can go between


o

S
ubstances must go through endothelial cells to brain ECF because it must be close
ly
monitored and maintained.

o

Once we lose a neuron we cannot make it again

Cerebrospinal Fluid

-

CSF is a colorless, watery liquid which fills the ventricles of the brain and forms a thin layer
around the outside of the brain and spinal cord in the subarac
hnoid space

o

CSF is secreted by a highly vascularized epithelial structure,
choroid plexus

-

The
ventricles

of the brain are four small compartments

o

Each contains a
choroid plexus

and is filled with CSF


Ventricles and Subarachnoid Space

-

The two
lateral
ventricles

are the largest and each communicate with the
third ventricle

via the
two interventricular
foramina of Monro

-

The third ventricle communicates with the
fourth ventricle

by the
cerebral aqueduct of Sylvius

-

The fourth ventricle is continuous with

the central canal of the spinal cord

-

CSF escapes from the fourth ventricle and flows into the subarachnoid space via three foramina

o

Two laterally placed
foramina of Luschka

o

Midline opening in the roof of the fourth ventricle,
foramen of Magendie

-

CSF in
the brain can only

be 150 mL, but we make 500 mL

-

M
ust renew CSF 3x per day by dumping old
CSF
into venous system

-

Need the CSF to give the brain some cushioning
, especially in cases of trauma

Cerebrospinal Fluid Circulation

-

Superior sagittal sinus is where
the CSF enters the venous drainage by traveling through the
arachnoid granulations

-

Slide 6

The Meninges

-

The brain and spinal cord are covered by three membranes:

o

The innermost layer is
pia mater

o

The middle is
arachnoid mater

(membrane)



B
etween the arachnoi
d mater and pia mater is the subarachnoid space (filled
with CSF)

o

The outermost layer is
dura mater

Pia Mater

-

The
pia mater
is a thin layer of connective tissue cells

-

Very closely applied to the surface of the brain and covers blood vessels

-

The glia limi
tans adjoins the pia from the brain side and is separated from the pia by a basement
membrane

o

Pia adheres associated glia limitans very tightly; this combined structure called the pial
-
glial membrane

Arachnoid Membrane and Dura Mater

-

The cells of the
arach
noid membrane

are linked together by
tight junctions

o

The arachnoid isolates the CSF in the subarachnoid space from blood in the overlying
vessels of the dura mater

-

The
dura mater

is a thick, inelastic membrane that forms an outer protective envelope around

the brain

o

The dura has two layers that split to form the intracranial venous sinuses

-

Sub
-
arachnoid space


a
lso area for lumbar punctures to test CSF for bacterial vs. viral
meningitis

Arachnoid granulations

-

Have one way valves to the sinuses

-

Pressure push
es fluid through arachnoid granulations

Choroid Plexuses Secrete CSF

-

Most of the CSF is produced by the
choroid plexuses

which are located in ventricles

o

Capillaries also form a small amount of CSF

-

CSF production is 500 ml/day >>>
CSF volume of 150 ml

is replaced three times a day

-

CSF percolates throughout the subarachnoid space, then absorbed into venous blood from the
superior sagittal sinus

Secretion of CSF

-

Choroid epithelial cells are bound to one another by tight junctions, which makes the epithel
ium
an effective barrier to free diffusion

-


Ion concentration of CSF is rigidly maintained

-


Micronutrients are selectively transported

-

No between the cell passage, all must go through the cells directly

-

Slide 15



Composition of CSF

-

Table on slide 16

-

If y
ou look at Na and Cl ratio is almost 1, but proteins are very small; so if you see proteins in a
sample of CSF it is an indication of possible bacterial meningitis

Absorption of CSF

-

T
he sites of absorption are specialized evaginations of the arachnoid memb
rane into the venous
sinus “
arachnoid

granulations/villi


Hydrocephalus

-

Hydrocephalus


excessive CSF in cranial cavity

-

Communicating Hydrocephalus


impairment of reabsorption in arachnoid villi or of flow in
subarachnoid space

o

A
ll of the ventricles and
its parts are in communication, but there is a problem with the
emptying of the fluid

-


Noncommunicating (obstructive) hydrocephalus


obstructions of flow within ventricular
system

o

Usually cerebral aqueduct

-

An
y

swelling in the brain
means something

has to
give

-

Example
-

herniation of brain tissue through foramen magnum (can remove chunks of skull to
allow for swelling)

-

In babies, not all sutures have fused so the ventricles can swell and pushes bones outwards

-

Treated with shunts (ventricles to abdominal
cavity), problems with growing children and clogs

“Normal
-
Pressure” Hydrocephalus

-

Spinal tap reveals normal pressure readings, but MRI of the head will show enlargement of all
four ventricles

o

An infection or inflammation of the meninges damages arachnoid v
illi, and causes
impaired CSF absorption

-

Patients typically have progressive dementia, urinary incontinence, and gait disturbance

-

CSF shunt to venous blood or to the peritoneal cavity helps reducing CSF pressure

-

Usually seen in the elderly; still have too
much fluid and ventricles are enlarging and pushing
against the brain tissue itself, but the pressure is not getting higher because it is increasing
within the system.

o

Ventricles push
the internal capsule causing lower motor neuron

disturbances
(incontin
ence and gait) and then hippocampus affected causing the dementia

Lumbar Puncture

-

Procedure to collect CSF from subarachnoid space is called
lumbar puncture


-

The spinal cord ends as a gradual taper, known as the conus medullaris, typically coming to an
end

at the lower border of L1 or at the upper border of L2.

o

The nerve roots of the cauda equina “sprout” from the conus medullaris and extend
caudally within the vertebral canal as far as the caudal end of the sacrum.

-

Spinal nerves exit the vertebral canal
inferior to their named vertebrae, except for cervical spinal
nerves, which exit through the intervertebral foramina superior to their named vertebrae

The Extracellular Space

-

The average width of the space between brain cells is 20 nm

-


Glial cells express
neurotransmitter receptors, and neurons have extrajunctional receptors >>>
capable of receiving messages sent via BECF

o

Numerous trophic molecules secreted by brain cells diffuse in the BECF to their target
cells

-

Green parts are leaky brain areas or circum
-
ventricular organs; specialized areas of the brain are
the same as the rest of the body (for example can know what is the pCO2 concentration

in the
brain
)

-

Slide 22

Blood
-
Brain Barrier

-

CNS blood vessels exclude certain substances from brain tissue :

-

“blood
-
brain barrier”

-


Brain needs to be protected from the constituent variations of blood

-

Area postrema
-

emesis area for toxins/poisons


measures and activates if you need to vomit or
drink water etc

-

Neurons within the circumventricular organs are directly
exposed to blood solutes and
macromolecules

-

Part of neuroendocrine control system for maintaining osmolality, appropriate hormone levels
etc.

-

Humoral signals are integrated by connections of circumventricular organ neurons to endocrine,
autonomic, and be
havioral centers within the CNS

The BBB Function of Brain Capillaries

-

Brain capillary endothelial cells are fused to each other by tight junctions

o


The tight junctions prevent water
-
soluble ions and molecules from passing from the
blood into the brain via paracellular route

o

Electrical resistance of the cerebral capillaries is 100 to 200 times higher than other
systemic capillaries



Glial Cells

-

The
three major types of glial cells in the CNS are astrocytes, oligodendrocytes, and microglial
cells

-


Glial cells are about 10
-
fold more numerous than neurons, and they can proliferate throughout
life

-

Astrocytes are most important; fibrous and may

be

importa
nt scaffolding cells in the
development of the nervous system and directing neurons where to go (arms out and need to
go away from the periphery)

-

Slide 26

Astrocytes

-

Astrocytes modifies and controls the immediate environment of neurons

o

Fibrous astrocytes h
ave long, thin and well defined processes

o

Protoplasmic astrocytes have shorter, frilly processes

-

The cytoskeleton of all the astrocytes composed of a unique protein “
glial fibrillar acidic protein


-

During development, radial glial cells are present:

o

C
rea
te an organized scaffolding by spanning the developing forebrain from the ventricle
to the pial surface

-

Müller cells are retinal astrocytes

-

Bergmann glial cells are located in the cerebellum

-

Astrocytes contain all the glycogen present in the brain

o

A
lso co
ntain all the enzymes needed for metabolizing glycogen

-

The brain’s glucose needs is supplied by blood, in the absence of glucose from blood, astrocytic
glycogen could sustain the brain for about 5 minutes

o

Glucose/glycogen storage in astrocytes; brain loves glucose and astrocytes have a depot
of glucose in case there is an emergency need from the neurons

o

Astrocytes convert glucose into lactate and neurons can convert it into pyruvate to
make ATP; happens wh
en high brain activity in a certain area or when there is a loss of
communication

-

Astrocytes break glycogen down to glucose and even further to lactate, which is aerobically
metabolized by nearby neurons >>>
substrate buffering

-

Slide 30

Astrocytes Help Re
gulate Potassium

-

Astrocyte Vm is about
-
85mV, compared to resting neuronal Vm of
-
65mV, thus glial membranes
have higher K
+

selectivity (equilibrium potential for K
+

is
-
90 mV)

-


The accumulation of extracellular K
+

that is secondary to neural activity serv
e as a signal to glial
cells which is proportional to the extent of the activity

-

Small increases in [K
+
]
o
cause astrocytes to increase their glucose metabolism and provide more
lactate for active neurons


-

Regulate K+ around neurons.

o

When trying to study
the constant activity of hippocampus and frontal lobe puts a lot of
K+ outside the cells because of constant action potentials.

o


If you want to study for prolonged period of time someone needs to take K+ away (not
neuron) so function can continue (constan
t action potentials).

o

Astrocytes like K+ more than neurons so they will take in more

o

Slide 31

Astrocytes Couple to Each Other Via Gap Junctions

-

The network of astrocytes functionally behaves as a
syncytium

o

S
trong coupling ensures that all cells in the a
ggregate have similar intracellular
concentrations of ions and small molecules

o

T
he coupling among astrocytes also play a role in controlling [K
+
]
o

via
spatial buffering

-


The K+ taken up by an astrocyte in a region of high [K
+
]
o
can move through astrocytes
via gap
junctions, and exit into a region of low [K
+
]
o


-

Pass to distal astrocyte who will take it and carry it away

-

Slide 32

Role of Muller Cells in Spatial Buffering

-

Ret
ina has 7 layers

-

Muller cells help to get rid of light and disperse it and help with
potassium moving away from
maculla to assist in homeostasi
s

-

Slide 33

Astrocytes Synthesize Neurotransmitters

-

Astrocytes synthesize at least 20 neuroactive compounds, including glutamate and GABA

-

Glutamate precursor glutamine is manufactured only in astrocytes, by astrocyte
-
specific enzyme
glutamine synthetase

-

Glutamine is released by astrocytes to the BECF to be taken up by neurons

Role of Astrocytes in the Glutamine
-
Glutamate Cycle

-

Astrocyte tak
es glutamate and with glutamine synthetase it will make glutamine which will go to
nerve, which has glutaminase to make glutamate to reuse it

-

Glutamine is also important for the GABA synthesis

o

Neuronal
glutamic acid decarboxylase

converts glutamine to GABA

-

After its use as neurotransmitter by neurons, some of glutamate is taken by up into astrocytes
via high
-
affinity uptake systems

o

This system maintain extracellular glutamate concentration around 1uM

-

If transmembrane ion gradients break down under pathologi
c conditions, high
-
affinity uptake
systems may work in reverse

-

With GABA can come up with a completely different neurotransmitter (glycine)

-

Slide 35

Other Information

-

Excessive accumulation of glutamate in the BECF

induced by ischemia, anoxia, hypogylcemi
a,
or trauma
-

can lead to neural injury

-

In anoxia and ischemia, the sharp drop in cellular ATP levels inhibits the Na
-
K pump and leads to
large increases in [K
+
]
o
and

[Na
+
]
i

o

These changes result in membrane depolarization along with a burst of glutamate

release from vesicles

-

The inability of astrocytes to remove glutamate from the BECF under these pathologic
conditions makes extracellular glutamate levels too high to become toxic for neurons

-

Any time any of these conditions occurs there can be neural in
jury due to accumulation of
potassium and then there is a decrease in pH of the body;
making it
less likely they will fire and
continue their jobs

Oligodendrocytes

-

The primary function of oligodendrocytes in the CNS is to provide and maintain myelin sheath
s
on axons

o

Myelin is the insulating electrical tape of the nervous system

-

Oligodendrocytes in white matter

has 15 to 30 processes, each connecting a myelin sheath to

-

the oligodendrocyte’s cell body

-

Each myelin sheath wraps many

times around the long axis of one axon

-

Oligodendrocytes and myelin contain most of the enzyme carbonic anhydrase in the brain

o

Carbonic anhydrase is important in CO2/HCO3
-

buffer system

o

In the case of glaucoma, use carbonic anhydrase inhibitors to block
production of fluid

-

pH imbalance in the brain reduces seizure threshold

-

Oligodendrocytes are also involved with iron metabolism

Schwann Cells

-

In the Peripheral nervous system, a single Schwann cell provides a single myelin segment to a
single axon of a my
elinated nerve

-


The constituent proteins in PNS and CNS myelins are somewhat different

Microglial Cells

-

Microglial cells derive from cells related to the monocyte/macrophage lineage

o

Microglia represent 20% of the total glial cells within CNS

-

These cells ar
e rapidly activated by injury to the brain, proliferate and become phagocytic

-

Microglia are also the most effective antigen
-
presenting cells within the brain


Lecture 3
-

The Autonomic Nervous System

The ANS

-


The autonomic nervous system is responsible for

maintaining the internal environment of the
body (homeostasis).

-


Within the autonomic nervous system, two neurons are required to reach a target organ,

o

P
re
ganglionic neuron and a
post
ganglionic neuron.

-


The preganglionic neuron originates in the central

nervous system >> it forms synapse with the
postganglionic neuron, the cell body of which is located in ganglia.

-


The autonomic nervous system is divided into the
sympathetic

and
parasympathetic

systems.

-

Always a ganglion in the middle

-

Sympathetic
-

para

or peri
-
spinal ganglia; parasympathetic
-

ganglion near or at target organ

Sympathetic System

-

The
sympathetic system

is catabolic (burns energy)

-

The sympathetic nervous system is also called the
thoracolumbar

system because the ganglia
are located lateral
to the vertebral column in the thoracic and lumber regions (T1
-
L3)

-

Because the ganglia are fixed along the back, the postganglionic sympathetic fibers can be quite
long

-

Within the sympathetic system the preganglionic axons form synapses with many postgangl
ionic
cells, therefore giving this system a widespread action

-

At the ganglion, sympathetic system uses norepinephrine to stimulate adrenergic receptors

Parasympathetic System

-

T
he
parasympathetic system

is anabolic (tries to conserve energy)

-

The cell bodies

of preganglionic parasympathetic neurons are located in specific nuclei of the
medulla, pons, midbrain, and in the S2 through S4 level of the spinal cord.

o

B
rain >> with four cranial nerves: the oculomotor nerve (CN III), the facial nerve (CN VII),
the gl
ossopharyngeal nerve (CN IX), and the vagus nerve (CN X).

o

S2

S4 >> the pelvic splanchnic nerves.

-

The parasympathetic system:
craniosacral


The Preganglionic Parasympathetic Neurons

-

CN III, VII, and IX originate in three groups of nuclei:

o

T
he
Edinger
-
We
stphal nucleus

>> subnucleus of the oculomotor complex in the
mesencephalon. Parasympathetic neurons in this nucleus project to the eye via CN III
and synapse onto postganglionic neurons in the ciliary ganglion

o

T
he
Superior salivatory nucleus

>> in the ro
stral medulla.



Parasympathetic neurons in this nucleus project to the pterygopalatine via CN
VII >> supply the lacrimal glands.



Another branch of the facial nerve carries preganglionic fibers to the
submandibular ganglion >> supply submandibular and subl
ingual glands



T
he
Inferior salivatory nucleus
, and the rostral part of the
nucleus ambiguus

in
the rostral medulla contain parasympathetic neurons that project via CN IX to
the otic ganglion >> supply to the parotid gland

-

Cranial Nerve X: Cell bodies are f
ound in the medulla within the
nucleus ambiguus

and the
dorsal motor nucleus of the vagus >> supplies parasympathetic innervation to all the viscera of
the thorax and abdomen, including the GI tract between the pharynx and distal end of the
colon.

-

Post
ganglions are not myelinated (gray rami)

-

Slide 12

Parasympathetic vs. Sympathetic

-

Almost all organs have dual innervation from sympathetic and parasympathetic.

-

Know eye, heart, and digestion

Parasympathetic “rest and digest”

Sympathetic “fight or flight”

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-

Internal organs are densely innervated by visceral afferents. These

receptors
monitors either
nociceptive (painful) input
or
sensitive to mechanical and chemical stimuli
(stretch of the heart,
blood vessels, and hollow viscera, and changes in PCO
2
, PO
2
, pH, blood glucose, temperature of
skin and internal organs)

-

Most of t
he
visceral nociceptive fibers travel with sympathetic nerves
, while
axons from
physiological receptors travel with parasympathetic fibers
.

-

The visceral afferent axons are mainly concentrated in the vagus nerve, which carries non
-
nociceptive afferent inpu
t from the viscera of thorax and abdomen to the CNS.

o

The cell bodies of vagal afferents are located in the nodose ganglion of medulla.

-

The visceral pain input is mapped 'viscero
-
topically' at the level of the spinal cord because most
visceral nociceptive

fibers travel with the sympathetic fibers and enter the spinal cord along
with a spinal nerve.

-

This mapping is also present in the brain stem, but not at the level of cerebral cortex.

o

Awareness of visceral pain is not localized to a specific organ but i
s instead
referred

to
the dermatome that is innervated by the same spinal nerve.

-

The pain fibers travel with the sympathetic nerve because sympathetic may need to be
activated

-

Mechanoreceptors (pH, pCO2, etc) stay with parasympathetic because more closely

related to
what it does

-

Referred pain


once nocioceptive fibers are carried up to the spinal cord and the mapping
information is not very well maintained

The Myenteric or Auerbach’s Plexus

-

The myenteric plexus lies between the external longitudinal and t
he deeper circular smooth
-
muscle layers.

o

It is involved in the control of motility

-

Submucosal (Meissner’s) plexus lies between the circular muscle and the most internal layer of
smooth muscle, the muscularis mucosae.

o

It is involved in the control of ion
and fluid transport

-

When circular muscles are contracting they try to make a churn; after done churning need
longitudinal to move it down the system

-

A
lkylasia


congenital problem there is a dysfunction of ganglion cells in the myenteric plexus
and can have

an accumulation of stool

Major Neurotransmitters of the ANS

-

Adrenal medulla
plays a role as a ganglion;
ACh comes into the medulla
ganglia cells and then
medulla secretes
epinephrine from
chromaphyn cells

-

Slide 19

-

Look at B and C; can
never make epinep
hrine if
you don’t have adrenal
medulla/chromafin cells

-

Norepi


only can be
released into synaptic cleft

-

Epi


released into
the bloodstream for more
global distribution



Cholinergic Neurotransmission

-

Release ACh from pre
-
synaptic

-

Vesamicol stops in
side t
he pre
-
synaptic terminal

-

A
cetylcholinesterase breaks down ACh to choline and acetate to be recycled

-

Muscarinic and Nicotinic receptors on the other side

-

Slide 21

Adrenergic Neurotransmission

-

Release norepi to the alpha and beta receptors

-

T
he main pathway for the norepi reuse is by uptake on the pre
-
synaptic side to make a norepi
pool, which is maintained by MAO enzymes.

-

The ones within the synaptic cleft will be taken care of by COMT

-

Slide 23

Cholinergic Muscarinic Receptors


-

Not many di
fferences;

-

M2 is in the heart; only parasympathetic has anything to do with accommodation; works on
heart rate not contraction strength; sweat glands
controlled by sympathetic





Adrenergic Receptors


-

Beta 1 receptors mostly seen in the heart; you incre
ase the heart rate and increase the number
of action potentials also vasoconstricting blood vessels to bring more blood to the heart (more
pre
-
load)

-

Beta 2 mostly not innervated


use epinephrine because it goes through the blood

-

Alpha 1

> radial (dilator)
muscle causes mydriasis (wider pupil)

G
-
protein Coupled Secondary Messengers in Cholinergic Receptors

M
1

and M
3

G
q

coupled

↑ phospholipase C →↑ IP
3
, DAG, Ca
2+

M
2

G
i

coupled

↓ adenylyl cyclase → ↓ cAMP





G
-
pr
otein Coupled Secondary Messengers in
Adrenergic Receptors

α
1

G
q

coupled

↑ phospholipase C →↑ IP
3
, DAG, Ca
2+

α
2

G
i

coupled

↓ adenylyl cyclase → ↓ cAMP

β
1
β
2
D
1

G
s

coupled



adenylyl cyclase →


cAMP

-

Nicotinic receptors are not G
-
protein coupled. Thus, no second messenger is involved.

-

If calcium increases on the post
-
synaptic side then we are activating and increasing smooth
muscle contraction

-

Alpha 2 usually on pre
-
synaptic side and they are usually inhibitory

-

Alpha 1 stimulates/activates post synaptic side but with a different mechani
sm

-

α
1 receptors:

o

V
ascular smooth muscle, on GI and bladder sphincters, and radial muscle of the eye

o

C
ause excitation (contraction)

o

Gq IP3

-

α
2 receptors

o

P
resynaptic nerve terminals, platelets, fat cells, walls of GI tract

o

C
ause inhibition (dilatation)

o

I
nhibition of adenylate cyclase and decrease in cAMP

-

β
1 receptors

o

SA node, AV node, ventricular muscle of heart

o

produce excitation (increa
s
es

heart rate, contactility, increased conduction

velocity

o

S
timulation of adenylate cyclase and increase in cAMP

-

β
2 receptors

o

vascular smooth muscle of skeletal muscle, bronc
hioles, walls of GI tract and
bladder

o

P
roduce relaxation (dilation of vascular sm
ooth muscle and bronchioles,
relaxation of
bladder wall)

o

S
timulation of adenylate cyclase and increase in cAMP


-

Learn the agonist column

on slide 29


some respond better to epi better than norepi;
important because depending on level of epi you have the response you get from the tissue will
be different

Sympathetic and Parasympathetic Stimulation of t
he Eye

-

Muscarinic stimulation:

o


Miosis

o

A
ccomodation (near vision)

-

Muscarinic antagonism

o

Mydriasis

o

Accom
m
odation for far vision leading to cycloplegia (paralysis of accomodation)

-

α
1 stimulation:

o

Mydriasis

o

No cycloplegia

-

Both cause constriction, but
of different
muscles and arrangements

-

Parasympathetic


Muscles run from center
to outside and when constricted they make
the pupil smaller

-

Sympathetic


radial muscles go from the
midline to the sides, and when constricted
they get shorter and cause pupil t
o get larger (alpha 1 receptor)

-

Remember type of receptor
-

has nothing to do with accommodation

-

Looking at the ciliary muscles with suspensory ligaments all around the lens holding it in place

-

Accommodation
-

due to ciliary muscles

-

Parasympathetic causes r
elaxation and lens become rounded (shape maintained by
parasympathetic)

-

Sympathetic causes lens to tighten and become flat

-

Slide 31

Non
-
classic Neurotransmitters

-

Nitric oxide and ATP


usually released with norepi;

-

I
f you follow them ATP will go to its re
ceptor and allow come calcium to come in from outside
(muscle contraction), which opens up more calcium channels and starts peak contract
ions of the
smooth muscle

-

Then norepi will come and start

worki
ng with G
-
proteins to release more

calcium and end up
wi
th maintain
in
g more and prolonged smooth muscle contraction

Cotransmission with ATP, norepinephrine, and neuropeptide Y in the ANS

-

ATP binds to their receptor and allows some calcium to come inside.

-

Increase in calcium opens more channels, norepinephrine

comes in and releases more calcium
promoting longer smoother contraction

-

Slide 33

Action of Nitric Oxide (NO) in the ANS

-

With nitric oxide we are trying t
o dilate places (venous system)

-

L
-
arginine with NOS (nitric oxide synthase) will make nitric oxide

o


Doesn’t need a receptor because it is a gaseous molecule and will seep from one cell to
another

-

Always goes to cGMP and activates it and cause relaxation.

-

Slide 34

CNS Control of the Viscera

-

In response to fear, exercise, or other types of stress, the s
ympathetic division produces a
massive and coordinated output to all end organs simultaneously (fight
-
or
-
flight), whereas
parasympathetic output ceases

-

This sympathetic response includes increases in heart rate, cardiac contractility, blood pressure,
and
ventilation of the lungs; bronchial dilatation, sweating, piloerection, release of glucose into
the blood, and decreased GI activity

-

The hypothalamus is the most important brain region for coordinating autonomic output.

-

The hypothalamus projects to the pa
rabrachial nucleus, medullary raphe, NTS (nucleus tractus
solitarius), central gray matter, locus coeruleus, dorsal motor nucleus of the vagus, nucleus
ambiguous, and intermediolateral cell column of the spinal cord.

-

The hypothalamus plays a dominant role

in the integration of higher cortical and limbic systems
with autonomic control.

-

feeding, thermoregulation, circadian rhythms, water balance, emotions, sexual drive,
reproduction, motivation

-

Sympathetic and parasympathetic are not one way, and can get s
ome control from
hypothalamus/hippocampus as well

Hierarchal Reflex Loops in the ANS

-

All of the primitive things have to be taken care of by the ANS and hypothalamus first before
upper neo
-
cortex can begin

-

Pictures on slide 37

Horner Syndrome

-

The combinati
on of unilateral
ptosis

(drooping eyelid),
miosis

(small pupil), and
anhidrosis

(lack
of sweating).

-

Sympathetic neurons innervate the smooth muscle that elevates the eyelid, the pupillary dilator
muscle, and the sweat glands of the face. Horner syndrome r
esults from loss of the normal
sympathetic innervation on one side of the face.

Lecture 4
-

Sensory Receptors and Somatosensory Pathways

Somatic Senses

-

T
he
mechanoreceptive somatic senses
, which include both
tactile

and
position

sensations that
are stimulated by mechanical displacement of some tissue of the body

-

T
he
thermoreceptive senses
, which detect heat and cold

-

T
he
pain sense
, which is activated by any factor that damages the tissues.

-

2 major somato
-
sensory pathways that di
ffer through their anatomy in terms of how they are
carried through the spinal cord and carry different sensations

Receptors in the Skin

-

Meissner’s


fine communication from the finger tips

-

Pacini’s corpuscle


mechanoreceptors

-

Ruffini’s


try to get any changes from the top

-

Slide 5


Sensory Neuron Fiber Types

-

Table 7.2 on slide 6

-

Golgi tendon
-

attaches muscle to the bone and measures the tension and force generated (A1B)

-

Muscle spindle
-
specialized sensory fibers in the muscle fiber and me
asures muscle length
(stretch); depending on how the sensory parts come and wrap this area (type I or II)

-

A
-
alpha 1 is the muscle spindle as well as A type II

-

AB type 1 is the golgi tendon organ

Receptor Potential of the Pacinian Corpuscle

-

F
irst node of R
anvier, lies inside the capsule of the pacinian corpuscle

-

If you give a brief stimulus and then take it away, the Pacinian corpuscle will also fire quickly and
go away

-

If you keep the response it adapts quickly and fires initially but then stops and again

when the
stimulus is removed they alert body that it isn’t there anymore

-

Slide 8

Relationship Between Receptor Potential and Action Potentials

-

The more the receptor potential rises above the threshold level, the greater becomes the
action
potential freque
ncy
.

-

Amplitude cannot change but can change the frequency and release more neurotransmitters to
make a stronger stimulus for the upper centers

Adaptation of Receptors

-

All sensory receptors
adapt

either partially or completely to any constant stimulus afte
r a period
of time

-

Red
-

slowly adapting; black
-

quickly adapting

-

Slide 11

Cold and Warmth Receptors

-

Warmth receptors

begin firing above about 30°C and increase their firing rate until 44°C to 46°C

-


beyond 46°C, the rate falls off steeply and a sensation of pain begins

-


Cold receptors

steady discharge rate increases as the temperature falls to 24°C to 28°C

-


Below 10°C, firing ceases and cold becomes a very effective local anesthetic

-

Anything below 10

you are basically numb to; you know it is there but don’t interpret cold

Pacinian and Meissner’s Corpuscles

-

Black dots indicate an area of maximal sensitivity of a single Pacini’s corpuscle

-


The green area is the receptive field of a corpuscle

-

Homonculus


big hands, big lips, big head because that is where the sensory receptors are
concentrated

-

Pacinian


Have one dot that carries information and sensation for whole green area.
Meissner’s can only do black dot and will be more sensitive to exact location
and better 2
-
point
discrimination because Pacinian cannot fully separate information

-

Slide 13

Inhibitory Circutiry for the Two
-
Point Discrimination

-

Have to inhibit A and C to be able to pinpoint where the pin is located

-

Slide 14

Peripheral Sensitization

-

Fo
llowing a painful stimulus (cuts, scrapes, bruises), stimuli in the area of the injury that would
ordinarily be perceived as slightly painful are perceived significantly more

-

Results from the interaction of nociceptors with the “inflammatory soup” of subst
ances released
when tissue is damaged

o

Arachidonic acid, lipid metabolites, bradykinin, histamine, serotonin, prostaglandins,
nerve growth factor

-

Sunburn example
-

t
-
shirt hurts after sunburn when it normally wouldn’t


Sensory Pathways

-

Almost all sensory in
formation from the somatic segments of the body enters the spinal cord
through the dorsal roots of the spinal nerves.

-

From the entry point into the cord and then to the brain the sensory signals are carried through
one of two alternative sensory pathways:


o

T
he
dorsal column
-
medial lemniscal pathway



Proprioception/fine touch

o

T
he
anterolateral pathway




Pain and temperature

-

These two systems come back together partiall
y at the level of the thalamus

-

Slide 18

-

Way they go from the spina
l cord are completely
different


-

A
ll of the sensory information has to go through a thalamic nucleus first to go to proper cortex

-

Dorsal column


all come in; first
-
order neuron and will ascend the spinal cord and when
reaches the brain stem; at the brain stem there are speciali
zed nuclei which take information to
the opposite side of the brain


to the thalamus and finally somatosensory cortex

-

AL


afferents from dorsal horn into spinal cord where is crosses to the opposite side


brain
stem


thalamus


cortex

The Neurons

-

The
first
-
order neuron

in the somatosensory pathway is the primary afferent neuron. Primary
afferent neurons have their cell bodies in dorsal root or cranial ganglia, and their axons synapse
on somatosensory receptor cells

o

The signal is transduced by the rece
ptor and transmitted to the CNS by the primary
afferent neuron.

-

The second
-
order neuron

is located in the spinal cord (anterolateral system) or in the brain
stem (dorsal column system). The second
-
order neurons receive information from first
-
order
neurons

and transmit that information to the thalamus. Axons of the second
-
order neurons
cross the midline,

either in the spinal cord or in the brain stem, and ascend to the thalamus.

o

This decussation means that somatosensory information from one side of the bod
y is
received in the contralateral thalamus.

-

The
third
-
order neuron

is located in one of the somatosensory nuclei of the thalamus. The
thalamus has a somatotopic arrangement of somatosensory information.

-

The
fourth
-
order neuron

is located in the somatosensory cortex. Higher
-
order neurons in the
somatosensory cortex and other associative cortical areas integrate complex information.

-

The somatosensory cortex has a somatotopic representation, or "map," similar to that in the
thala
mus (
somatosensory homunculus
).

Somatosensory Cortex

-

Information first processed in the frontal lobe and then moves backward

-

Somatosensory
-

hands have so many receptors and fibers that they have a b
igger area of the
cortex








Layers of the Neocortex

-

Table 2.3 on slide 25

-

Within the layers the neurons are also arranged in columns

-

Each column serves a specific sensory modality (i.e., stretch, pressure, touch)

-

IV
-

get information from thalamus

-

VI
-

sends information to the thalamus

Dorsal Column System

-

Contains large myelinated nerve fibers for fast transmission (30
-
110 m/sec).

-

High degree of spatial orientation maintained throughout the tract.

-

Transmits information rapidly and with a high degree of
spatial fidelity (i.e., discrete types of
mechanoreceptor information).

-

Touch, vibration, position, fine pressure

Dorsal Column
-
Medial Lemniscal System

-

Goes to VPL of Thalamus

-

Touch sensations requiring a high degree of localization of the stimulus

-

Touch
sensations requiring transmission of fine gradations of intensity

-

Phasic sensations, such as vibratory sensations

-

Sensations that signal movement against the skin

-

Position sensations from the joints

-

Pressure sensations having to do with fine degrees of

judgment of pressure intensity

-

Slide 29

Anterolateral System

-

Smaller myelinated and unmyelinated fibers for slow transmission (0.5
-
40 m/sec)

-

Low degree of spatial orientation

-

Transmits a broad spectrum of modalities

-

Pain, thermal sensations, crude touch
and pressure, tickle and itch, sexual sensations.

-

Low degree of spatial orientation and mapping not as precise as the posterior column

-

Tells brain if there is pain and if endorphins need to be released

-

Slide 32

Somatotopic Organization of the Sensory
Pathways

-

Know the order of anterolateral and posterior columns on slide 33

Dissociated Sensory Loss

-

Following a spinal cord hemisection at the 10
th

thorasic level on the left side

-

This pattern, together with motor weakness on the same side as the lesion is

also referred as

Brown
-
Sequard Syndrome


-

Lesion only happens to one side of the spinal cord

-

One or two levels above or below will have loss of sensation because of swelling, etc

-

Cut everything on the same side

-

Same side proprioception/touch is lost

-

Oppo
site side pain and temperature is lost

-

Slide 34

Review pictures on slides 35 and 36

Lecture 5
-

Motor Functions of the Spinal Cord

Motor Organization of the Spinal Cord

-

Sensory fibers enter the cord and are transmitted to higher centers, or they synapse lo
cally to
elicit motor reflexes

-

Motor neurons are located in the anterior portion of the cord.

o

M
otor neurons are 50
-

100 % bigger than other neurons

-

All of the motor neurons are in the anterior horn on the spinal cord (alpha and gamma types)

Anterior Motor

Neurons

-

Alpha motor neurons

o

G
ive rise to large type A alpha fibers (~14 microns).

o

S
timulation can excite 3
-

100
extrafusal

muscle fibers collectively called a motor unit

-

Gamma motor neurons

o

G
ive rise to smaller type A gamma fibers (~5 microns)

o

G
o to small, special skeletal muscle fibers called
intrafusal fibers


-

Start
ing

from the cortex and com
ing

down to the spinal cord are the UMN
-

lots of
flexion/contraction

-

LMN start in anterior horn and go to muscle
-

flaccid

Interneurons and Propriospinal Fi
bers

-

Interneurons

o

30 times as many as anterior motor neurons

o

S
mall and very excitable

o

C
omprise the neural circuitry for the motor reflexes

-

Renshaw Cell Inhibitory System
:
immediately after the anterior motor neuron axon leaves the
body of the neuron, coll
ateral branches from the axon pass to adjacent Renshaw cells. These are
inhibitory cells

that transmit inhibitory signals to the surrounding motor neurons

-

Propriospinal fibers

o

T
ravel up and down the cord for 1
-

2 segments

o

P
rovide pathways for
multisegmental reflexes

-

Communicate between motor and sensory and work as inhibitory

-

Reflexes only go through spinal cord (why they are so quick); inhibition has to go through spinal
cord

-

Anterior motor neurons leave and pass collateral braches to Renshaw
cells which sends out
inhibitory message

Sensory Receptors of the Muscle

-

Muscle Spindle

o

S
ense muscle length and change in length

-

Golgi Tendon Organ

o

S
ense tendon tension and change in tension

o

T
oo much force generated and about to tear then golgi tendon will

relax the muscles

-

The signals from these two receptors are almost entirely for the purpose of intrinsic muscle
control

Golgi Tendon Organ and Muscle Spindle Fibers

-

Parallel to muscle fibers


muscle spindles

-

Alpha motor neurons go to the extra
-
fusal fiber
s and really generate the force from the muscle

-

Gamma motor neurons go and wrap around the muscle spindles intrafusal fibers

-

Two types of wrapping: come and touch and wrap one area vs. wrapping both areas (class I and
II)

-

Picture on slide 7

Muscle Proprioc
eptors

-

Primary fiber is slightly larger and thicker

-

Each intrafusal muscle fiber is a very small skeletal muscle fiber. However, the central region of
each of these fibers has few or no actin and myosin filaments >>> this central portion does not
contract
when the ends do, it functions as a sensory receptor

-

Start contraction and extrafusal fibers begin to get smaller, and gamma neurons need to
contract simultaneously to keep muscle happy (alpha
-
gamma coactivation)

-

1B goes to golgi tendon organ

-

Picture on
slides 8 and 9

-

Primary Ending (
annulospiral ending):
In the center of the receptor area, a large sensory nerve
fiber encircles the central portion of each intrafusal fiber,

o

T
ype Ia fiber, 17

m, signal conduction velocity is 70 to 120 m/sec

-

Secondary End
ing:
type II fibers (8

m) innervate the receptor region on one or both sides of
the primary ending

o

S
preads like branches on a bush.

-

Group II secondary afferent in the picture

-

Important for prolonged continued muscle contraction and stretch reflexes

-

Slide

11

Physiologic Function of the Muscle Spindle

-

The simplest manifestation of muscle spindle function is the
muscle stretch reflex
.


-

Whenever a muscle is stretched
suddenly
, excitation of the spindles causes reflex contraction of
the large skeletal muscle fibers of the stretched muscle and also of closely allied synergistic
muscles.

-

Muscles don’t like to be suddenly stretched. They will react with a contraction

Co
-
activati
on of Alpha and Gamma Motor Neurons

-

It keeps the length of the receptor portion of the muscle spindle from changing during the
course of the whole muscle contraction.

o

Therefore, coactivation keeps the muscle spindle reflex from opposing the muscle
contract
ion

-

Also, it maintains the proper damping function of the muscle spindle, regardless of any change
in muscle length.

-

If the sensory parts aren’t working properly then extrafusal fibers start contracting and nothing
comes to intrafusal fibers to get shorte
r and they still keep the sensory parts in the same length
then they will cease postpone action potentials/firing rate will decrease

-

But activating both gamma and alpha will keep sensory fibers happy and they can have a
constant firing rate of action poten
tials for constant contraction

-

Slide 14

Damping Mechanism in Smoothing Muscle Contraction

-

If the muscle spindle apparatus is not functioning properly, the muscle contraction is jerky
during the course of such a signal

-

Won’t have nice smooth contraction
-

d
on’t get enough sensory information back so muscle
begins to relax and then contracts against

Role of the Muscle Spindle in Voluntary Motor Activity

-

31 % of all the motor nerve fibers to the muscle are the small type A gamma efferent fibers

o

Whenever alpha

motor neurons are stimulated by upper centers,
-
in most instances
-

the
gamma motor neurons are stimulated simultaneously >>>
coactivation

of the alpha and
gamma motor neurons.

-

This causes both the extrafusal skeletal muscle fibers and the muscle spindle
intrafusal muscle
fibers to contract at the same time.

Neuronal Circuitry of the Stretch Reflex

-

Monosynaptic pathway

allows a reflex signal to return with the shortest possible time delay
back to the muscle after excitation of the spindle.

-

The reflex fun
ctions to oppose sudden changes in muscle length


-

C
omes from and goes to the same skeletal muscle

-

This pathway will work to oppose sudden changes in the muscle length

-

Stimulus comes and sensory information comes into the same segment

Clinical Application
of the Stretch Reflex

-

The purpose is to determine how much background excitation, or "tone," the brain is sending to
the spinal cord

-

Index of the facilitation of the gamma efferents.

-

Cortical lesions usually increase muscle stretch reflexes.

-

“Knee jerk re
flex”

Spinal Reflex Circuits

-

When a skeletal muscle is abruptly stretched, often a rapid, reflexive contraction of the same
muscle occurs

o

The contraction increases muscle tension and opposes the stretch

-

This stretch reflex is particularly strong in physiol
ogical extensor muscles and is also called the
myotatic reflex


-

Knee Jerk
: A light tap on the patellar tendon deflects the tendon, which then pulls on and briefly
stretches the quadriceps femoris muscle

o

A reflexive contraction of the quadriceps quickly fol
lows

Knee
-
jerk (myotatic) Reflex

-

Passively stretching a skeletal muscle causes a reflexive contraction of that same muscle and
relaxation of the antagonist muscles

-

One is activated and the other is inhibited

-

Slide 22

-

The stretch reflex depends on the nervo
us system and requires sensory feedback from the
muscle

-

Cutting the dorsal (sensory) roots to the lumbar spinal cord abolishes the stretch reflex in the
quadriceps muscle

-

Reciprocal innervation
: As the knee
-
jerk reflex causes contraction of the quadriceps
muscle, it
simultaneously causes relaxation of its antagonist, the semitendinosus muscle

-

Branches of the group Ia sensory axons excite specific interneurons that inhibit the
α

motor
neurons of the antagonists

-

Relaxes semitendinosus muscle

Muscle Spindle
Function in the Stretch Reflex

-

Pictures on slides 24 and 25

-

Can always inhibit them through the upper centers (example nurse giving a shot to a child vs.
adult); not affect them just in the spinal cord

Inverse Myotatic (Golgi Tendon) Reflex

-

Golgi tendon
organ
s are aligned in series with the muscle and exquisitely sensitive to the
tension

within a tendon

o

R
espond to the force generated by the muscle rather than to muscle length

-

The group Ib sensory axons of the tendon organs excite both excitatory and inhi
bitory
interneurons within the spinal cord

o

This circuit inhibits the muscle in which tension has increased and excites the
antagonistic muscle >>> opposite of the stretch reflex

-

Functions to equalize force among muscle fibers & prevents the development of
too much
tension on the muscle.

-

Does opposite of the stretch reflex

Golgi Tendon Reflex

-

Cause an active shortening and not a stretch on the muscle and is sensed by golgi tendon which
sends fibers upwards and the inhibition comes to the same muscle and the

excitation goes to
the opposite muscle

-

Picture on slide 27

Inhibitory Nature of the Tendon Reflex

-

When tension on the muscle and, therefore, on the tendon becomes extreme, the inhibitory
effect from the tendon organ can be so great that it leads to a sudd
en reaction in the spinal cord
that causes instant relaxation of the entire muscle;
lengthening reaction

o

I
t is a protective mechanism to prevent tearing of the muscle or avulsion of the tendon
from its attachments to the bone.

Noxious Stimuli and Flexor R
eflex

-

Painful stimulus to the right foot elicits a reflexive flexion of the right knee and an extension of
the left knee

o


The stimulus for the reflex come from fast pain afferent neurons in the skin, primarily
the group A
δ

axons

-

Unlike simple stretch refl
exes, flexor reflexes coordinate the movement of entire limbs and even
pair of limbs

-

Example
-

Walking on a beach and step on something sticky

need to pull

body weight from one
side and need to put it on the other side

-

Not just one portion, but goes to oppo
site side and does the opposite effect on other leg. Multi
-
unit reflex

-

Slide 30/31

Movement: Coordination of Several Muscle Groups

-

Reflexive Movement

o

Spinal integration

o

Input to brain

-

Postural reflexes

o

Cerebellum integration

o

Maintains balance

o

Input to
cortex

-

Reflexive movements go through spinal cord, but many other centers will also be affected

-

Cerebellum and balance in flexor reflex

Lecture 6
-

Cortical and Brainstem Control of Motor Function

The Motor Control Centers

-

In the Brainstem:

o

Vestibular nucle
ar complex
---

o

Reticular formation
---




Both
effect the body position

o

Red nucleus
---
controls movement of the arms

o

Superior colliculus
---
initiate orienting movements of the head and eyes

-

Motor and Premotor Areas of the frontal lobe:

o

Responsi
ble for the planning and precise control of complex sequences of voluntary
movements

-

Motor and pre
-
motor give the orders and the sequences of motor fine tuning and when certain
muscles parts will start getting into this action and then in which sequence th
ey will get
activated

-

From primary motor cortex start corticospinal pathway; once these fibers come through the
internal capsule they come to the medulla to the pyramidal decussation and cross over and
locate themselves in lateral part of the spinal cord

L
ateral Motor Systems

-

Lateral tract


going to see more pronounced at the enlargement of the spinal cord

-

Slide 5


Rubrospinal Tract

-

Start from the red nucleus; ends at the cervical level, function uncertain in humans because it
ends in the cervical cord
level

-

Slide 6


Medial Motor Systems

-

There is no crossing over until it reaches the segment it wants to innervate and bilaterally
innervates the lower motor neuron and controls bilateral axial and girdle muscles; this ends
within cervical (maybe T1/T2)

-

Slide 7


Vestibulospinal Tract

-

No decussation; medial has to do with positioning head and neck and the lateral one has to do
with balance (communicates with cerebellum)

-

Slide 8


Reticulospinal and Tectospinal Tracts

-

Tectospinal


uncertain in humans start
s in superior colliculus; dorsal tegmental decussation
and again ends at cervical cord because deals with head and eye movements

-

Retriculospinal


no decussation, goes entire length of the spinal cord, related to gait
movements/automatic posture

-

Slide 9



Ventral Horn

-

Lower motor neurons in the ventral horn of the spinal cord are organized in a somatotopic
fashion

-

The most medial part of the ventral horn contains lower motor neuron pools that innervate axial
muscles or proximal muscles of the limbs, wher
eas the more lateral parts contain neurons to
innervate the distal muscles of the limbs

**Know the tables on slide 14
-
16 especially the muscles the cranial nerves go to**

Controlling Movements of the Eye

-

CN VI abducts the eye laterally in the horizontal di
rection

-

CN IV rotates the top of the eye medially and move it downward

-

CN III subserves all other eye movements

o

CN III also carries parasympathetics to the pupillary constrictor and to the ciliary muscle
of the lens


Cranial Nerve Parasympathetic Pathw
ays

-

CN III
: to pupil constrictor and ciliary muscles for near vision

-

CN VII
: to lacrimal glands, and to submaxillary, submandibular, and all other salivary glands
except parotid

-

CN IX
: to parotid gland

-

CN X
: to heart, lungs, and digestive tract down to the

splenic flexure

Trigeminal Nerve (CN V)

-

The upper motor neuron control reaching the trigeminal motor nucleus is bilateral, so unilateral
lesions in the motor cortex or corticobulbar tract usually cause no deficit in jaw movement

-

The branchial motor root
supplies the muscles of mastication (masseter, temporalis, medial and
lateral pterygoid, along with several smaller ones)

-

Corticospinal motor pathway is
the UMN coming down and reaching

to anterior motor neuron
(LMN); all cranial nerves have these upper co
rticobulbar fibers coming to them as UMNs
anything we see coming from the brainstem or the originating nuclei for the cranial nerves going
to the target organ are the LMNs

-

Picture on slide 19

Facial Nerve (CN VII)

-

The main nerve trunk carries the branchial

motor fibers controlling facial expression, while
smaller branch (nervus intermedius) carries fibers for the parasympathetic (tears and salivation),
visceral sensory (taste) and general somatosensory functions

-

Slide 20

Upper vs. Lower Motor Neuron Facial

Weakness

-

Upper motor neurons in the face area of the primary motor cortex control lower motor neurons
in the contralateral facial nucleus of the pons

-

Also, for the superior portions of the face, projections descend from both the ipsilateral and
contrala
teral motor cortex

-

The lower motor neurons supplying the forehead and part of the orbicularis oculi receive upper
motor neuron inputs from bilateral motor cortices

-

As a result, unilateral upper motor neuron lesions tend to spare the forehead and cause only

mild contralateral orbicularis oculi weakness

-

Forehead has dual UMN innervation so provides some sensation to the top of the face because
lesion
A
only affects one side

-

Because LMN is provided only on
one
fiber if lesion B occurs you will lose sensation t
o the whole
face (ipsilateral)

-

Lower motor neuron lesions, in contrast, affect the entire half of the face and do not spare the
forehead

-

Slide 21

Glossopharyngeal Nerve (CN IX)

-

Stylopharyngeus elevates the pharynx during talking and swallowing, and
contributes (with CN
X) to the gag reflex

-

Parasympathetic preganglionic fibers arise from the inferior salivatory nucleus to provide to the
parotid gland

-

Slide 25

Vagus Nerve (CN X)

-

Parasympathetic innervation to the heart, lungs and digestive tract (to
the splenic flexure)

-

Postganglionic neurons are located in terminal ganglia

-

The branchial motor part controls nearly all pharyngeal muscles and the muscles of the larynx

-

Recurrent laryngeal nerve loops back upward from the thorasic cavity to control all in
trinsic
laryngeal muscles, except cricothyroid, which is innervated by superior laryngeal nerve

-

Slide 26

Spinal Accessory Nerve (CN XI)

-

The nucleus protrudes laterally between the dorsal and ventral horns of the spinal cord central
gray matter

-

CN XI suppli
es the sternomastoid and upper portions of the trapezius muscle

-

The sternomastoid muscle turns the head toward the
opposite side
, and trapezius is involved in
elevating the shoulder

o

Lower motor neuron lesions of CN XI may cause some ipsilateral weakness of

shoulder
shrug or arm elevation, and weakness of head turning
away

from the lesion

Central Pattern Generators

-

An important feature of motor control is called
Motor program


o

A set of structured muscle commands that are determined by the nervous system
befo
re a movement begins is sent to the muscles with the appropriate timing so that a
sequence of movements occurs without any need for sensory feedback

-

The brain or spinal cord can command a variety of voluntary and automatic movements, such as
walking and br
eathing, even in the complete absence of sensory feedback from the periphery

-

Central Pattern Generators

are circuits that underlie many of the rhythmic motor activities

-

Have to do with motor programming


any type of rhythmic motor activity that we learn an
d
keep in memory and keep doing it all of these neurons can activate themselves without any
outside information coming in and activating them (sensory or motor); activities such as
walking, breathing, swimming, etc

Rhythmic Activity

-

Rhythmic behavior incl