ORGANIZATION OF
THE NERVOUS
SYSTEM
Outline
2
Introduction to the structure/function of
central nervous system (CNS)
Protection of CNS
Introduction to peripheral nervous
system (covered in more detail later)
Microanatomy: neurons
Divisions of the Nervous
3
System
Enteric nervous system
http://www.nlm.nih.gov/medlineplus/ency/images/ency/fullsize/8679.jpg
Divisions of the Nervous
4
System
http://faculty.washington.edu/chudler/nsdivide.html
CNS: Spinal cord
5
Functions
1. Conducts afferent
stimuli from
sensory receptors
to the brain
2. Conducts efferent
stimuli from brain
to
effectors/muscles
3. Site of reflex
integration and
houses
certain central
CNS: Spinal cord input/output
6
* *
Afferent fibre *
Efferent fibre *
*
* Part of the peripheral nervous Figure 4-8, B&L
CNS: Spinal cord tracts
7
Tract: collection of axons that ascend/descend 3
spinal cord with a specific function
1. dorsal columns: ascending tracts that
transmits tactile and proprioceptive
info
2. spinothalamic tract: ascending tract
that
transmits info about pain, temp. and Silverthorn Figure 9-7
CNS: Brain, three basic units
9
Illustrative guide to the
basic units of the brain:
Forebrain/midbrain/
hindbrain
CNS: Brain, five regions
10
Regions grouped and named as they
develop in the embryo
Figure 10-6, B&B http://www.ruf.rice.edu/~lngbrain/cglidden/middlelabnoline!!yes2use2.jpg
Telencephalon: Basal Ganglia
15
Functions
1. Motor control;
connections with motor
cortex and thalamus
2. Regulate initiation and
termination of
movements
3. Some role in attention,
memory and planning
Telencephalon: Amygdala &
16
Hippocampus
Amygdala functions
1. Part of the limbic system
2. Associated with pleasure, fear,
addiction
3. Important in forming and
storing
memories of emotional events
Hippocampus functions
4. Part of the limbic system
5. Important in formation of
memories, including spatial
and navigation memories
6. Damage to hippocampus can
result in anterograde
amnesia
Forebrain part 2: Diencephalon
17
includes the thalamus and Thalamus functions
hypothalamus 1. Main integrating centre for
Telencephalon + diencephalon = sensory information
forebrain 2. Receives input from basal
ganglia and cerebellum
Hypothalamus functions
3. Main control centre for the
autonomic nervous
system
4. Close association with pituitary
gland, important functions in
the endocrine system
(hormone release)
5. Contains nuclei important in
regulation of circadian clock,
Midbrain: Mesencephalon
18
Two divisions:
a) tectum
superior colliculi
contain nuclei for visual
reflexes
inferior colliculi
contain nuclei for auditory
reflexes
b) tegmentum
substantia nigra
Release dopamine to basal
ganglia
red nucleus
Connections with cerebellum
for coordination of movement
Hinbrain: Myelencephalon
19
Two divisions:
a) myelencephalon
medulla oblongata
Contains ascending
and descending
sensory and motor
tracts connecting the
cerebrum to the
spinal cord
Most spinal cord tracts
cross over in the
pyramids
Contains nuclei that
regulate breathing,
blood pressure,
vomiting
Hinbrain: Metencephalon
20
b) metencephalon
pons
Contains pneumotaxic centre
which fine tunes breathing rate
Relays information between
cerebellum and cerebrum
cerebellum
Feedback center for execution
of motor movements
Controls posture and balance
reticular formation
Nuclei diffusely located through
the brainstem*
Regulates wakefulness and
muscle tone
*the term “brainstem” refers to the
CNS Protection
22
Against physical Against chemical Both
damage damage
Skull/vertebrae Blood brain barrier Cerebrospinal
-hard external - Tight junctions fluid
protection form physical -Shock
barrier across absorption
capillaries -Stable ionic
Meninges composition
-Pia mater
(innermost layer)
-Arachnoid
mater
Protection: Blood Brain Barrier
23
CNS blood vessels prevent
paracellular diffusion of
macromolecules and ions
Capillary endothelial cells in the
brain are connected by tight
junctions to form a physical
barrier, with contribution from
astrocytes, pericytes & neurons
Specialized transporters
required for movement of most
molecules
Small or lipophilic molecules and
gases can diffuse more easily
Caffeine, nicotine, heroin, CO2
Protection: Blood Brain Barrier
24
Only a few, small regions of the brain
are without a blood brain barrier
Creates problems for delivering
therapeutic drugs to the brain
Methods for drug targeting include:
Manufacturing low molecular
weight drugs
Tagging the drug with ligand to
assist in receptor mediated
transcellular transport
Injecting drug directly into
brain
matter
Protection: Cerebrospinal Fluid
25
Fluid synthesized by the
choroid plexuses in each
of the four ventricles
Fills ventricles and
subarachnoid space
Less protein than
plasma with similar
electrolyte composition
(but more Cl-, less
Ca2+ and K+)
Acts as a shock absorber
during impact
Removes waste,
regulates pH and
maintains ionic
homeostasis of neuronal
Peripheral Nervous System
27
all parts of nervous system outside the dura mater
includes sensory receptors, peripheral portions of
spinal and cranial nerves (including those of the
ANS), and sensory ganglia
sensory ganglia are aggregates of nerve cells located
outside the CNS
Autonomic Somatic
Parasympathet Sympathetic Sensory Motor
ic
Rest and Flight or fight Afferent Efferent neurons
digest neurons carrying
carrying information from
information from the CNS to
Microanatomy: Neurons and Glial
28
cells
Neurons Glial cells
Convey electrical signals regulate neuron environment
within CNS and PNS & form the myelin sheath
around neurons
a) Astrocytes: regulate
neuron environment
b) Oligodendrocytes: form
myelin sheath in CNS
c) Schwann cells: form
myelin sheath in PNS
d) Ependymal cells: line the
ventricles, synthesize CSF
e) Microglia: monocytes of
the brain
Classifications of Neurons
29
neurons can be classified by the
following characteristics:
B&B Figure 10-3
Classifications of Neurons
30
B&B Figure 10-3
Classifications of Neurons
31
B&B Figure 10-3
• The size of neuronal somas range widely from
0.005 mm to 0.1 mm in mammals.
• Collections of cell bodies (somas) give the greyish
appearance to the gray matter of the brain.
• The protoplasm of cell body contains peculiar angular
granules, which stain deeply with basic dyes, such as
methylene blue; these are known as Nissl’s granules.
• These granules disappear (chromatolysis) during fatigue or
after prolonged stimulation of the nerve fibers connected
with the cells. They are supposed to represent a store of
nervous energy, and in various mental diseases are
deficient or absent.
• Thought be involved in the synthesis
of to
neurotransmitters such as
acetylcholine.
• An axon is one of two types of protoplasmic protrusions that
extrude from the cell body of a neuron .
• Unlike dendrites axons are long, slender projection of a nerve
cell, or neuron, that conducts electrical impulses away from
the neuron's cell body or soma.
• Axons are distinguished from dendrites by
several features, including shape, length , and
function.
• The point where the axon arises from a cell body is termed
as axon hillock.
• Axoplasm is the cytoplasm within the axon of a neuron.
• The axolemma is the cell membrane surrounding an axon. It is
responsible for maintaining the membrane potential of the
neuron, and it contains ion channels through which ions can flow.
• In vertebrates, the axons of many neurons are sheathed
in myelin, which is formed by either of two types of glial
cells: Schwann cells ensheathing peripheral neurons and
oligodendrocytes insulating those of the central nervous
system
• The myelin sheath functions to:
– Protects the axon and electrically isolates it
– Increases the rate of Action Potential transmission (saltation)
• Along myelinated nerve fibers, gaps in the sheath
known as nodes of Ranvier occur at evenly-spaced
intervals.
• Terminally the Axon branch sparsely, forming collaterals.
Each collateral may split into telodendria which end in a
synaptic knob, which contains synaptic vesicles –
membranous bags of NTs.
• Axons make contact with other cells via the synaptic knob—
usually on dendrites of other neurons but sometimes
muscle or gland cells—at junctions called synapses.
• The region between the two connecting neurons is known as
the
synaptic gap or snaptic cleft or neural junction.
Interneuron-
– also called as relay neuron or local circuit neuron.
– connects afferent neurons and efferent neurons in neural
pathways.
BASED ON NEUROTRANSMITTER PRODUCTION
Cholinergic neurons —secreting acetylcholine
GABAergic neurons — secreting gamma aminobutyric acid.
Glutamatergic neuron — secreting glutamate
Dopaminergic neurons — secreting dopamine . Loss of dopamine
neurons in the substantia nigra has been linked to Parkinson's
disease
Serotonergic neurons — secreting serotonin. A lack of
serotonin at postsynaptic neurons has been linked to
depression.
BASED ON UNIQUE SHAPE AND FUNCTION
Betz cells – large motor neurons located within the fifth layer
of the grey matter in the primary motor cortex, M1.
Purkinje cells - some of the largest neurons in the
human brain, found within the Purkinje layer in the cerebellum.
Electrical conduction
RESTING MEMBRANE POTENTIAL
• The relatively static membrane potential of quiescent cells
is
called the resting membrane potential.
• Resting membrane potential of nerve cell = -70
mV
• Resting membrane potential is maintained by the
ionic distribution across the neuron cell membrane
• Ions involved mainly are the potassium and sodium ion.
• concentration gradients of Na+ & K+
– Na+ 10x greater outside
– K+ 30x greater inside
• At rest more K+ move out than Na+ move in.
• K+ ions diffuse out leave behind excess negative charge inside.
• Sodium-potassium pump
– Na+ out - K+ in (more Na+ out than K+ in)
– contributes to loss of (+).
THE ACTION
POTENTIAL :
• The action potential is generated by ion flux through
voltage
gated channels.
Neuroglia
Neuroglia - Cells that
provide metabolic support
and immune protection for
neurons.
Neuroglia outnumber
neurons by about 10:1 in
the CentralNeuroglia
System. Nervous do not
generate or conduct nerve
impulses. However, unlike
neurons, glial cells can
regenerate if injured
Astrocytes - Provide for the energy and other
metabolic needs of neurons as well as giving nervous
tissue structural support. When neurons of the brain or
the spinal cord are injured and destroyed, they are
replaced with scar tissue made up of astrocytes (a
process called gliosis).
Microglia - Phagocytic cells, similar to macrophages,
that perform a housekeeping function by removing
dead cellular material and bacteria from the CNS
Microglia - Phagocytic cells, similar
to macrophages, that perform a
housekeeping function by removing
dead cellular material and bacteria
from the CNS.
Ependymal Cells - Cells that line the
cerebral spinal fluid (CSF)
containing cavities of the brain - the
ventricles.
Oligodendrocytes - Cells
responsible for myelination of
axons within the Central
Nervous System.
The dendrites and axons of sensory neurons and motor
neurons that lie outside of the central nervous system in the
peripheral nervous system may be myelinated. Myelin
sheaths are formed by Schwann Cells. Schwann cells form
multiple layers of membrane around the neuron and insulate
it. In between the areas if myelin sheath, Nodes of Ranvier
or bare patches exist. The nerve impulse or action potential
will jump from node to node greatly increasing the speed of
nerve transmission. This node to node transmission, called
saltatory conduction, can produce transmission speeds of up
to 200 meters per second and explains the speed at which
we can react to potentially harmful stimuli.
Schwann cells - Glial cells that myelinate the axons of
peripheral nerves. These cells wrap their cytoplasm in a spiral
fashion around short segments of axons. Because the myelin
sheath is formed from numerous Schwann cells arranged
sequentially along the axon, there are gaps between adjacent
myelinating cells producing myelin-free areas of axon called
Nodes of Ranvier. These play an important role in nerve
impulse conduction.
Myelin
Myelination begins with the invagination of a single nerve axon into a
Schwann cell; a mesoaxon is then formed. As myelination proceeds, the
mesoaxon rotates around the axon enveloping it in concentric layers of
Schwann cell cytoplasm and plasma membrane.
NEURON
• It is the structural and the functional unit of
nervous system.
• The human nervous system contains
approximate 1012 neurons.
STRUCTURE OF NEURON
INTRODUCTION ABOUT
NERVE FIBER
• A nerve fiber is a thread like
extension of a nerve cell and
consists of an axon and
myelin sheath (if
present) in the nervous
system.
In peripheral nervous system it is formed by
schwann’s cell. While in case of central
nervous system it is formed by
oligodendroglia.
COMPOSITION
MYELIN SHEATH
LIPIDS(CHOLESTEROL,
PROTEINS LECITHIN &
SPHINGOMYELIN)
The places ,where myelin
sheath is absent
FACT are
MYELIN SHEATH
called nodeS of ranvier(2-
3µm) and these are
present once about 1-3
mm distance along the
myelin sheath.
About the myelinsheath
IT PREVENTS LEAKAGE OF IONS BY 5000 FOLDS.
IT INCREASES VELOCITY OF CONDUCTION BY 5-50 FOLDS DUE
TO SALTATORY CONDUCTION i.e. ABOUT 100 m/s IN CASE OF
MYELINATED NERVE FIBERS WHILE IN NONMYELINATED
IT IS ABOUT 0.25 m/s.
SALTATORY CONDUCTION CONSERVES ENERGY BECAUSE ONLY
NODES OF RANVIER GET DEPOLARISED.
Depending upon
DISTRIBUTION
they innervate smooth muscles , cardiac muscles and
AUTONOMIC NERVE FIBERS glands.
Their main work is to maintain homeostasis with the
help of autonomic nervous system.
they can lead to either excitation or inhibition of
effector organs.
PARASYMPATHETIC NERVE FIBERS PREGANGLIONIC POSTGANGLIONIC
Release acetylcholine in both. Release acetylcholine in case of
parasympathetic.
Release either acetylcholine or
norepinephrine in case of
sympathetic.
SYMPATHETIC AND
Myelinated B fibers. Unmyelinated C fibers are present in
the case of sympathetic .
Terminate on the postganglionic Terminate on visceral effector.
cyton
In case of sympathetic it is smaller In case of parasympathetic it is
than postganglionic nerve fiber and smaller than preganglionic nerve
vice versa for parasympathetic nerve fiber and vice versa for sympathetic
fiber. nerve fibre
ELECTROPHYSIOLOGY
Relationship of current and
capacitance for physiological system
CURRENT
♦ Electric current is define as the rate of flow
of charges passing through a point
or
Amount of charges (Q) passing per
unit time (t)
and is given as
Equation 1
CAPACITANC
• E of a capacitor to store charges
Is the ability
• A capacitor is made up of two conductive
plate that are separated by small distance or
a thin layer of dielectric (insulator) b/w two
conducting plates.
• The surface area of plates increases the
capacitance while the distance of dielectric
decreases the capacitance.
• When positive and negative ions are
separated by conducting substance a
potential difference generate across them
but when insulation is provided in between
them charges store there and do not flow.
Equation 2
RELATIONSHIP B/W CURRENT
AND CAPACITANCE
• Placing equation 2 (Q= CV)
in equation 1 (I= Q/t)
we get
I = CV/t
• We can conclude that current is directly
proportional to voltage and capacitance but
inversely proportional to time.
• Nerve Conduction Velocity (NCV) is
the speed of current passing through a
ELECTRICAL PROPERTIES
OF CELL
• CompareMEMBRANE
the plasma
membrane with a
capacitor , charges are
separated by lipid bilayer
through electrogenic
pump (Na+/K+ ATPase)
generating a voltage
across it
• The hydrophobic thin
layer of lipids act as an
insulator and membrane
become able to store
charges.
• Membrane of all cells in particular excitable
cells have many ionic gates which allow
flow of charges (current) through them after
receiving certain stimuli.
• Thus membrane is also a good conductor
of current.
• Depolarizing phase of Action potential is
similar to the flow of ions from a capacitor.
• While repolarizing phase is similar to the
restoring the charges for further impulses.
VARIOUS DIAGNOSTIC LAB TESTS
TORECORD ELECTRICAL ACTIVITY
OF DIFFERENT ORGANS
• EEG (Electroencephalogram of brain)
• EMG (Electromyography of muscles)
• ECG (Electrocardiogram of heart)
• ENoG (Electroneurograpghy of nerves)
• NCV (Nerve conduction velocity of
nerves)
NERVE CONDUCTION
VELOCITY
• Is the rate of propagation of electric signal
through a nerve.
• Or the distance covered by AP per unit
time.
• NCV = lambda /time
• From the equation we can see that NCV is
directly proportional to the Rm.
• While inversely proportional to the Cm.
• MYELINATION provide insulation and thus
decrease Capacitance although there is a
decrease in amplitude of current but
impulses are ensured to be very fast in ling
• nerves.
Nodes of Ranvier after few millimeter
provide conduction and propagation
of impulse in forward direction
• Invertebrates have unmyelinated short
neurons that is why AP are very rapid .
Commonly used method
for Animal Model
1. Dissect the frog Schiatic nerve.
2. Or the median and lateral giant axon of
earthworm.
3. Set-up the instrument (stimulator,
electrodes, wires and oscillator
and plates) and chemical (such as
Ringer buffer).
4. Place the nerve over electrodes.
5. Record the electrical activity.
6. Calculate NCV.
Procedure for Human
• NCVthe nerve to be studied.
Locate
• Small electrode will be taped to the skin over the
nerve after applying conducting gel.
• An stimulating electrode will be placed at a known
distance away from recording electrode.
• The nerve will be stimulated by a mild and brief
electrical shock.
• The patient may experience discomfort or pain due
to the shock.
• The stimulation of the nerve and the electrical
impulse and current will be displayed on an
oscilloscope (a monitor that display electrical
activity).
Observations
• Any decrease in the NCV will indicate:
1.Extent of demyelination of nerve
2. Any Conduction Block
3.Axonopathy (damage to the
long
portion of a nerve cell)
SIGNIFICANCE
•Diagnosis of various diseases
•Detection of source and location of conduction
Nerve impulse (resting state)
• The difference in the ion concentrations is all dependent on
the permeability of the axon membrane
• During the resting state the permeability of the membrane to K+
is high, due to the presence of the protein channels (gates)
• Due to there being no (gates) for the organic ions, they remain on
the inside of the membrane
• Due to the ions, this is the reason why there is a negative charge
on the inside of the axon membrane
• Very few K+ ions will diffuse out of the membrane, due to the fact that
there is an overall negative charge on the inside of the axon
membrane
• Cl- concentration gradient is towards the inside of the axon
membrane but due to overall negative charge, they are repelled back
out.
• Na+ would be expected to move into the axon membrane, due to the
overall negative charge. But there is a low permeability on the axon
membrane to sodium ions, so in turn they are moved inside slowly
and are captured by the ion pumps and expelled to the outside
Nerve impulse (generating)
• When a nerve impulse is generated the following occur
• Na+ permeability slightly increases, so more enter the axon
membrane than are being expelled
• Due to this movement the potential difference reaches a positive
value (action potential)
• So as the permeability to Na+ decrease in turn the permeability
to K+ increases due to more (K) channels being open.
• So as the K+ flow out, the potential difference inside the axon
decrease back to the negative resting value. There is slight
decrease in the membrane potential which is slightly lower than
resting potential, due to more K+ released than needed
• This effect is called the Hyperpolarisation. But this is temporarily
until the Na+ and K+ return to their resting concentrations
Action potential
Action potential
• A nerve impulse is the propagated (spread) action potential or a
wave of depolarisation which travels along the axon
membrane.
• The ion channels in the axon membrane are voltage
dependent, which only open when the membrane is
depolarised
• This sets up a current which spreads from the action
potential region of the membrane to the region ahead of it.
• This stimulates the Na+ channels to open. This occurs in a
small segment of the axon membrane
• Due to the propagated action potential, this moves at a constant
velocity along the axon membrane.
• Saltatory conduction is a type of conduction which only occurs
when the action potential jumps from one ‘node of ranvier’ to
another. This is because of the axon being myelinated. The
result is an increase in the conduction velocity
• During the passage of the nerve impulse the axon will gain
Na+
and lose K+, but these ions are re-exchanged by the Na+/
K+
SYNAPSE
Definition – Synapse
is the functional
communicating
junction between 2
nerve cells.
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TYPES
Anatomical types
Physiological types.
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ANATOMICAL TYPES
Axo-dendritic synapse
– between axon of one
to dendrite of other.
Axo-somatic – between
axon of one to
soma(body) of other.
Axo-axonic – between
two axons.
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PHYSIOLOGICAL TYPES.
Chemical – by
Neurotransmitter.(one
direction)
Electrical – transmission
through Gap junction.
(both direction)
Conjoint – Both chemical
& electrical transmission
co-exists.
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CHEMICAL SYNAPSE
Structure
Process
Inhibition
Properties
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STRUCTURE OF CHEMICAL
SYNAPSE
Synaptic knob or
button.
Pre synaptic
membrane.
Synaptic
cleft.
Post
synaptic
process.
Post synaptic
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membrane.
SYNAPTIC KNOB OR BUTTON.
Axon loses myelin sheath.
End into small swellings as
knobs
Contains Mitochondria &
Neurotransmitters in vesicles
Circular – excitatory
Flat – inhibitory.
Transport –by Microtubules.
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PRE SYNAPTIC MEMBRANE.
Inner side contains
zone of dense
cytoplasm.
This forms
Presynaptic vesicular
grid.
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SYNAPTIC CLEFT.
Gap between pre &
post.
20-40 nm wide.
Contains ECF with
Glycoproteins.
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POST SYNAPTIC PROCESS
POST SYNAPTIC MEMBRANE.
Region of receiving
neuron.
Also contains zone of
dense cytoplasm.
Contains no of receptor
proteins projecting
outwards in cleft.
Neurotransmitter attaches
to these receptors.
Thursday, February 1, 2018
RECEPTOR PROTEINS.
Two types.
Ion channel receptor
proteins (Na, K, Cl)-
activation causes
opening of these
channels.
Enzymatic types of
receptor proteins –
Activation of cellular gene
Activation of protein
kinase.
Thursday, February 1, 2018
PROCESS OF CHEMICAL
SYNAPTIC TRANSMISSION.
Release of
Neurotransmitters.
Development of
EPSP & IPSP.
Removal of
Neurotransmitter
from synaptic cleft.
Development of
Action potential.
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RELEASE OF
NEUROTRANSMITTERS.
Nerve impulse reaches
nerve terminal
Depolarization of pre
synaptic membrane
voltage gated Ca channels
open
Ca permeability
Ca enters.
Thursday, February 1, 2018
ACETYLCHOLINE
Principal NT released by cholinergic neurons.
At N-M junction.
Preganglionic & post-ganglionic Para-
sympathetic
Preganglionic Sympathetic.
Postganglionic sympathetic which innervates –
sweat glands & skeletal muscle blood vessels.
Ending of Amacrine cells of retina.
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ACETYLCHOLINE
Receptors – Nicotinic &
Muscarinic.
Synthesis & storage – in
Mitochandria by AchCoa
& stored in vesicles.
Actions – most places its
excitatory but few (vagus
supplying heart) –
inhibitory.
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MUSCARINIC VERSUS NICOTINIC
ACTIONS OF AcH.
FEATURES MUSCARINIC NICOTINIC
Site of action Post synaptic in Cardiac All Autonomic
muscle, Smooth muscle Ganglia
& Glandular cells. N-M junction in
skeletal muscles.
Characteristics of action Same as Mushroom Same as drug
poison – Muscarine. Nicotine.
Action – slow in onset. Action – Quick in
Duration - Prolonged. onset.
Duration – Brief.
Actions antagonised by Atropine Hexamethonium at
Autonomic Ganglia
Tubocurarine at
skeletal muscles.
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Phenylalanine
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DOPAMINE
Naturally acting Neurons – in Mid brain
precursors of NE. to
Striatum
Receptors
D1 – Activates adenyl cyclase Olfactory tubercle
via Gs protein Nucleus accumbens
D2 – Inhibit adenyl cyclase
via Gi protein. limbic system area.
D3 – Localised to Nucleus Highest conc present in
Accumbens.
Basal Ganglia, limbic
system & CTZ in medulla.
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FUNCTIONAL ROLES OF
DOPAMINE
Control of Movements
Induction of Vomiting.
Inhibition of Prolactin secretion & stimulation of
GnRH.
Retina – Inhibitory Neurons.
Schizophrenia type of Psychosis due to Increased
levels of D2 receptors.
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SEROTONIN.
Synthesis – from
Tryptophan.
Metabolism –
Inactivated by MAO to
5-hydroxy indole acetic
acid(5-HIAA)
Sites of secretion
In Brain
Non-neural cells.
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SEROTONIN.
Serotonin receptors –
7 group of receptors
(5HT1-5HT7) with further
groups A-F.
Functional role in CNS
Regulation of carbohydrate
intake & Hypothalamic
releasing hormones.
Pain inhibition.
Hallucination
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HISTAMINE
Sites of secretion
In Brain & Non-neural cells.
Histamine receptors
H1 – activates Phospholipase C
H2 – increases intracellular cAMP
H3 – inhibition of histamine via G protein.
Functional role
Excitatory
Arousal & sexual behaviour, Regulation of ant pituitary,
Drinking, Pain threshold & Itch sensation.
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SYNTHESIS & CATABOLISM OF
HISTAMINE.
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AMINO ACID
NEUROTRANSMITTERS
Excitatory
Glutamate – Brain &
dorsal sensory
nerve
Aspartate -
Cortical pyramidal
cells.
Inhibitory
GABA – whole CNS
Glycine. – Grey matter of
spinal cord & brain
stem.
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GLUTAMIC ACID
Synthesis – Mainly
from Glucose via Kreb
cycle or Glutamine,
synthesized by Glial
cells & taken by
neurons.
Receptors – High
conc in Hippocampus
& Cerebellum.
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GABA
Receptors – Formation of GABA.
A – Inhibition by
increasing Cl
conductance
B – By K
conductance
C – in Retina.
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NEUROPEPTIDE
TRANSMITTERS.
Mechanism of action –
Alter ion channel function, modify cell metabolism &
gene expression.
Types.
Neuroactive peptides – TRH, LH releasing hormone,
somatostatin.
Pituitary peptides – Vasopressin & Oxytocin.
Peptides acting on the Gut and Brain – Leucine,
Enkephalin, Methionine, Sub P, Cholecystokinin, VIP,
Neurotensin, Insulin, Glucose, Opioid polypeptides.
Thursday, February 1, 2018
INTRODUCTION
Neurotransmitters are chemical messengers that
transmit signals from a neuron to a target cell across
a synapse.
Target cell may be a neuron or some other kind of cell like
a muscle or gland cell.
Necessary for rapid communication in synapse.
Neurotransmitters are packaged into synaptic vesicles -
presynaptic side of a synapse.
Illustration of the major elements in chemical synaptic transmission.
A schematic representation of a chemical synapse
Axon
Pre synaptic Vesicles (containing
neurotransmitters)
knob Synaptic cleft
Receptors
Post synaptic
Receiving
knob neuron
PROPERTIES OF
NEUROTRANSMITTERS
1) Synthesized in the presynaptic neuron
2) Localized to vesicles in the presynaptic neuron
3) Released from the presynaptic neuron under
physiological condition
4) Rapidly removed from the synaptic cleft by uptake
or degradation
5) Presence of receptor on the post-synaptic neuron.
6) Binding to the receptor elicits a biological
response
TYPES OF NEUROTRANSMITTERS
EXCITATORY INHIBITORY BOTH
Glycine Acetylcholine
Glutamate
GABA Nor epinephrine
Aspartate
Serotonin
Nitric oxide
Dopamine
ACETYLCHOLINE (ACh)
Acetylcholine was the first neurotransmitter to be discovered.
Isolated in 1921 by a German biologist named Otto Loewi.
Uses choline as a precursor - cholinergic neurotransmitter.
Used by the Autonomic Nervous System, such as smooth muscles
of the heart, as an inhibitory neurotransmitter.
Responsible for stimulation of muscles, including the muscles of
the gastro-intestinal system.
Used everywhere in the brain.
Related to Alzheimer's Disease.
DOPAMINE
Is synthesized in three steps from the amino acid tyrosine.
Associated with reward mechanisms in brain.
Generally involved in regulatory motor activity, in mood,
motivation and attention.
Schizophrenics have too much dopamine.
Patients with Parkinson's Disease have too little
dopamine.
Dopamine
NOREPINEPHRINE (nor adrenaline)
Synthesized directly from dopamine.
Direct precursor to epinepherine.
It is synthesized in four steps from tyrosine.
Synthesized within vesicles.
Norepinephrine is strongly associated with bringing our
nervous systems into "high alert."
It increases our heart rate and our blood
pressure.
It is also important for forming memories.
Norepinephrine
GLUTAMATE
It is an amino acid
It the most commonly found
excitatory neurotransmitter in the brain.
It is involved in most aspects of normal brain
function including cognition, memory and learning.
Glutamate is formed from α –
ketoglutarate, an
intermediate of Kreb’s cycle.
γ-AMINO BUTYRIC ACID
(GABA)
Synthesized directly from glutamate.
GABA is the most important inhibitory neurotransmitter
Present in high concentrations in the CNS, preventing the
brain from becoming overexcited.
If GABA is lacking in certain parts of the brain, epilepsy
results.
GABA
SEROTONIN (5-HT)
Synthesized in two steps from the amino acid
tryptophan
Regulates attention and other complex cognitive
functions, such as sleep (dreaming), eating, mood,
pain regulation.
Too little serotonin has been shown to lead to
depression, anger control etc.
1.Neurotransmitters are
synthesized from precursors
under the influence of enzymes
2. Stored in vesicles
3.Neurotransmitter molecules
that leak from their vesicles are
destroyed by enzymes
4.Action potential cause vesicle
to fuse with synapse and release
neurotransmitters
5.Some of it binds with auto
receptor and inhibit subsequent
neurotransmitter release
6.Rest of it bind to post
synaptic receptors.
7.Released neurotransmitters
are deactivated either by re
uptake or enzyme degradation.
Steps in neurotransmitter processing are:
Synthesis: Neurotransmitters are synthesized by the
enzymatic transformation of precursors.
Storage: They are packaged inside synaptic vesicles.
Release: They are released from presynaptic terminal by
exocytosis when calcium enters axon terminal
during an action potential
Diffuse across the synaptic cleft to the
postsynaptic membrane.
Binding: They bind to receptor proteins.
Inactivation: The neurotransmitter is degraded either by
being broken down enzymatically, or reused by
active reuptake.
MODE OF ACTION OF ACETYLCHOLINE
• When nerve impulse reaches pre synaptic knob Ca
channels open.
• Increased Ca ions fusion of vesicle
Release
presynaptic
to membrane and release of ACh into cleft.
• ACh bind to receptors in post synaptic membrane.
• Ion channels open inflow of Na and K ions
• Depolarisation and formation of action potential.
Binding • Propogation of action potential & contraction of
fibres.
• ACh is hydrolysed by acetyl cholinesterase.
• Choline taken back to presynaptic domain for
Deactivation resynthesis of Ach.
ALCOHOL & NEUROTRANSMITTERS
It binds directly to receptors for ACh,
serotonin, GABA and glutamate.
It enhances the effects of the GABA,
which is an inhibitory
neurotransmitter.
◦ Enhancing an inhibitor make things
sluggish.
◦ The neuron activity is diminished-
sedative effects of alcohol.
Alcohol inhibits glutamate receptor
function.
◦ This causes discoordination, slurred speech, staggering,
memory disruption, and blackout.
NICOTINE &
NEUROTRANSMITTERS
Nicotine imitates the action of
ACh & binds to ACh receptor.
Like acetylcholine, nicotine leads to a burst of
receptor activity.
Nicotine activates cholinergic neurons in many
different regions throughout your brain
simultaneously.
This stimulation leads to:
◦ Increased release of glutamate.
◦ Stimulation of cholinergic neurons promotes the
release of dopamine. The production of dopamine
causes feelings of reward and pleasure.
DISEASES ASSOCIATED WITH
NEUROTRANSMITTERS
NEUROTRANSMITTER DISEASE
Acetylcholine Alzheimer’s
Dopamine Parkinson’s disease
Schizophrenia
GABA Epilepsy
Serotonin Migraines
ADD
Depression
Glutamate Migraine
stroke
MENINGES, VENTRICLES, CEREBROS
PINAL FLUID AND BOOLD SUPPLY
OF THE BRAIN
OBJECTIVES
• Illustrate and describe the Meninges’s three
membranes.
• Describe the structure of the meninges, its
blood supply and nerve supply.
• Illustrate and describe the venous blood
sinuses
The Meninges
• The Meninges are
the membrane
covering the brain and
spinal cord.
• The Meninges consist of
three membranes:
1. The dura mater,
2. The arachnoid mater,
3. The pia mater.
The Meninges
The Meninges
1. Dura mater - • 2. Arachnoid -
strong, "Tough mother" spidery, holds blood
a. Falx cerebri vessels
b. Falx cerebelli
c. Tentorium cerebelli • 3. Pia mater -
d. Diaphragma sella "delicate mother"
The Meninges
DURA MATER
Thick dense inelastic membrane
and the outermost layer of the
meninges
Bilaminar:
Endosteal layer (outer)
Meningeal layer (inner)
These are closely united except
along certain lines, where they
separate to form venous sinuses.
DURA MATER
Endosteal layer ;
o Periosteum - inner surface of the
skull bones
o Not continuous with
dura mater of spinal cord
Meningeal layer ;
o Dura mater proper
o Covering the brain
o Continuous with dura mater of
spinal cord
o Folded inwards as 4 septa
between part of the
brain
o The function of these septa is to
restrict the rotatory displacement
of the brain.
duramater
Superior
cerebral
veins
beneath
arachnoid
Superior sagittal sinus
Dura mater
(Dural venous sinus)
Endosteal layer
Meningeal layer
They are closely
united except along
certain lines; they
are separated to
form venous
sinuses
Subdural space
Coronal section of the upper part of the head
DURA MATER
Dura mater septa:
1. Falx cerebri
2. Falx cerebelli
3. Tentorium cerebelli
4. Diaphragma sella
Superior sagittal sinus Falx cerebri
Tentoriu
m
Frontal crest cerebelli
Crista galli
*
Inferior
sagittal sinus Straight
sinus
Arachnoid Mater
Delicate, impermeable &
avascular membrane covering the
brain
Lying between Pia mater
(internally) & dura
Mater(externally)
Separated from dura mater by a
potential space, the subdural
space (filled by a film of fluid)
Separated from pia mater by the
subarachnoid space (filled with
CSF)
The outer and inner surfaces
covered with flattened
mesothelial cells
Superior
cerebral
veins
beneath
arachnoid
Arachnoid mater
Arachnoid mater
Arachnoid projects into venous
sinuses
- sites for CSF diffuses into
bloodstream
Arachnoid
granulations
Arachnoid mater Arachnoid villi
Subarachnoid space Subdural space
SUBDURAL SPACE :
• Superior cerebral Superior cerebral veins
beneath arachnoid
veins, traverse the
subdural space to reach
the superior sagittal
sinus and its lacunae
*
Dura
Arachnoid
Subdural haematoma
Superior
cistern
Chiasmatic
cistern
Interpeduncular
cistern
Pontine Cerebellomedullary cistern
cistern
Median sagittal section to show the subarachnoid cisterns &
circulation of CSF
Pia mater
Arachnoid
Dura
Subarachnoid haemorrage
Pia Mater
It extends out over the cranial nerves & fuses
with their epineurium
The cerebral arteries entering the substance of
the brain, carry a sheath of pia mater with them
The pia mater forms the TELA CHOROIDAE .
The tela choroidae fuse with ependyma to form
the choroid plexus
Choroid plexus forms CSF
Choroid plexus of
lateral ventricle
Ependyma
Pia mater of
tela choroidae
Choroid plexus
of 3rd ventricle
Coronal section of the interventricular foramen showing the choroid
plexus of 3rd & lateral ventricles
VENTRICLES(Ventricular System)
• A ventricle is an internal
cavity of the brain. Within
the brain, which is filled
with cerebrospinal
fluid(CSF).
• The ventricular system is
composed of two lateral
ventricles and two midline
ventricles( third and fourth
ventricles).
VENTRICLES(Ventricular System)
• The chambers are
connected to allow the flow
of cerebrospinal fluid via
two interventricular
foramen (referred to as the
foramen of Monro) and the
cerebral aqueduct
(referred to as the
aqueduct of Sylvius).
Lateral ventricle
Interventricular
foramen (Monro)
Cerebral
aqueduct
Fourth ventricle
Third ventricle
Central canal of
medulla
oblongata &
spinal cord
Lateral view to show the ventricular system of the CNS
VENTRICLES(Ventricular System)
CONSISTS OF :
1) Lateral ventricle
2) Third ventricle
3) Fourth ventricle
4) Central canal of the
medulla oblongata
& spinal cord
42
CHOROID PLEXUS
• It is formed by invaginating
Lateral ventricle
of vascular pia mater into the
ventricular cavity
• It becomes highly convoluted
& produce a spongy-like
appearance
• It enters the 3rd and 4th
ventricles through their
roofs, and the lateral
ventricles through the
choroid fissure Third ventricle
• produces cerebrospinal fluid
Fourth
(CSF) ventricle