Introduction to CNS

Montoya, Irene Jane M.

MS Pharmacy
CNS: brain spinal cord and the neuron

As the most complex system, the nervous system serves as the body
control center and communications network.
As a key homeostatic regulatory and coordinating system, it detects,
interprets, and responds to changes in internal and external conditions.
The brain
 The brain is composed of three
parts: the cerebrum (seat of
consciousness), the cerebellum,
and the medulla oblongata (these
latter two are "part of the
unconscious brain").

 The medulla oblongata is involved

with the regulation of heartbeat,
breathing, vasoconstriction (blood
pressure), and reflex centers

 The hypothalamus regulates

homeostasis.

 The cerebellum – muscle

coordination and maintains muscle
tone and posture
The Spinal Cord

White Matter vs. Gray Matter

Both the spinal cord and the brain consist of:
 white matter = bundles of axons each coated with a sheath of myelin
 gray matter = masses of the cell bodies and dendrites — each covered with
synapses.
 The CNS gives rise to PNS
 The ANS in under the control of
CNS and is also a part of the
PNS.
 The ANS is “automatic” and in
control of involuntary bodily
functions.
 ANS is divided into two parts:
 Sympathetic Nervous System
 Parasympathetic Nervous
System
 It regulates the function of
glands, the adrenal medulla,
smooth muscle tissue, organs
and the heart.
The neuron

 The neuron is the functional

unit of the nervous system.

 Humans have about 100 billion

neurons in their brain alone.

 While variable in size and

shape, all neurons have three
parts.
 Dendrites = into the cell
body
 The cell body
 The axon = away from the
cell body
 Neurons must be linked to each other in order to transmit
signals.

 The connection between two neurons is a synapse.

 When a nerve impulse (electrical signal) travels across a neuron

to the synapse, it causes the release of neurotransmitters.

 These chemicals carry the nerve signal across the synapse to

another neuron.
 Continuous conduction - nerve impulses are propagated
(transmitted) along the entire length of an axon.

 To transmit nerve impulses faster, some axons are partially coated

with myelin sheaths.

 These sheaths are composed of cell membranes from Schwann

cells.

 Nodes of Ranvier (short intervals of exposed axon) occur between

myelin sheaths.

 Saltatory conduction - Impulses moving along myelinated axons

jump from node to node.
The nerve message

 The plasma membrane of neurons has an unequal distribution of ions and

electrical charges between the two sides of the membrane.

 The outside of the membrane has a positive charge, inside has a

negative charge. This charge difference is a resting potential.

 Na + ions - outside the membrane

 K + ions - inside the membrane.

 This imbalance is maintained by the active transport of ions to reset the

membrane known as the sodium potassium pump.

 The sodium-potassium pump maintains this unequal concentration by

actively transporting ions against their concentration gradients.
The action potential

 Steps in an Action Potential

 At rest the outside of the membrane is more positive than the inside.
 Na moves inside the cell causing an action potential, w/c makes the inside
of the membrane more positive than the outside.
 K flow out of the cell, restoring the resting potential net charges.
 Na are pumped out of the cell and K are pumped into the cell, restoring the
original distribution of ions.

 The action potential begins at one spot on the membrane but

spreads to adjacent areas of the membrane.
 After passage of the action potential, there is a brief period, the
refractory period
 Passage of ions across the cell membrane passes the electrical charge
along the cell. The voltage potential is -65mV (millivolts) of a cell at rest
(resting potential).
 An action potential is a temporary reversal of the electrical potential
along the membrane for a few milliseconds.
Synapse and Synaptic Potential

A neurotransmitter is a chemical contained in a neuron which is

released by an action potential, crosses the synaptic cleft, and interacts
with a post-synaptic target to cause excitation or inhibition of that
target.
Ion Channels

 Cell pores or ion channels regulate

the electrical signaling that keeps the
cells of the brain and body functioning
and communicating with one another.
 They do this through a complex
process where a certain trigger opens
or closes the channels.
This change influences the flow of
electrically charged chemical
particles, known as ions, in and out of
the cells.
 Voltage-gated channel
 respond to changes in the
membrane potential of the cell
 are concentrated on the initial
segment of the axon and are
responsible for the fast action
potential.
 Voltage sensitive Ca and K
channels

 Ligand-gated channels (inotropic

receptors)
 opened by the binding of
neurotransmitters to the channel
 eg: nicotinic acetylcholine
receptor
 Metabotropic Receptors (G protein
coupled receptors)

 Modulate voltage-gated channels by:

 Membrane delimited pathway
 In this case, the G protein interacts
directly with the voltage –gated ion
channel (Ca and K channels)
 Ca channels = presynaptic inhibition
 K channels = slow postsynaptic
inhibition
 Generation of diffusable second
messengers
 eg. B adrenoreceptor generates
cAMP via activation of adenylyl
cyclase

 In contrast to the brief effect of

inotropic receptors, the effect of
metabotropic receptors can last
tens of seconds to minutes.
Central Neurotransmitters

 Amino Acids
 Neutral Amino Acids : Glycine and GABA
 Acidic Amino Acid : Glutamate

 These compounds are present in high concentrations in the CNS.

 And are extremely potent modifiers of neuronal excitability.

Neutral Amino Acids
 These are inhibitory and increase membrane permeability to
chloride ions, mimicking the IPSP.
 Glycine concentrations are particularly high in the gray matter of
the spinal cord.
 GABA receptors are divided into 2 types:
 GABA A – open chloride channels
 GABA B – coupled with G proteins that either inhibit Ca channels or activate K channels.
 In most regions of the brain, IPSPs have a fast and slow
component mediated by GABA A and GABA B receptors,
respectively.
Acidic Amino Acids
 Glutamate is present in very high concentrations in the CNS.
 almost all neurons that have been tested are strongly excited by
this amino acid.
 This excitation is caused by the activation of both inotropic and
metabotropic receptors.

 Inotropic receptors – 3 subtypes

 kainate (KA)
 a-amino-3-hydroxy-5-methylisoxazole-4-propionate (AMPA)
 N-methyl-D-aspartate (NMDA)
 Metabotropic receptors

 act indirectly on ion channels via G proteins

 selectively activated by ACPD (trans-1-amino-cyclopentyl-1,3-

dicarboxylate)

 Depending on the type of synapse, these receptors can initiate a

slow postsynaptic excitation or a presynaptic inhibition.

 Most excitatory synapses contain both NMDA and non-NMDA

receptors in the post-synaptic membrane.
 NMDA Receptors

 Has a critical role in synaptic plasticity, w/c is thought to

underlie certain forms of learning and memory.
 Selectively blocked by ketamine and phenylcyclidine
 These drugs enter and block the open channel.
Acetylcholine

 Most CNS responses to Ach are mediated by a large family of G

protein-coupled Mu receptors.

 At few sites, Ach causes slow inhibition of the neuron by activating

M2 subtype of receptor, w/c opens K channels.

 Usually causes slow excitation mediated by M1 receptors.

Monoamines

 cathecholamines ( dopamine and norepinephrine ) and 5-

hydroxytryptamine.

 Present in a very small amounts in the CNS

 Site of action of many drugs:

 CNS stimulants cocaine and amphetamine – cathecolamine synapses
 Cocaine blocks the reuptake of dopamine and norepinephrine
 Amphetamines cause presynaptic terminals to release these
transmitters
Dopamine
 Major pathway
 projection linking the substantia nigra to the neostriatum (levodopa)
 projection linking the ventral tegmental region to limbic structures
(antipsychotic drugs)

 2 categories:
 D1 – like
 D2 – like
 All dopamine receptors are metabotropic
 Dopamine generally exerts a slow inhibitory action on CNS neurons.
 D2 receptor activation opens K channels (dopamine-containing
substantia nigra neurons)
Norepinephrine
 Most regions of the CNS receive diffuse noradrenergic input.
 All noradrenergic receptor subtypes are metabotropic.
 When applied to neurons, norepinephrine can hyperpolarize them
by increasing K conductance.
 This effect is mediated by a2 receptors – on locus cereleus neurons
 In may regions of the CNS, NE enhances excitatory inputs by both
indirect and direct mechanisms.
 Indirect mechanism – involves disinhibition
 Direct mechanism – blockage of K conductances that slow neuronal
discharge
 This effect is mediated by either a1 or B receptors
5 – Hydroxytryptamine (Serotonin)
 5-HT is contained in unmyelinated fibers that diffusely innervate
most regions of the CNS. Has a strong inhibitory action.

 All are metabotropic except for 5-HT3.

 5-HT3 – inotropic receptor, exerts a rapid excitatory action

(limited sites only)

 5-HT1A – membrane hyperpolarization caused by an increase In K

conductance.

 Other regulatory functions of 5-HT-containing neurons include sleep,

temperature, appetite and neuroendocrine control.
Peptides

 Opiod peptides (enkephalins, endorphins, etc)

 Neurotensin
 Substance P -is the transmitter of primary afferents carrying pain.
 Enkephalins are the body's own morphine.
 Somatostatin
 Cholecytokinin
 Vasoactive intestinal polypeptide
 Neuropeptide Y
 Thyrothropin releasing hormone
Thank you!!!