Intro to CNS

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Introduction to CNS

Montoya, Irene Jane M.

MS Pharmacy


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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.


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The brain is composed of threeparts: the cerebrum (seat ofconsciousness), the cerebellum,and the medulla oblongata (theselatter two are "part of theunconscious brain").

The medulla oblongata is involvedwith the regulation of heartbeat,breathing, vasoconstriction (bloodpressure), and reflex centers

The hypothalamus regulateshomeostasis.

The cerebellum musclecoordination and maintains muscletone and posture

The brain


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The Spinal Cord

White Matter vs. Gray MatterBoth 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 withsynapses.


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The CNS gives rise to PNS The ANS in under the control of

CNS and is also a part of thePNS.

The ANS is automatic and incontrol of involuntary bodily

functions.

ANS is divided into two parts:

Sympathetic Nervous System

Parasympathetic Nervous

System

It regulates the function ofglands, the adrenal medulla,smooth muscle tissue, organs

and the heart.


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The neuron is the functionalunit of the nervous system.

Humans have about 100 billionneurons in their brain alone.

While variable in size andshape, all neurons have threeparts.

Dendrites = into the cellbody

The cell body

The axon = away from thecell body

The neuron


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Neurons must be linked to each other in order to transmitsignals.

The connection between two neurons is a synapse.

When a nerve impulse (electrical signal) travels across a neuronto the synapse, it causes the release of neurotransmitters.

These chemicals carry the nerve signal across the synapse toanother neuron.


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

To transmit nerve impulses faster, some axons are partially coatedwith myelin sheaths.

These sheaths are composed of cell membranes from Schwanncells.

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

myelin sheaths.

Saltatory conduction - Impulses moving along myelinated axonsjump from node to node.


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The plasma membrane of neurons has an unequal distribution of ions andelectrical charges between the two sides of the membrane.

The outside of the membrane has a positive charge, inside has anegative 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 themembrane known as the sodium potassium pump.

The sodium-potassium pump maintains this unequal concentration byactively transporting ions against their concentration gradients.

The nerve message


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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 insideof 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 butspreads to adjacent areas of the membrane.

After passage of the action potential, there is a brief period, therefractory period

The action potential


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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.


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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.

Synapse and Synaptic Potential


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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 ofthe cells.

Ion Channels


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Voltage-gated channel respond to changes in the

membrane potential of the cell

are concentrated on the initialsegment of the axon and areresponsible for the fast actionpotential.

Voltage sensitive Ca and Kchannels

Ligand-gated channels (inotropicreceptors)

opened by the binding ofneurotransmitters to the channel

eg: nicotinic acetylcholinereceptor


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Metabotropic Receptors (G proteincoupled receptors)

Modulate voltage-gated channelsby: Membrane delimited pathway

In this case, the G protein interactsdirectly with the voltage gated ionchannel (Ca and K channels)

Ca channels = presynaptic inhibition

K channels = slow postsynapticinhibition

Generation of diffusable secondmessengers

eg. B adrenoreceptor generatescAMP via activation of adenylylcyclase

In contrast to the brief effect ofinotropic receptors, the effect ofmetabotropic receptors can lasttens of seconds to minutes.


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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.


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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.


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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 andmetabotropic receptors.

Inotropic receptors 3 subtypes

kainate (KA)

a-amino-3-hydroxy-5-methylisoxazole-4-propionate (AMPA)

N-methyl-D-aspartate (NMDA)


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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-NMDAreceptors in the post-synaptic membrane.


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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.


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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.


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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

Monoamines


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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)

Dopamine


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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 neuronaldischarge

This effect is mediated by either a1 or B receptors

Norepinephrine


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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 Kconductance.

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

temperature, appetite and neuroendocrine control.

5 Hydroxytryptamine (Serotonin)


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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

Peptides


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Thank you!!!

Intro to CNS

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