NeuroPhysiology

Claire R. Berbano. MD

Human Central Nervous System

contains 100 billion neurons

Includes the neurons, the building blocks of the CNS

Main function of the neuron is to integrate and transmit nerve impulses

Glial Cells

comes from the Greek word glia for glue

2 major types:

Microglia – scavenger cells like macrophages that removes debris from

infection or injury

Macroglia – consists of oligodendrocytes, Schwann cells and astrocytes

Astrocytes

2 subtypes:

Fibrous astrocytes – intermediate filaments found primarily in white matter

Protoplasmic astrocytes – contains granular cytoplasm found in gray matter

Send processes to capillaries inducing them to form the blood-brain barrier

Axonal Transport

nerve cells have low threshold for excitation wherein the stimulus could
either be electrical, chemical or mechanical

Axosplasmic flow provides transport of proteins and polypeptides to axonal

ending

Orthograde transport = cell body to axon terminals (kinesin and dynein)

Retrograde transport = axon terminals to cell body

Wallerian Degeneration
Neurotropins

produced by astrocytes

transported to cell body via retrograde transport where they foster the
production of proteins necessary for neuronal growth, development and
survival

the first neurotropin to be recognized is the nerve growth factor (NGF)

others include brain-derived neurotropic factor (BDNF), neurotropin 3 or 4

NeuroPhysiology

Claire R. Berbano M.D.

Nervous System

senses and interprets the environment in an attempt to produce behavior

appropriate to that environment

Components

central nervous system (CNS) – brain and SC

peripheral nervous system (PNS)

a.) somatic NS

b.) autonomic NS

Nervous System

Brain is divided into 5 parts:

myelencephalon – medulla

metencephalon – pons/cerebellum

mesencephalon – midbrain

diencephalon – thalamus/hypothalamus

telencephalon – cerebrum

Cerebrospinal Fluid

supports the brain in the cranium

approximately 600-700 ml is formed each day

150ml are circulating in the subarachnoid space

not an ultrafiltrate of plasma

higher concentration of Na, Cl and Mg than plasma; while lower concentration

of K, glucose and Ca than plasma

production inhibited by diuretic and corticosteroid

Flow of Cerebrospinal Fluid

choroid plexus

foramina of Magendie/Luschka

3rd ventricle

cerebral aqueduct

4th ventricle

Medial and lateral aperture

subarachnoid space

arachnoid granulations/villi

Blood-Brain Barrier

composed of capillary endothelium and basement membrane of the

vasculature supplying the brain

brain capillaries have tight junctions, no gap junctions

lipid-soluble substances (carbon dioxide, oxygen) cross more easily

not present in pituitary gland, pineal gland, choroid plexus and some parts of
hypothalamus

Blood-Brain Barrier

Functions:

protects the brain from endogenous or exogenous toxins

prevents escape of neurotransmitter from their functional sites in the CNS

inflammation, irradiation and tumors may destroy the blood-brain barrier thus
permitting entry of noxious substances

Cerebral Blood Flow

about 80ml/100g/min (gray matter) and 20ml/100g/min (white matter)

is autoregulated (BP of 50 to 150 mmHg)

Chronic HPN (>150mm Hg) may disrup the BBB

regional metabolic activity helps determine regional CBF

If PCO2 increases, CBF also increases

If CBF decreases, EEG activity decreases

barbiturates constrict, volatile anesthetic dilates

Intracranial Pressure

contents of the cranium are noncompresible

an increase on one area can be compensated for by a decrease in another

if intracranial volume increases, ICP remains low until the compensatory

mechanisms are overcome, at which time ICP increases fairly rapidly

ICP acutely increase during coughing and Valsalva maneuver

Nerve Fiber Types

Sensory Receptors

Transducers that convert energy in the environment into action potentials in

neurons

Receptors respond by increasing permeability to Na and K producing a

receptor potential

Weber-Fechner law states that the magnitude of the sensation felt is

proprotional to the log of intensity of the stimulus

the generator or receptor potential is the nonpropagated depolarizing

potential in a sense organ after adequate stimulus.

Classification of Sensory Receptors

Sensory Transduction

Sensory Receptors

when a maintained stimulus of constant strength is applied, the frequency of

AP declines with time (adaptation or desenstitization)

Classification of receptors:
Mechanoceptors – touch and pressure

Nociceptors – pain, extreme heat or cold

Chemoreceptor – change in the chemical composition of the environment (eg.

taste buds, olfactory senses)

Photoreceptors – respond to light

a.) phasic receptors

- rapid and react strongly

- ex. Pacinian and Meissners corpuscles

b.) tonic receptors

- adapt slowly and incompletely

- ex. Ruffini’s, Merkel’s disks, muscle spindles and

nociceptors

Pacinian Corpuscle

unmyelinated tip of a sensory nerve surrounded by concentric lamellations

resembling an onion

detects deep pressure and fast vibration

Ruffini’s Corpuscle

deep skin receptors with a collagen filled capsule

detects sustained pressure

Meissner’s Corpuscle

dermal receptors and encode velocity of stimulus application (touch/flutter)

present in non-hairy skin

discriminatory touch and slow vibration

Merkel’s Disk

disk-like nerve endings that form synaptic connections with small receptive
fields

used for localizations of stimulus

Pain Receptors
nociceptors, free nerve endings (III,IV)

adapt extremely slowly

bradykinin and histamine released from damaged cells and activate

nociceptors

intensity of pain is related to the extent of tissue damage

report skin pain, visceral pain (poorly localized) and deep somatic pain (ex.
headache)

Pain Receptors

Fast pain

- acute, discretely localized pain (pinprick)

- small myelinated A-delta fibers (III)

- elicits the withdrawal reflex

Slow pain

- diffuse, chronic pain (burning)

- small unmyelinated C fibers

- sweating, nausea, changes in blood pressure and

muscle tone

Pain Receptors

pain impulses = lightly myelinated Aδ and unmyelinated C fibers

cold receptors = dendritic endings of Aδ and C fibers

heat receptors = C fibers

hyperalgesia = exagerrated response to a noxious stimuli

allodynia = sensation of pain in response to an innocous stimuli

Pain Sensations

substance P is the neurotransmitter at the synapses in the dorsal horn from

primary pain afferents

pain perception may be a function of subcortical centers but the cortex is

needed in interpreting the quality of pain
opiate receptors are seen in substantia gelatinosa and may inhibit substance
P

Pain Sensations

Stress-induced analgesia – pain disappears during a period of stress or

concentration on the matter at hand

Referred pain – pain referred from a viscus to a somatic structure that shares
the same embryologic dermatome

Projected pain – results from actual stimulation of a pain pathway anywhere

along the path causing it to manifest at the periphery of the pain pathway

NeuroPhysiology

Synaptic Transmission

Arrangements:

one to one synapses (NMJ)

- AP in presynaptic (motor nerve) produces an AP in postsynaptic (muscle)

many to one synapses (spinal motoneurons)

- many presynaptic to one postsynaptic cell to depolarize it to threshold.

Neuromuscular Junction

The synapse between axons of a motor neuron and a skeletal muscle fiber

Acetylcholine (Ach)

An acetyl ester of choline

Synthesized in the cytoplasm; catalyze by choline acetyltransferase

Taken up into synaptic vesicles by an active vesicular transport mechanism

Acetylcholinesterase, located in synaptic cleft and weakly associated with

postsynaptic membrane, terminates Ach via hydrolysis to acetate and choline

Choline undergoes active reuptake

Small amount of Ach that diffuses away is degraded by serum and

erythrocyte cholinesterases

Acetylcholine

used by all motor axons, autonomic preganglionic neurons, postganglionic

parasympathetic, and some cells of motor cortex and basal ganglia

major termination – enzymatic degradation

Adrenergic Transmission

similar with cholinergic transmission

the conversion of tyrosine to dopa via tyrosine hydroxylase is the rate-

limiting step and occurs in the cytoplasm

dopamine is converted into NE after vesicular uptake

reuptake is a major mechanism to terminate transmitter activity; second is

via diffusion

COMT is found in smooth muscle, liver and kidney tissues; not found in
adrenergic nerve endings

Formation of Norephineprine

Synapses Between Neurons

synapses are located on the cell body and dendrites

cell body/dendrites = ligand-gated (EPSP, IPSP)

axon/axon-hillock = voltage-gated (low threshold)

if the sum of all the inputs reaches threshold, AP will be generated

Excitatory Postsynaptic Potential (EPSP)

transient depolarization

moves membrane potential closer to threshold

increase conductance to Na and K

Na influx causes depolarization

similar to EPP in NMJ

excitatory neurotransmitters include ACH, NE, Epinephrine, Dopamine,

glutamate and serotonin

Inhibitory Postsynaptic Potential

(IPSP)

transient hyperpolarizations
moves membrane potential away from threshold

increase Cl conductance

Cl influx causes hyperpolarization

can also be produced by increased K conductance and K efflux

inhibitory neurotransmitters include GABA and glycine

Electrical Synapses

AP is transmitted from one cell to the other by the direct flow of current

can occur in both directions (bidirectional); faster than chemical synapses

(unidirectional)

joined together by gap junctions

Biogenic Amines

NE, epi, dopamine, serotonin and histamine

NE – primary NT for postganglionic sympathetic neurons

Epi – released by chromaffin cells in adrenal medulla

Serotonin – high amounts in brains stem

Histamine – hypothalamus

major termination - reuptake

Amino Acid

glycine, GABA, glutamate and aspartate

glycine – inhibitory transmitter in spinal interneurons and brainstem

GABA – inhibitory NT in CNS

GABA and glycine both generate IPSP via ligand gated Cl channels

Glutamate and aspartate generates EPSP

major termination - reuptake

Nitric Oxide

lipid-soluble; synthesized as needed

not packaged in vesicles nor released via exocytosis

readily diffuses across cell membranes

an inhibitory transmitter in CNS and ENS

also functions as a cellular signal transduction molecule in neural tissue and

vascular smooth muscle (endothelial-derived relaxing factor)

Agents Affecting Neuromuscular Transmission

Botulinum Toxin

– blocks release of Ach from presynaptic terminals

– causes total blockade

– Curare

– competes with Ach for receptors on motor end plate

– decreases EPP

– maximal dose can produce paralysis of respiratory muscles and death

Agents Affecting Neuromuscular Transmission

Neostigmine

– blocks anticholinesterase action

– prolongs and enhance action of Ach at muscle end plate

Hemicholinium

– blocks reuptake of choline into presynaptic terminals

– depletes Ach stores from presynaptic terminal