Neurophysiology PDF

Neurophysiology Dr. Adel Hussien Prof. of Medical Physiology Physiology dept.-Faculty of Medicine – Minia University  Introduction to physiology of CNS Learning objectives: By the end of this lecture student will be able to 1- Illustrate the functional classification of the nervous syst...

Neurophysiology Dr. Adel Hussien Prof. of Medical Physiology Physiology dept.-Faculty of Medicine – Minia University  Introduction to physiology of CNS Learning objectives: By the end of this lecture student will be able to 1- Illustrate the functional classification of the nervous system 2- Describe types of nerve fibers and properties of each one 3- Discuss what is synapse, its types, mechanism of synaptic transmission and synaptic potential 4- Discuss properties of synaptic transmission and factors affecting it 5- Know some examples for chemical transmitters at synapses  Introduction to physiology of CNS Nervous system controls all the activities of the body. It is quicker than other control system in the body, ( quicker than endocrine system). Nervous system is divided into two parts: 1. Central nervous system 2. Peripheral nervous system  1- CENTRAL NERVOUS SYSTEM Central nervous system (CNS) includes brain and spinal cord. It is formed by neurons and supporting cells called neuroglia Structures of brain and spinal cord are arranged into two layers, namely gray matter and white matter. Gray matter is formed by nerve cell bodies and the proximal parts of nerve fibers, arising from nerve cell body. White matter is formed by remaining parts of nerve fibers N.B. In brain, white matter is placed in the inner part and gray matter is placed in the outer part. In spinal cord, white matter is in the outer part and gray matter is in the inner part. Brain is situated in the skull. It is continued as spinal cord in the vertebral canal through the foramen magnum of the skull bone. Brain and spinal cord are surrounded by three layers of meninges called the 1- Outer dura mater, 2- Middle arachnoid mater and 3- Inner pia mater. The space between arachnoid mater and pia mater is known as subarachnoid space. This space is filled with a fluid called cerebrospinal fluid. Brain and spinal cord are actually suspended in the cerebrospinal fluid.  General structure of the CNS Brain includes: - Cerebrum - Cerebellum - Midbrain - Pons - Medulla oblongata Spinal Cord includes: - Cervical part - Thoracic part - lumbar part - Sacral part - Coccygeal part  2- PERIPHERAL NERVOUS SYSTEM Peripheral nervous system (PNS) is formed by neurons and their processes that arises from CNS and supplies all regions of the body. It consists of cranial nerves, arising from brain and spinal nerves, arising from the spinal cord. It is divided into two subdivisions: A. Somatic nervous system B. Autonomic nervous system A. Somatic Nervous System Somatic nervous system is concerned with somatic functions. It includes the nerves supplying the skeletal muscles. Somatic nervous system is responsible for muscular activities and movements of the body B. Autonomic Nervous System Autonomic nervous system is concerned with regulation of visceral functions. So, it is called involuntary nervous system. Autonomic nervous system consists of two divisions, sympathetic division and parasympathetic division. The unit of structure and function of the nervous system is the neuron Neuron is similar to any other cell in the body, having nucleus and all the organelles in cytoplasm. However, it is different from other cells by two ways: 1. Neuron has branches or processes called axon and dendrites 2. Neuron does not have centrosome. So, it cannot undergo division. N.B. Dendrite transmits impulses towards the nerve cell body. Usually, the dendrite is shorter than axon. Axon transmits impulses away from the nerve cell body. Dendrites and axons are usually called nerve fibers. On the basis of function, nerve cells are classified into two types: 1. Motor or efferent neurons neurons which carry the motor impulses from central nervous system to peripheral effector organs like muscles, glands, blood vessels, etc. Generally, each motor neuron has a long axon and short dendrites. 2. Sensory or afferent neurons. neurons which carry the sensory impulses from periphery to central nervous system. Generally, each sensory neuron has a short axon and long dendrites.  Classification of Nerve Fibers 1. DEPENDING UPON STRUCTURE Based on structure, nerve fibers are classified into two types: i. Myelinated Nerve Fibers Myelinated nerve fibers are the nerve fibers that are covered by myelin sheath. ii. Non-myelinated Nerve Fibers Nonmyelinated nerve fibers are the nerve fibers which are not covered by myelin sheath. 2. DEPENDING UPON DISTRIBUTION Nerve fibers are classified into two types, on the basis of distribution: i. Somatic Nerve Fibers Somatic nerve fibers supply the skeletal muscles of the body. ii. Visceral or Autonomic Nerve Fibers Autonomic nerve fibers supply the various internal organs of the body. 3. DEPENDING UPON ORIGIN On the basis of origin, nerve fibers are divided into two types: i. Cranial Nerve Fibers Nerve fibers arising from brain are called cranial nerve fibers. ii. Spinal Nerve Fibers Nerve fibers arising from spinal cord are called spinal nerve fibers. 4. DEPENDING UPON FUNCTION Functionally, nerve fibers are classified into two types: i. Sensory Nerve Fibers Sensory nerve fibers carry sensory impulses from different parts of the body to the central nervous system. These nerve fibers are also known as afferent nerve fibers. ii. Motor Nerve Fibers Motor nerve fibers carry motor impulses from central nervous system to different parts of the body. These nerve fibers are also called efferent nerve fibers. 5. DEPENDING UPON SECRETION OF NEUROTRANSMITTER Depending upon the neurotransmitter substance secreted, nerve fibers are divided into different types: i. Adrenergic Nerve Fibers Adrenergic nerve fibers secrete noradrenaline. ii. Cholinergic Nerve Fibers Cholinergic nerve fibers secrete acetylcholine. 6. DEPENDING UPON DIAMETER AND CONDUCTION OF IMPULSE On the basis of diameter (thickness) of the fibers and velocity of conduction of impulses: i. Type A nerve fibers ii. Type B nerve fibers iii. Type C nerve fibers. Velocity of impulse through a nerve fiber is directly proportional to the thickness of the fiber. Type A nerve fibers are the thickest fibers and type C nerve fibers are the thinnest fibers. Except type C fibers, all the nerve fibers are myelinated. Type A nerve fibers are divided into four types: alpha, beta, gamma, and delta Type Diameter (μ) Velocity of conduction (meter/second) Aα alpha 12 to 24 70 to 120 Aᵦ beta 6 to 12 30 to 70 Aγ gamma 5 to 6 15 to 30 Aδ delta 2 to 5 12 to 15 B 1 to 2 3 to 10 C < 1.5 0.5 to 2  Synapse Site where axon of one neuron terminates on dendrites, soma (cell body) or axon of another neuron. Notice that: - Synapse is a place of contact (no continuity) between presynaptic and postsynaptic neurons - A small space separate the pre and postsynaptic neurons called the synaptic cleft in which a chemical transmitter is released Functional anatomy (structure) of synapse: 1- Terminal knobs - Mitochondria - Vesicles - Attachment proteins (V SNARE - T SNARE) 2- Synaptic cleft: 30-50nm ECF: rich Na-Cl-Ca poor K 3- Postsynaptic membrane Receptors - Ionotropic: ligand gated channels - Metabotropic: G protein coupled Receptors  Types of synapses According to site of contact: 1- Axo-dendritic 2- Axo-somatic 3- Axo-axonic According to mode of transmission: 1- Electrical synapse: rare contain gap junctions 2- Chemical synapse: common use chemical transmitter  Mechanism of synaptic transmission 1- Arrival of nerve impulse 2- Opening of Ca2+ channels 3- Release of chemical transmitter 4- Crossing synaptic cleft 5- Binding to receptor 6- Change postsynaptic Membrane permeability 7- Development of post-synaptic potential 8- Removal of the transmitter  Postsynaptic potentials (PSP) Definition: Local state of change in the postsynaptic membrane potential Types of postsynaptic potentials: 1- Excitatory postsynaptic potential (EPSP) 2- Inhibitory postsynaptic potential (IPSP) 3- Grand postsynaptic potential 1- Excitatory postsynaptic potential (EPSP) Local state of partial depolarization at the postsynaptic membrane Cause: binding of excitatory transmitter with its receptor….opening of Na+ channels…..Na+ influx….partial depolarization EPSPs can be summated* and reach threshold value and produce propagated action potential *types of summation a. Spatial summation Simultaneous stimulation of several Presynaptic neurons on postsynaptic membrane b. Temporal summation Multiple stimulations by one Presynaptic neuron on postsynaptic membrane 2- Inhibitory postsynaptic potential (IPSP) Local state of partial hyperpolarization at the postsynaptic membrane Cause: binding of inhibitory transmitter with its receptor….opening of Cl &K channels or closure of Na+ and Ca2+ channels….partial hyperepolarization IPSPs can be summated by both types of summation - Spatial summation - Temporal summation  Modulation of presynaptic potential Occurs by a 3rd neuron terminates on the presynaptic neuron and may lead to 1- Presynaptic inhibition rd 3rd neuron Presynaptic neuron If the 3 neuron is inhibitory..inhibitory transmitter Close Ca or Na channels or open K channels.. Decrease Ca entery..inhibition of release of the chemical transmitter 2- Presynaptic facilitation If the 3rd neuron is excitatory..excitatory transmitter Increase cAMP…phosphorylate K channels.. Postsynaptic neuron Close K channels…prolong depolarization..prolong opening of Ca channels…Increase release of the chemical transmitter  Mechanisms of synaptic inhibition A- Direct postsynaptic inhibition Inhibitory presynaptic neuron When inhibitory presynaptic neuron relies directly on postsynaptic membranes Postsynaptic neuron inhibited B- Indirect presynaptic inhibition excitatory presynaptic neuron 3rd inhibitory neuron When inhibitory third neuron rely on excitatory presynaptic nreuron Postsynaptic neuron inhibited  Properties (characters) of synaptic transmission 1- Forward direction (one way conduction): only from presynaptic neuron to postsynaptic neuron not the reverse 2- synaptic delay: 0.5 msec delay representing the time needed for synaptic transmission Number of synapses in reflex pathway = time of central delay / 0.5 3- Synaptic fatigue: decrease rate of discharge at the postsynaptic neuron due to rapid repetitive stimulation of the presynaptic neuron (decrease or block of impulse transmission at the synapses) Cause: a- exhaustion of synaptic vesicles b- inactivation of postsynaptic receptors Clinical value: prevent overexcitation in the CNS (in epileptic fits) 4- Synaptic plasticity: Ability to change the function of synapse according to the demand Synaptic transmission can be increased or decreased for short or long duration (1) Short term plasticity a) Short term inhibition (habituation): Gradual loss of response to a benign (habituated) stimulus when it is repeated for several times at intervals Cause: gradual inactivation of Ca channels…decrease intracellular Ca….decrease release of the chemical transmitter from the presynaptic neuron b) Short term facilitation - Post tetanic potentiation: brief rapid tetanizing stimuli…potsynaptic discharge for few seconds to mins after stoppage of stimulation Cause: repeated stimuli..increase intracelluar Ca…continuous releae of the chemical transmitter (immediate memory) - Sensitization: augmented response in the post synaptic neuron due to application of a noxious stimulus with a benign stimulus to the presynaptic neuron (short term memory) - Cause : presynaptic facilitation (2) Long term plasticity (a) Long term potentiation: prolonged stimulation of postsynaptic neuron due to repeated presynaptic stimulation, lasts for days or weeks Mechanism: occurs specifically in the hippocampus and responsible for long term memory Presynaptic stimulation…glutamalte…AMPA-NMDA receptors….increase Na influx…..depolarization of postsynaptic neuron (more than 20mV)….activation of NMDA receptors…increase Ca entry…Ca-calmodulin complex….activate kinase enzymes…. - Activation of AMPA receptors…more Na influx - Recruitment of more AMPA receptors into the postsynaptic membrane - Release of certain chemical signals (arachidonic acid and NO gas) from the postsynaptic neuron to act on the presynaptic neuron ….more increase of glutamate N.B. α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) and N-methyl-D-aspartate (NMDA), respectively. (b) Long term depression: prolonged depression of postsynaptic neuron due to repeated presynaptic stimulation - The postsynaptic membrane is depolarized to less than 20 mV so NMDA receptors continuously closed and Ca influx does not occur - Important for coordination (cerebellum)  Factors affecting synaptic transmission (A)Internal environmental changes 1- H+ ion concentration( pH of blood): synaptic transmission is very sensitive to pH changes Alkalosis: increase synaptic transmission Cause: hyperventilation…may lead to convulsions Acidosis: decrease synaptic transmission Cause: diabetes mellitus….increase ketone bodies may lead to coma 2- Hypoxia: decrease synaptic transmission Hypoxia for 3-5 sec….coma Prolonged hypoxia…..brain damage 3- Hypoglycaemia: decrease synaptic transmission (glucose is the main fuel for the nervous system) 4- Hormones: may facilitate or inhibit synaptic transmission 5- Electrolytes: decrease extracellular Ca2+ concentration…increase excitability of post synaptic neuron and synaptic transmission…tetany (B) Drugs 1- Drugs increase synaptic transmission - Theophilline, theobromine, caffeine act by increasing depolarization of postsynaptic membrane - Strychnine inhibit the effect of GABA (inhibitory transmitter)….more excitatory pathways…increase synaptic transmission….may lead to convulsions, muscle spam and death 2- Drugs decrease synaptic transmission Analgesics, anesthetics and hypnotics…due to hyperpolarization and decrease synthesis and release of the transmitter (C) Diseases Tetanus: neurotoxin prevent release of GABA…severe muscle Spasm (spastic paralysis) start in jaw muscles then respiratory muscles..death Botulism: botulinium toxin may present in canned food...blocks the release of Ach….flaccid paralysis  Chemical transmitters (1) Small molecules (rapidly acting transmitters) - Responsible for acute rapid responses of the nervous system - Examples include Acetylecholine Amines like norepinephrine , dopamine, serotonin, histamine Amino acids, excitatory as glutamate and aspartate and inhibitory as GABA and glycine (2) Large molecules (slowly acting neuropeptides) - Highly potent and more prolonged action than small molecules transmitters Types: - Hypothalamic: releasing peptides TRH CRH - Pituitary: GH, TSH, ADH - Opioid peptides: endorphins. Enkephalins - GIT peptides: gastrin, CCK, secretin - Others: substance p, neuropeptide Y, angiotensinII , ANP Which of the following is difference between IPSP and EPSP? a. Being of shorter duration b. Being unable to summate spatially c. Moving the membrane potential away from threshold d. Depending upon opening of voltage K + channels Which of the following is not inhibitory for synaptic transmission? a. Oxygen lack b. Alkalosis c. Acidosis d. Prolonged activity of synapse Enumerate 3 properties (characters) for synaptic transmission: 1-……………………………………………………… 2-………………………………………………………. 3-……………………………………………………….