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Neurophysiology -Dr Sravanthi OBJECTIVES INTRODUCTION NEURON AND TYPES RESTING POTENTIAL ACTION POTENTIAL SYNAPSE AND TYPES REFLEX ARC NEUROTRANSMITTERS AND TYPES NERVOUS SYSTEM The Neuron The nervous system is made of nerve cells or neurons and glial cells. Glial cells are not excitable and provide metabolic and physical support for the neurons. 90% of the cells are glial cells. Neurons are excitable and control behavior STRUCTURE TYPES Ion channels Resting potential There is a potential difference between the inside and outside of as membrane. The inside is about -70 mv relative to the outside. Resting Potential The resting potential is caused by an uneven distribution of ions (electrically charged molecules) of potassium (K+) and sodium (Na+) and chloride (Cl-). This is caused by Na+/K+ ion pumps that move 3 Na+ ions out of the cell for every 2 K+ ions it moves in. Therefore there are more +ions outside the cell than inside and the inside is negatively charged with respect to the outside Ion pump Resting potential Forces maintaining the resting potential Diffusion pressure – molecules want to move from areas of high concentration to areas of low concentration. Electrostatic charge – ions with like charge are repelled and ions with a different charge are attracted. Operation of ion pumps and ion channels. Action potential Anything that alters the functioning of the ion channels can change the resting potential. If changes cause the resting potential to be reduced, this is called depolarization. If the change causes an increase in the resting potential, this is caused hyperpolarization. Action potential ACTION POTENTIAL 1.AP, activation of the voltage-dependent Na+ channels (soma, area of the initial segment) 2. ADP, after-depolarization, acctivation of a high threshold Ca2+ channels, localized in the dendrites 3.AHP, after-hyperpolarization, Ca2+ sensitive K+ channels 4.Rebound depolarization, low threshold Ca2+ channels, de-inactivated during the AHP, activated when the depolarization decreases (probably localized at the level of the soma Action potential Voltage gated ion channels open and let Na+ into the cell. They are driven into the cell because of diffusion gradient and electrostatic charge. This causes the resting potential to reverse, i.e., the inside the cell becomes positive. Now the Na+ ion channels close and the K+ channels open and the K+ ions are driven out of the cell because of their concentration gradient and electrostatic charge. Finally the K+ channels close and the ion pumps kick in and the resting potential returns to normal. All or None Law Action potentials when they occur are always the same. Once the process is initiated, it must run its course and nothing can stop it or change it Transmission of action potentials along a membrane When an action potential occurs at one place on the membrane of an axon, the surrounding membrane is depolarized past threshold causing an action potential. This depolarizes the neighboring membrane, etc. Action potentials sweep across a membrane as fast as 100m/sec Transmission of action potentials along a membrane SYNAPSE A junction that mediates information transfer from one neuron: To another neuron To an effector cell neuron – conducts impulses toward the synapse Postsynaptic neuron – transmits impulses away from the synapse Presynaptic Junction between two cells Site where action potentials in one cell cause action potentials in another cell Types of cells in synapse Presynaptic Postsynaptic TYPES a)axosomatic b)axodendritic c)axoaxonic TYPES: A)CHEMICAL SYNAPSE Components Presynaptic terminal Synaptic cleft Postsynaptic membrane When an action potential arrives at the terminal bouton, it causes Ca++ channels to open. This causes the vesicles to move to the membrane and release a chemical called a neurotransmitter to be released into the synaptic cleft. The neurotransmitter diffuses across the cleft and activates receptors on the postsynaptic membrane which cause changes on the resting potential by altering the functioning of ion channels. B)ELECTRICAL SYNAPSE Synapse Any neuron can have thousands of synapses on it Postsynaptic potentials The membranes of dendrites and cell bodies do not have action potentials. Instead, any depolarizing stimulus causes a post synaptic potential (PSP) which spreads out across the membrane. The depolarization is weaker the further it gets from the stimulus. When the stimulus is turned off, the PSP disappears. Postsynaptic potentials Postsynaptic potentials can either be excitatory (depolarization) or inhibitory. Excitatory and inhibitory potentials can summate both in time (temporal summation) and across the membrane (spatial summation) . The net effect of summation is reflected at the axon hillock where action potentials are generated. Post synaptic potential The change in the resting potential caused by the activation of a receptor site is called the post synaptic potential (PSP). IPSP – when the change causes hyperpolarization or makes the cell harder to fire, this is called an inhibitory post synaptic potential. EPSP – when the change causes depolarization, this is called an excitatory post synaptic potential. RESTING,EXCITED,INHIBITED NEURON Post synaptic potential The excitation and inhibition caused by all the active synapses on the dendrites and cell body are summed and the net effect is reflected in the rate at which the axon hillock generates action potentials Summation SUMMATION Dale’s Law A single neuron always produces the same transmitter at every one of its synapses. It is now known that the law is not always right. Terminating synaptic action Once the neurotransmitter is released into the cleft, there must be a means by which its activity is terminated. This can be accomplished two ways The neurotransmitter can be destroyed by an enzyme in the cleft The neurotransmitter can be reabsorbed back into the bouton (reuptake). NEUROTRANSMITTER REMOVAL Proteins Ion pumps, ion channels, etc., are large molecules of protein. Proteins are long strings of amino acids that can fold into many three dimensional shapes. The same protein can have different configurations, i.e., they can change shape. Receptors are protein molecules that change shape (are activated) by neurotransmitter molecules with a particular shape. Receptors Receptor sites can be part of an ion channel and when the receptor site is occupied by a neurotransmitter, the ion channel opens Reflex arc Knee-jerk reflex COMPONENTS Research on reflexes Ivan Petrovich Pavlov Russia nobelist 1904 Sir Charles Scott Sherrington Great Britain nobelist 1932 Behavior as a chain of reflexes? LOCUST Two pairs of wings Each pair beat in synchrony but the rear wings lead the front wings in the beat cycle by about 10% Proper delay between contractions of the front and rear wing muscles Second messenger cascade Second messenger molecules can activate a kinase which lasts for minutes and hours. Kinases can activate transcription factors (CREB and c-fos) which alter the expression of genes. Genes carry the codes for the creation of proteins including ion channels and receptor sites and this can cause permanent changes in synaptic function. autoreceptors The membrane of the presynaptic cell has many receptor sites which detect the neurotransmitter. This is a feedback system which regulated the amount of neurotransmitter released into the cleft Other signaling between neurons Neuromodulators are chemicals that can alter the effect of a neurotransmitter. Sometimes the postsynaptic membrane releases molecules that affect the presynaptic membrane. DSE- depolarization-induced suppression of excitation DSI – depolarization-induced suppression of inhibition. Axo-axonal synapses: axons may also have synapses NEUROTRANSMITTERS Chemicals used for neuronal communication with the body and the brain 50 different neurotransmitters have been identified Classified chemically and functionally Chemically: • ACh, Biogenic amines, Peptides Functionally: • Excitatory or inhibitory • Direct/Ionotropic (open ion channels) or Indirect/metabotropic (activate G-proteins) that create a metabolic change in cell types EXCITATORY Acetylcholine INHIBITORY Aspartate GABA Dopamine Glycine Histamine Norepinephrine Epinephrine Glutamate Serotonin CHEMICAL-NT’S Acetylcholine (ACh) Biogenic amines Amino acids Peptides Novel messengers: ATP and dissolved gases NO and CO BIOGENIC-NT’S Include: Catecholamines – dopamine, norepinephrine (NE), and epinephrine (EP) Indolamines – serotonin and histamine Broadly distributed in the brain Play roles in emotional behaviors and our biological clock AMINO ACID-NT’S Include: GABA – Gamma ()-aminobutyric acid Glycine Aspartate Glutamate Found only in the CNS PEPTIDES-NT’S Include: Act as natural opiates, reducing our perception of pain Substance P – mediator of pain signals Beta endorphin, dynorphin, and enkephalins Found in higher concentrations in marathoners and women who have just delivered Bind to the same receptors as opiates and morphine Neurohormones Substances that act at neuron receptor sites, but are not specific to an individual synapse. May be released far from the synapse. Act as a neuromodulator (modify the activity of a neurotransmitter) NOVEL MESSENGERS-NT’S Nitric oxide (NO) A short-lived toxic gas; diffuses through post-synaptic membrane to bind with intracellular receptor (guanynyl cyclase) Is involved in learning and memory Some types of male impotence treated by stimulating NO release (Viagra) • Viagra NO release cGMP smooth muscle relaxation increased blood flow erection • Can’t be taken when other pills to dilate coronary b.v. taken Carbon monoxide (CO) is a main regulator of cGMP in the brain Drugs mostly act on the nervous system by interacting with neurotransmission, They may: act on receptor sites and cause the same effect as a transmitter: agonism block a receptor site: antagonism decreasing activity of enzymes that destroy a transmitter block reuptake mechanisms blocking ion channels altering release of transmitter altering the action of neurohormones Synapses that use NE are nor adrenergic (remember, adrenaline is another word for epinephrine) DA are dopaminergic 5-HT are serotonergic ACh are cholinergic etc Acetylcholine: Broken down by AchE (acetylcholinesterase) Receptors: nicotinic and muscarinic nicotinic Stimulated Blocked Function nicotine Voluntary muscle control curare (neuromuscular junctions) muscarinic muscarine botox and nerve gasses atropine Involuntary muscle control Biogenic amines Serotonin, Dopamine Norepinephrine and Epinephrine Broken down by MAO and COMT Reabsorbed by transporter mechanisms Influenced by amphetamines and cocaine and SSRIs and SNRIs E and NE receptor sites alpha (α)and Beta (β) with subtypes 1 and 2 DA has 6 receptor subtypes D1 and D2....D6 with sub sub types a b c, etc Serotonin has 4 main receptor subtypes with sub sub types a b c etc. GABA Universally inhibitory transmitter Opens a Chloride ion channel which stabilizes the membrane and makes it harder to depolarize Drugs like benzodiazepines enhance the ability of GABA to open the ion channel. There are two types of GABA receptors; GABAA and GABAB. There are many different subtypes of GABAA receptors which control different functions. GABAB receptors are less common and use a second messenger GABA Glutamate excitatory transmitter NMDA receptor open ion channel and lets +ions into the cell the channels can be blocked by alcohol, solvents and some hallucinogens Peptides opioid type peptides enkephalins (5 amino acids) endorphines (16 to 30 amino acids) Receptor subtypes mu, kappa and delta THANK YOU