Dr.Kareem Darweesh Supervised by: Prof.

Mohammed Abd Elfattah

Basic Electrophysiology
In the resting state
Inside More negative than outside the cell The charges is mentained by the plzasma membrane: Ion channel(Na,K,Ca) Ion pump( Na-Ka adenosine triphosphatase pump)

Ion channels
Selective ,specific for ions
Two types: Ligand gated (open in response to ligand binding to receptor):

Excitatory neurotransmitters (EPSP): open cation channels (depolareize) (Glutamate receptor) Inhibitory neurotransmitters (IPSP): open Chloride channels (hyperpolerize) (GABA receptor)

Voltage gated

Action Potential
1.

Intracellular is negatively charged (-70-80)mV 2. Ligand Gated Ion channel open (Na Influx) 3. Less negativity inside 4. Till -55 mV (spike threshold) 5. Open the Voltage gated channels 6. Positively charged inside the neuron 7. Propagation along the axon

From Action Potential to neurotransmitters

At the terminus of the axon
Action potential trigger release of the

Neurotransmitter Action potential (all or none law)

Synapse
Pre synaptic membrane (the axonal terminal) Neuro transmitters synthesized Packaged Neurotransmitter receptors (regulatory) Voltage gated Ca channels Synaptic cleft (space btw the pre and post syn)
Post synaptic membrane Receptors

Receptors
Seven transmembrane domain receptor
Ligand Gated ion channel

Tyrosine kinase (family) : Changes in gene expression Bind to growth factors mediat the neurplasticity

Nerve growth factor Brain derived neurotropic factors

Seven transmembrane domain receptor

G-Protein Coupled receptors

Ligand Gated ion channel

Second messenger
Neurotransmitters are first messenger
The most common : cAMP cGMP Calcium ion inositol triphsphate IP3 Eicosanoid,NO,CO Activate protine kinase (one of the primary activities

of second messengers)

Neurotransmitters
Criteria of neurotransmitter Synthised in the neuron Released on depolarization from presynptic neuron Exogenous administration give the same effect Removed or deactivated by the neueron

Biogenic amines
The first to be discovered
The best understood Components: Synthesis Reuptake Degradation receptors

Dopamine
Ventral

tegmental area (mid brain) 4 pathways

Dopamine Pathways
Meso limbic system :to the Limbic system ,

amygdaloid Meso cortical : Frontal lobe Nigrostriatal tract : Substantia nigra Tubro infundibular : intermediat imnence and the posterior and intermediate lobe of pituitary

pathophisiology
in schizophrenia
depression reward system (cocaian)

Dopamine Synthesis

Dopamine removal
Reuptake mechanism
Degradation by COMT (cathecol-methyl transferase) MAO b

Dopamine Receptors

Serotonine
Median And

dorsal raphe nuclie (mid brain)

Serotonin synthesis

receptors
5-HT1A 5-HT1B Antidepressant action; partial agonist; anxiolytic Possible role in locomotor activity, aggression

5-HT1D
5-HT1E 5-HT1F 5-HT2A 5-HT2B 5-HT2C 5-HT3 5-HT4 5-HT5 5-HT5 5-HT6 5-HT7

Target of antimigraine drug sumatriptan

Unknown Target of antimigraine drug sumatriptan Target of hallucinogens, atypical antipsychotics Regulation of stomach contraction Regulation of appetite, anxiety, seizures; target of hallucinogens, antipsychotics Antagonists antiemetic, anxiolytic, cognitive enhancement Modulation of cognition, anxiety Unknown Unknown Target of hallucinogens, atypical antipsychotics Possible regulation of circadian rhythms

Serotonin removal
Reuptake mechanism
Degradation by COMT (cathecol-methyl transferase) MAO a (5-hydroxyindole acitic acid)

Norepinephriene
Noradrenergic pathways.
The locus ceruleus, which is located immediately underneath the floor of the fourth ventricle in the rostrolateral part of the pons, The projections reach many areas in the forebrain, the

cerebellum, and the spinal cord.

Norepinephriene receptors
Alpha (1a,b,c)(2a,b,c)
Beta (1,2,3)(cardiac,asthma,adipose tissue)

Alpha 2 (sedative anti hyper tensive) Alpha 2 a regulatory presynaptic (mirtazipin,

clonidine)

 Reuptake mechanism
Degradation by COMT (cathecol-methyl transferase) MAO a (5-hydroxyindole acitic acid)

Acetylcholine
nucleus basalis of Meynert projects to the cerebral

cortex and the limbic system Additional cholinergic neurons in the reticular system project to the cerebral cortex, the limbic system, the hypothalamus, and the thalamus Degeneration == alzheimer EPS

synthesis
acetylcoenzyme A | Choline acetyl transferase | acetylcholine

M1 M2 M3 M4 M5 NAChR

Regulation of cognition, seizures Regulation of cardiac function Regulation of smooth muscle contraction Target of antiparkinsonian anticholinergic drugs Unknown Regulation of tobacco use, seizures; possible cognitive enhancement

(GABA)
Highest concentrations are in the midbrain
synthesized from glutamate by the rate-limiting

enzyme glutamic acid decarboxylase requires pyridoxine (vitamin B6) Because GABA is thought to suppress seizure activity, anxiety, and mania, considerable effort has been devoted to synthesizing drugs that potentiate GABA activity

Glycine
Glycine is synthesized primarily from serine
double duty mandatory adjunctive neurotransmitter for glutamate activity independent inhibitory neurotransmitter at its own receptors hypothesis have shown a reduction in the negative

symptoms of schizophrenia by glycine.

Glutamate
synthesized from glucose and glutamine
primary neurotransmitter in cerebellar granule cells,

the striatum, the cells of the hippocampal molecular layer and entorhinal cortex, the pyramidal cells of the cortex Schizophrenia (Excitotoxic) Glutamate release is stimulated by nicotine play an essential role in learning and memory, NMDA receptor

Peptide Neuro transmitters

Peptide = Less than 100 amino acid
Systhized in the cell body by transcription and

translation of the DNA == RNA== mRNA== Peptides

Corticotropin-Releasing Factor (CRF)

two receptors, CRF1 and CRF2
modulating the organism's response to internal and

external stress depressed patients has elevated cortisol levels, sometimes evidenced by nonsuppression on a dexamethasone suppression test, CRF antagonist might be useful in the treatment of depression.

 Substance P afferent sensory neurons and in the striatonigral pathway, the perception of pain. Abnormalities affecting substance P ==Huntington's disease, dementia of the Alzheimer's type, and mood disorders. Neurotensin pathophysiology of schizophrenia, mostly because of its coexistence with dopamine in some axon terminals. Some preliminary reports suggest that neurotensin-related peptides or drugs have beneficial effects for some psychotic symptoms.

 Cholecystokinin schizophrenia. eating disorders and movement disorders. I t causes anxiety and triggers panic attacks in people with panic disorder. CCK antagonists are under study as possible anxiolytic agents. Somatostatin known as growth hormone-inhibiting factor. Has a role Huntington's disease and dementia of the Alzheimer's type.

 Vasopressin and Oxytocin two related peptides, have been postulated to be regulation of mood and most recently, social behavior. synthesized in the hypothalamus and are released in the posterior pituitary. Neuropeptide Y stimulate the appetite, and development of neuropeptide Y receptor antagonists is an active area of interest for obesity researchers.