1210 Week 18

1210 Week 18

1. Lecture 1

   • Neurotransmitters
     • major neurotransmitters
       • acetylcholine
       • amines
         • dopamine
         • noradrenaline
         • adrenaline
         • histamine
         • serotonin
       • amino acids
         • GABA
         • glutamate
         • glycine
       • peptides
         • dynorphin
         • enkephalins
         • neuropeptide gamma
         • somatostatin
         • substance P
         • thyrotropin - releasing hormone
         • vasoactive intestinal polypeptide
     • classifying neurotransmitters
       • must be synthesised in neurone
       • present in presynaptic terminal
       • released in sufficient amounts to exert its desired effect
       • when applied as a drug it mimics its endogenous form
       • there has to be a mechanism to remove it
     • end pate potentials are action potential dependent and MEPPS are miniature versions - they both are a result of the spontaneous release of a single vesicle, EPPs are multiples of MEPPs and are dependent on release of multiple vesicles
   • Neurotransmitter Release/Receptors
     • neurotransmitter synthesised - put in vesicles - secretion into cleft - binding to receptors - change in postsynaptic cell - neurotransmitter broken down - reabsorption of neurotransmitter
     • peptide neurotransmitters are sythesised in the soma
     • amine and amino acid neurotransmitters are synthesised in the synaptic terminal
     • stored in vesicles
     • small neurotransmitters are stored in clear-core vesicles (40-60nm) in the terminal
     • large neurotransmitters are stored in dense-core vesicles (90-250nm) in the soma/axon
     • a single neurone may release more than 1 neurotransmitter - co-existence/transmission
     • calcium triggers release and can also influence action potential shape
     • free vesicles are targeted to active zones on the membrane where they release after fusion
     • synatobrevin - bound to vesicle which binds to SNAP-25 on the membrane
     • synaptotagmin - calcium sensor, vesicle bound protein
     • metabotropic receptors - coupled to intracellular proteins and transduce the signal to the cell interior - slow responses
     • ionotropic receptors - form ion channels, depolarise/hyperpolarise the postsynaptic cell - fast responses
   • Transmission
     • electrical transmission - direct flow of ions from 1 neurone to another
     • gap junctions - made from 6 connexin subunits to form a connexon
     • gap junctions are modulated by pH, neurotransmitters, calcium concentration and may play a part in epileptiform activity
     • chemical transmission - neurotransmitter substance released from presynaptic neurone, diffuses across the cleft and produces an effect on the postsynaptic neurone

2. Lecture 2

   • Synapses/Neurotransmitters
     • electrical synapse - facilitate communication between neural cells - ions move directly between neurones - minority
     • chemical synapse - neurotransmitters diffuse across the synaptic cleft - majority
     • multiple synapses can contact 1 denrite
     • small neurotransmitters are syntheised by enzymes in the presynaptic neurone
     • large neurotransmitters are encoded for in the DNA
     • if stimulation is great enough there will be corelease of neurotransmitters
     • peptides start as prepropeptides and are cleaved to peptides removing the pre and pro
     • peptides are modulatory - substance P is a pain signal and opoids inhibit substance P release
     • opoids are a family of 20 peptides
     • termination of signal occurs in 3 ways
       • inactivation of the neurotransmitter e.g. acetylcholinesterase
       • reuptake of neurotransmitter - transporters on glia and neurones e.g. glutamate, GABA and serotonin
       • diffusion away from synapse - diffusion is slow so there is a long lasting action e.g. peptides
   • Examples
     • glutamate is released by over half of ball brain synapses and it generates excitatory responses
     • too much gluatmate is toxic and can cause ischemia, eplilepsy/seizures, hypoglycemia and trauma
     • GABA is released by a third of all brain synapses and generates an inhibitory response
     • GABA can reduce anxiety but is intoxicating
     • L-DOPA is used to treat Parkinsons - dopaminergic neurones in the substantia nigra degenerate in Parkinsons
     • benzodiazepines, barbiturates and alcohol can all cause the release of GABA
     • biogenic amines are amines produced by the bodies natural processes
     • dopamine and serotonin are involved in the reward system
       • antidepressants block serotonin reuptake
       • cocaine blocks dopamine reuptake
       • ecstacy increases the amount of dopamine and serotonin in vesicles for release
       • antipyschotics inhibit dopamine

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