Synaptic transmission and plasticity

Synaptic transmission and plasticity

1. Neurotransmitters

   • Glutamate, GABA, monoamines. Receptors- ionotropic, metabotropic, selective binding. ·       Neural integration: each presynaptic neuron may contact multiple post-synaptic neurons, each post-synaptic neuron may receive inputs from many different presynaptic neurons, integrate across many inputs, these inputs may combine to affect the probability of the postsynaptic neuron firing an action potential, basis of brains computing power ·       Postsynaptic receptors- released neurotransmitters bind to receptors. Ligand (chemical that binds with a receptor)- neurotransmitters are ligands and so are drugs. Binding site (place on a receptor where the ligand interacts) ·       Selectivity of binding- only specific ligands fit into a binding site due to the 3D shape of receptor, some drugs bind to more than one receptor ·       Affinity- how well a ligand binds to receptor, e.g. high affinity means that receptors are saturated (completely bound) by very dilute solutions of ligands ·       Ionotropic receptors- directly coupled to an ion channel, essentially is an ion channel, ligand binds -> ion channel opens ·       Metabotropic receptor- more complex, ligand binds to receptor, changes 3D shape of receptor, activates a G-protein connected to the receptor inside the neuron, activates an intracellular signalling cascade- can alter ionotropic receptors to make them more or less excitable or can alter protein synthesis ·       Receptors are not only found on postsynaptic neuron- negative feedback loop, retrograde signalling (signal from postsynaptic neuron to presynaptic neuron- may be important for synaptic plasticity) ·       Amino acid derivatives- glutamate- from glutamic acid, most abundant neurotransmitter, excitatory, binds to ~8 receptor types. GABA- made from glutamate, most abundant inhibitory neurotransmitter, binds to both ionotropic and metabotropic GABA receptors. Glycine- is an amino acid, binds to inhibitory receptors in spinal cord ·       Monoamines- mostly metabotropic, found in restricted groups of neurons, dopamine, serotonin, neuropeptides (opioids, heroin, morphine)

2. Synaptic Plasticity

   • A change in the input- output function.  The output is often consistent with the same input pattern (in normal cases/ not plasticity)

3. Long-term potentiation (LTP)

   • Bliss & Lomo- rabbit hippocampus, first demonstration of LTP, normal condition vs test condition, titanic stimulation (100 pulses of stimulation each second for a few seconds) What change might occur to alter post-synaptic response?- How many receptors there are, type and amount of neurotransmitter

4. Induction

   • NMDA receptors, magnesium block, depolarisation removes the block, calcium entry into post-synaptic neuron, blocking NMDA receptors impairs induction of LTP
   • Expression
     • More AMPA receptors, larger EPSP, more glutamate.

5. Associativity

   • Associating two active inputs
   • Cooperativity
     • Need multiple ligands/ inputs to be active simultaneously
     • Input specificity
       • LTP only occurs at the specifically stimulated synaptic sites, only those activated at the time

6. Long-term depression (LTD)

   • Increased responses are not the only long term effects of stimulation, low frequency stimulation results in a decreased response to test stimulation, most commonly observed in the cerebellum. May underlie motor learning. Co-exists with LTP and they can happen in the same time if in separate synapses. LTD can increase output.