Neurotransmitters, reinforcement Nisheeth 15th January 2019

Artificial neurons Logical abstraction of natural neurons to perform these functions

Real neurons

Two basic kinds of Neurotransmitters Excitatory: create Excitatory postsynaptic potentials: EPSP's stimulate or push neuron towards an action potential effect is merely to produce action potential- no behavioral effect as yet    Inhibitory: Create Inhibitory postsynaptic potentials: IPSP's Reduce probability that neuron will show an action potential Effect is merely to lessen likelihood of an action potential- again not   talking about behavioral effects just yet! Some neurotransmitters are both inhibitory and excitatory, depending upon  situation and location

Regulating Synaptic Activity Several ways to control synaptic activity Three kinds of synapses: Axodendritic: targets are dendrites Axosomatic: targets are soma Axoaxonic synapses Most common: Axoaxonic synapses: Releases NT onto terminals of presynaptic neuron Results in presynaptic excitation or presynaptic inhibition This increases or decreases presynaptic neuron’s release of the NT Does this by regulating amount of Ca+ entering terminal and thus increasing/decreasing NT release

Regulating Synaptic Activity Several ways to regulate how much neurotransmitter is released Autoreceptor activity: Autoreceptors regulate the amount of neurotransmitter released into the synapse Autoreceptors on presynaptic neuron detect amount of transmitter in cleft; regulate reuptake Like a thermostat If “temperature” is too low- release more NT If “temperature” is too high- release less NT

Glial cells also regulate NT function Glial cells surround and insulate neurons Prevent NT from spreading to other synapses Absorb some NT and recycle it for neuron’s reuse Can even release NT themselves: particularly glutamate This stimulates presynaptic terminal to increase or decrease NT release Contradicts Dale’s principle that neurons release one and only one transmitter at all of their synapses.

NT release modulation Alter rate of synthesis: more or less NT Alter storage rate: again, more or less NT Leaky vesicles Alter release: more or less release Alter reuptake: more or less SSRI’s Alter deactivation by enzymes: MAO inhibitors Block or mimic receptor site attachment Block and prevent attachment to receptors Mimic the NT at the receptor site

Why so many neurotransmitters? Not only different neurotransmitters, but different kinds of sub receptors for the same neurotransmitter Sub receptors are slightly different versions of the receptor site for the neurotransmitter Allows more specialization Allows more refinement of effects E.g. dopamine has at least 5 subtypes and short/long versions of at least one of those subtypes! Each has a different role in the processing dopamine Each serves a different function, and often a different behavioral function

Why so many neurotransmitters? Neurons can release more than one kind of neurotransmitter Dale’s principle was wrong! But, typically release one dominant kind of NT Most neurons release fast and slow acting NTs But: some release more than one fast Very, very complicated…..no where near understanding the actions completely

Why so many neurotransmitters? Release of Neurotransmitter = sending information signal Released in response to sensory information Produce reaction to the sensory information Thus: producing BEHAVIORAL changes Neurons tend to be grouped together by the type of neurotransmitter they release Not necessarily “areas”, but often highways E.g., a dopamine pathway is composed of mostly dopamine neurons which travel from one part of the brain to another Neurons travel in groups: In the CNS: these are called TRACTS In the PNS: these are called NERVES

Behavior vs. Neural Effects An “excitatory” neurotransmitter INCREASES the likelihood of an action potential An “inhibitory” neurotransmitter DECREASES the likelihood of an action potential This is different than the behavioral effect: An inhibitory neurotransmitter or drug may cause EXCITATION behaviorally! Alcohol: inhibits the inhibitory parts of the brain The part that says “don’t do that” The effect is EXCITATION of stupid behavior

Substance P Neuropeptide Y

Acetylcholine or ACh Two kinds of receptors Location Nicotinic: primarily in brain, spinal cord target organs of autonomic nervous  system Two kinds of receptors Nicotinic: nicotine stimulates Excitatory; found predominately on neuromuscular junctions Muscarinic Muscarine (mushroom derivative) stimulates Both excitatory AND Inhibitory; found predominately in brain Indicated effects: excitation or inhibition of target organs essential in movement of muscles important in learning and memory Too much: muscle contractions- e.g. atropine poisoning Too little: paralysis: curare and botulism toxin

Norepinephrine or NE At least two kinds: NE alpha and NE beta Called epinephrine in peripheral nervous system Also a hormone in peripheral system: adrenalin Chemically extremely similar to Dopamine, serotonin Located in brain, spinal cord certain target organs (heart, lungs) At least two kinds: NE alpha and NE beta Indicated effects: Primarily excitatory Fear/flight/fight system Too much: overarousal, mania, cardiac issues Too little: underarousal, depression, cardiac issues

Dopamine or DA At least 5 subtypes in two groupings: Location: primarily in brain frontal lobe, limbic system, substantia nigra At least 5 subtypes in two groupings: D1-like: D1 and D5 D2-like: D2, D3 and D4, with D2-short and D2-long Indicated effects: inhibitory: reduces chances of action potential involved in voluntary movement, emotional  arousal reward learning and motivation to get reward Critical for modulating movement and reward motivation Primary task is to inhibit unwanted movement Responsible for motivation to get reward: movement and initiative  Too little: Parkinson's disease: Treatment: INCREASE available DA via L-Dopa   Too much: schizophrenia Treatment: REDUCE available DA via antidopaminergics/antipsychotics  Amphetamines mimic this neurotransmitter

Serotonin or 5HT Located in brain and spinal cord Indicated effects 5-hydroxy-tryptomine Lots of 5HT receptors in the gut! Again at least three subtypes: 5-HT1A, 5-HT1C and 5-HT2 Indicated effects Both inhibition and excitation Important in depression, sleep, digestion and emotional arousal   chemically very similar to NE and DA Too little is linked to depression and sleep disorders Too much: Serotonin syndrome: confusion, twitching and trembling, dilated pupils, shivering, goosebumps, headache, sweating and diarrhea., irregular and fast heartbeat Many antidepressants are specific to this NT SSRI’s Block reuptake of 5HT in the synapse