Neurotransmitters Chemical communicators

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 – Axosmatic: targets are soma – Axoaxonic synapses 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 Also autoreceptor activity: 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 regulate NT function Remember: 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!

Many different ways of manipulating neurotransmitters 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

Neurotransmitters Specific Neurotransmitters have specific effects

Why so many neurotransmitters? Not only different neurotransmitters, but different kinds of sub receptors for the same neurotransmitter – 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 processing dopamine 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 – Neurons travel in groups: – In the CNS: these are called TRACTS – In the PNS: these are called NERVES

Acetylcholine or ACh Location – 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: curarae and botulism toxin

Norepinephrine or NE 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 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 Drugs such as sudafed may affect NE

Dopamine or DA Location: – primarily in brain – frontal lobe, limbic system, substania nigra At least 5 subtypes in two groupings: – D1-like: D1 and D5 – D2-like: D2, D3 and D4, with D2short and D2long 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 Too much: schizophrenia Amphetamines mimic this neurotransmitter

Serotonin or 5HT Located in brain and spinal cord Again at least three subtypes: – 5-HT1A, 5-HT1C and 5-HT2 Indicated effects – Both inhibition and excitation – important in depression, sleep and emotional arousal – 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

Amino Acids Gamma-aminobutryic Acid or GABA – Predominant inhibitory NT – GABA deficiency related to epilepsy, seizure disorders – Receptors respond to alcohol – Benzodiazepines mimic or act like GABA – Too much: oversedation, overrelaxing of muscles (including heart, respiration) – Too little: anxiety!

Amino Acids Glutamate: – Principal excitatory NT in central nervous system – Critical for learning – May play significant role in schizophrenia: disrupts regulation of DA Glycine: – Inhibitory NT in spinal cord and lower brain (brain stem) – Regulates motor activity by inhibiting unwanted movement – Strychnine poisoning: alters glycine activity and results in death

Neuromodulators: Neuropeptides and Gases Neuromodulators: do not directly excite or inhibit postsynaptic neuron increase or decrease release of NT by altering response of postsynaptic cells to various inputs In a way, are helpers to neurotransmitters Peptides = chains of amino acids – Endorphins: related to regulation of pain and feeling of reinforcement – Substance P: transmitter involved in sensitivity to pain; may also be important in schizophrenia – Neuropeptide Y: critical for metabolic functions, especially eating Gases such as Nitric Oxide: – serves as retrograde NT (that is, a backwards NT) – influences presysnaptic membrane’s release of NT – Viagra: increases nitric oxide’s ability to relax blood vessels – produce penile engorgement – But, moves blood from head, chest to penis – Related to eye problems and can cause heart arrhythmias