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– Axosomatic: targets are soma– Axoaxonic synapses

• Axoaxonic synapses:– Releases NT onto terminals of presynaptic neuron– Results in presynaptic excitation or presynaptic inhibition– This increaseses 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

Many different ways of manipulating neurotransmitters

• Alter rate of synthesis: more or less NT• Alter storage rate: again, more or less NT– Alter vessicles themselves: 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

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 of NE receptors: NE alpha and NE beta

• Indicated effects: – primarily excitatory– appears to modulate Fear/flight/fight system

• Too much: overarousal, mania• Too little: underarousal, depression

• Drugs such as sudafed, asthma medications, heart medications 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• Many antidepressants are specific to this NT– SSRI’s– Block reuptake of 5HT in the synapse

Amino Acids• Glutamate:

– Principal excitatory NT in central nervous system– Critical for learning– May play significant role in schizophrenia: disrupts regulation of DA

• 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

• 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 • but increase or decrease release of NT by altering response of

postsynaptic cells to various inputs

• Peptides = chains of amino acids– Endorphins: related to regulation of pain and feeling of reinforcement– Substance P: transmitter involved in sensitivity to pain– Neuropeptide Y: critical for metabolic functions, especially eating

• Gases such as Nitric Oxide: – serves as retrograde NT; – influences presysnaptic membrane’s release of NT– Viagra: increases nitric oxide’s ability to relax blood vessels and

produce penile engorgement