1. Neurotransmitters, reinforcement
Nisheeth
15th January 2019

2. Artificial neurons
Logical abstraction of natural neurons to perform these functions

3. Real neurons

4. 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

5. 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

6. 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

7. 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.

8. 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

10. 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

11. 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

12. 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

13. 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

15. Substance P
Neuropeptide Y

16. 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

17. 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

18. 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

19. 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