1. Glial cells and moving across the synapse
Neural Transmission
Glial cells and
moving across the synapse

2. Again: Three Stages of Potential
Resting potential:
Voltage is about -70mV
Dendrites receive incoming signals
If sufficient, cell goes into firing mode
Action potential
Voltage changes from -70mV to +40mV
Ions exchange places
Repeats itself rapidly down axon
Only in places where myelin sheath doesn’t cover: Nodes of Ranvier
Refractory Period:
below resting or lower than -70mV
Cell recovers from firing
Absolute refractor period: Brief time period when cannot fire again
Relative refractory period: Brief time period when difficult for it to fire again.

3. Now: Why an action potential?
Allows release of neurotransmitter
Neurotransmitter is chemical
Several specific kinds- each act on certain neurons
Most neurons respond to and release one kind of neurotransmitter
Neurotransmitter stored in synaptic vesicles
Action potential opens channels that allow Ca+ ions to enter terminals from extracellular fluid
Ca+ ions cause vesicles nearest the membrane to fuse with membrane
Membrane then opens and transmitter is dumped into synapse
Diffuses across synapse to postsynaptic neuron and attaches to chemical receptor

6. Action in the Synapse Neurotransmitter is released into the synapse
diffuses across synapse to next neuron’s dendrite
This “next dendrite” is post-synaptic  
Neurotransmitter is attracted to the POST-synaptic side:
  receptor sites on the next neurons dendrites
  attach if can find right spot: neurotransmitter must match molecular shape of receptor site

7. Action in the Synapse
Activation of receptor causes ion channels in membrane to open
Ionotropic receptors open channels directly to produce immediate reactions required for motor and sensory processing
Metabotropic receptors open channels indirectly and more slowly to produce longer-lasting effects
Sets off graded potentials for next action potential
Movement across the synapse is relatively slow: several milliseconds

9. Excitation and Inhibition
The NT opens ion channels on dendrites and soma
Two effects on local membrane potential:
shifts in positive direction (towards 0), partially depolarizing
Shifts in negative direction (away from 0): hyperpolarization
Thus two effects:
Excitatory: depolarization
Inhibitory: hyperpolarization

10. Two kinds of postsynaptic potentials:
EPSPs: excitatory postsynaptic potentials
Excitatory effect: increases likelihood of action potential
Opens Na+ channels
IPSPs: inhibitory postsynaptic potentials
Inhibitory effect: decreases likelihood of action potential
Opens K+ channels
Thus: bidirectional effects
Summative effects
Overall change must be sufficient to produce action potential

11. Postsynaptic integration
Summation across all the IPSPs and EPSPs
Summates algebraically
Adds both positive and negatives together
Two kinds:
Spatial summation:
Sum of all IPSPs and EPSPs occurring simultaneously at different locations along dendrites and cell body
Must be sufficient number of “hits”
Temporal summation
Sum of all IPSPs and EPSPs occurring within a short time
Must occur within a few milliseconds
Must get sufficient number of “hits” within certain time
Neuron is an information integrator!
A decision maker
Small microprocessor

12. Terminating synaptic activity
Neurons are efficient
Not all neurotransmitter is attached to post-synaptic receptor sites
Extra must be destroyed or repackaged
Enzymes in synapse attack and destroy extra NT
e.g., Monoamine oxidase or MAO, acetylcholinesterase
Attach and degradate neurotransmitter
MAO inhibitors stop this process and prolong action of dopamine, norepinephrine and serotonin in synapse:
e.g., Elavil
Reuptake
Neuron takes NT back up and recycles it for later use
There is a specialized autoreceptor that detects how much extra
Specialized transporter attaches to NT and brings it back into cell
SSRI, NSRI and SNSRI drugs do this block this action
E.g., prozac, lexapro, wellbutrin, etc.

14. So: Put it all together
Neuron receives incoming NT which attaches to receptor sites on dendrites
Results in local potentials: excitatory or inhibitory
If sufficient, produce an action potential
The action potential involves exchange of ions and opening of cell wall along axon hillock and nodes of Ranvier
The action potential is nondecremental or saltatory conduction
Results in moving down of synaptic vessicles and fusing of synaptic vessicles to terminal button wall
Neurotransmitter is released in synapse
Most makes it to the next neuron (dendrites)
Some may be degraded by enzymes
Some may be reuptaken
Some may float away
And so it all begins again, billions of times per minutes.

15. Chemical communicators
Neurotransmitters
Chemical communicators

16. 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

17. 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 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

18. 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

19. 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

22. 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

24. 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: curarae and botulism toxin

25. 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
Is a MONOAMINE
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

26. Dopamine or DA At least 5 subtypes in two groupings: Location:
Primarily in brain
Frontal lobe, limbic system, substania nigra
Is a MONOAMINE
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
iIvolved 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 symptoms
 Too much: schizophrenia-like symptoms
 Amphetamines mimic this neurotransmitter

27. Serotonin or 5HT
Located in brain and spinal cord
Again at least three subtypes:
5-HT1A, 5-HT1C and 5-HT2
Is a MONOAMINE
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: Serotonin Selecltive Reuptake Inhibitors
Block reuptake of 5HT in the synapse

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

29. Amino Acids Glutamate: Glycine:
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

30. 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