CNS, Neurotransmission

Question 1

How do Neurons Differ from Other Cells?

Answer 1

Neurons do not reproduce or replace themselves to the same degree as other cells

Neuroplasticity: No other cells adapt by altering inter-cellular connections

Question 2

Neuron / Action Potential Recap

Answer 2

Negatively charged ions produce inhibitory effect – prevent action potential

Action potential from depolarization

Axon terminals – pass impulse to neighboring cell

Electrical signal becomes a chemical signal through neurotransmission

Psychotropic medications alter these processes
*drugs have effects on pathways

Question 3

Neuroplasticity

Answer 3

Brain learns which connections to strengthen, develops pathways

Reroute pathway, reform function = plasticity through protein synthesis–learning

Nerve cells are constantly adapting, very gradual
Similar to photokinesis, leaves turn to face the light
• e.g. time needed after stroke to regain functionality– new neural connections to replace those are destroyed

Question 4

Pruning

Answer 4

Dendrites and axon branches are continuously removing old connections and establishing new connections with neighboring cells

Begins soon after birth continues throughout life
Dramatic pruning increases in late adolescence

Some evidence that pruning process may precipitate emergence of SZ

Question 5

Terminating Neurotransmission: Diffusion

Answer 5

NT molecules drift outside synapse altogether into extracellular space

No receptors to bind with, eventually metabolized

Question 6

Terminating Neurotransmission: Deactivation in Synapse

Answer 6

e.g. MAO

e.g. COMPT
• Cutting atoms from ends of NT molecule
• Can’t fit in lock-and–key to dendrite

Question 7

Terminating Neurotransmission: Negative feedback

Answer 7

NT binds to autoreceptor on pre-synaptic neuron which signals the shut off of NT release

Question 8

Terminating Neurotransmission: Reuptake

Answer 8

Reuptake sites on presynaptic membranes
→5HT transporter proteins

Specific to each type of NT, each has its own proteins for reuptake
o “like little mini hoover vacuum cleaners” that retrieve neurotransmitter from the synapse

Return NT to presynaptic vesicles for reuse

Question 9

Terminating Neurotransmission: Deactivation inside axon terminal

Answer 9

After the NT molecules are returned to the neuron by transporter reuptake proteins, they have a brief moment of freedom

They are unprotected in the neuron, haven’t been recaptured yet by the vesicle

They are quickly gathered and stored within the vesicle, protected and held for future use

→but during that brief interval, NT is vulnerable to deactivation by MAO

Question 10

Common NT’s in brain that we know of

Answer 10

5HT
Norepinephrine
Dopamine
→–most drugs work on these systems
*there are different subtypes of receptors for each NT
o e.g. 14 different subtypes of 5HT receptors

Also:
GABA
Cannabinoids
Glutamate
Acetylcholine

Neuropeptides—different class, we don’t know too much about

Opiate peptides: Naturally occurring opiates in the brain that interact with the opiate receptors
o Heroin
o Morphine
o Many others

Melatonin – neural hormone created by pineal gland
o circadian rhythms
o sleep regulation

Question 11

2nd Messenger System

Answer 11

2nd messenger = protein that carries signal inside postsynaptic neuron after NT binds to a postsynaptic receptor

Eventually leads to signal transduction, potentially changing the chemical makeup of the neuron, how it responds
*very complicated and very poorly understood

Receptor occupancy happens immediately

• bx and emotional changes take time
• may explain delayed clinical effect of psychotropic medications (e.g. 6 weeks Prozac)

G proteins, specific type of 2nd messenger linked to DA receptors

Question 12

Partial Agonism

Answer 12

“3rd generation” AP’s (Abilify, Buspar)

Not as effective as natural NT
*Weak agonist at low levels of naturally occuring NT’s

• Works like antagonist when high ocurring NT’s, but doesn’t stimulate as much as a naturally ocurring NT
• Net effect based on naturally occurring levels

Question 13

Receptors, general

Answer 13

Receptors are dynamically frequently changing entities, with variability in:

Amount of receptors available

Sensitivity

Number of receptor sites

Density

Binding capacity

Question 14

Downregulation

Answer 14

Agonistic drugs increase the action on a receptor

Neuron compensates:
*expressing fewer receptors on its membrane or *decreases binding efficacy

Result: receptors become less sensitive to medication

Question 15

Upregulation

Answer 15

Antagonist decreases receptor binding to NT

Body responds by producing more receptors and increases binding efficiency to counter the lower neurotransmitter levels→ homeostasis

Question 16

Stopping Neurotransmission

Answer 16

Turning off neurotransmitter release once neurotransmitters are in the synapse

Successful communication between neurons requires both stimulation and then stopping stimulation:

→you can’t just have a continuously stimulated postsynaptic neuron

Question 17

Excitotoxicity

Answer 17

Neural damge / death from excessive stimulation by GLU and similar substances.

GLU receptors are overactivated by glutamatergic storm

Question 18

Upregulation: Haldol

Answer 18

Chronic use results in massive dopamine blockade

Body responds by upregulating in nigrostriatal pathway

Neurons become abnormally sensitive
→ any amount of dopamine causes them to fire which can result in spasmodic, abnormal motor bx