Neurotransmitter Systems

Question 1

Neuronal communication is…

Answer 1

• chemical

- electrical

Question 2

chemical neuronal communication

Answer 2

• Primarily the result of two ions, sodium (Na+) and potassium (K+)
• Ions move into or out of the cell, but not freely

Question 3

electrical neuronal communication

Answer 3

• Ions are positively and negatively charged (Na+ and K+ are both positive, as per “+”)
• As they move into or out of cell, they change the potential (voltage) at the membrane
• • Note: absence of positive is negative! i.e. remove a positive, leave a negative

Question 4

chemical gradients

Answer 4

Ions want to flow from high concentration to low concentration (like dye in water)

Question 5

electrical gradients

Answer 5

• Charge/potential wants to flow from high concentration to low concentration, too
• Sometimes electrical and chemical gradients are at odds, causing an equilibrium that =/= 0mV

Question 6

cell membrane

Answer 6

• guardian

- Lipid bilayer is tightly packed, both hydrophobic and hydrophilic, keeping out all dangerous entities

Question 7

channels and pumps

Answer 7

• If you want to get ions through lipid bilayer, you need channels and pumps
• Only certain molecules and ions permitted via channels and pumps
• • Channels: allow passive diffusion (i.e. along chemical gradient)
• • Pumps: actively push ions against their chemical gradient
• – Requires energy (ATP)
• In a cell with no channels or pumps, nothing moves into or out of the cell

Question 8

sodium-potassium pump

Answer 8

• Embedded in cell membrane
• Extremely important
• • Consumes 2/3rds of all neuronal energy!
• Pushes 3 Na+ out and 2 K+ in
• • i.e. Active process that requires energy

Question 9

how does sodium-potassium pump affect chemical and electrical gradient?

Answer 9

• chem: With sodium potassium pump, more sodium on the outside -> wants to move inside (and vice versa with potassium)
• elec: Voltage becomes more negative (absence of 3 positives leaves a negative – see image)

Question 10

potassium channels

Answer 10

• K+ can move freely via K+ channels that are always open
• Na+ cannot move freely across the membrane
• • It has channels, but they are usually closed

Question 11

cell polarization

Answer 11

• Na+/K+ pump pushing more Na+ out of cell than K+ into cell -> Result: inside of cell more negative than outside
• But K+ can move freely through its channels -> Result: K+ wants to move with chemical gradient, out of the cell
• But this moving K+ is making the cell even more negative -> Result: flow of K+ stops when force of electrical gradient equals force of chemical gradient
• End result: cell has resting membrane potential of ~-70mV (force of K+ wanting to move out equals force of electricity wanting to move in -> chemical driving force = electrical driving force)

Question 12

receptors

Answer 12

• Receptors determine signal, not NTs
• receptor types:
• • ionotropic (channels)
• • metabotropic (signalling proteins)

Question 13

ionotropic receptors

Answer 13

• AKA ligand-gated ion channels (ligand is aka NT)
• Excitatory (depolarize)
• Inhibitory (hyperpolarize)
• Fast, transient effect

Question 14

metabotropic receptors

Answer 14

• AKA G-protein-coupled receptors
• Modulate cell
• Modulate signals
• Slow, longer lasting effect
• Cause signal cascades

Question 15

receptor locations

Answer 15

• Postsynaptic
• Presynaptic
• • Autoreceptors (dampen signal)
• • Heteroceptors (modulate signal – “turn volume up or down”)

Question 16

drug types

Answer 16

• Agonist (increases specific NT system)
• Antagonist (decreases specific NT system by binding to it)
• Other (e.g. transporter blocker, reuptake inhibitor, enzyme inhibitor)

Question 17

glutamate

Answer 17

• Primary excitatory neurotransmitter
• Used throughout the brain
• Ionotropic (AMPA, NMDA, Kainate)
• Metabotropic (mGluR)
• Not a great target for drugs: Affects a lot of different processes (not very targeted; used everywhere)

Question 18

drugs: glutamate antagonists

Answer 18

• Barbiturates
• Nitrous oxide
• Ketamine
• Ethanol
• These antagonist drugs are depressants -> sedates you, slows you down (if the drugs were agonists, your brain would be overactive -> mania)

Question 19

GABA

Answer 19

• Primary inhibitory neurotransmitter
• Used throughout brain
• Ionotropic and metabotropic
• Again, not a great target for drugs (used all across the brain)

Question 20

drugs: GABA agonists

Answer 20

• Benzodiazepines
• Ethanol
• Chloroform
• Ether
• Similar sedative effects as glutamate antagonists (GABA antagonists would increase spontaneous activity across the brain)

Question 21

the amines

Answer 21

• All metabotropic (none act quickly)— play a modulatory role; not targeted – like a sprinkler system hitting many neurons at a time
• Dopamine
• Epinephrine (aka: Adrenaline)
• Norepinephrine (aka: Noradrenaline)
• Histamine
• Serotonin

Question 22

dopamine and Parkinson’s disease

Answer 22

• Main source: Substantia nigra pars compacta (SNc)
• By the time Parkinson’s symptoms show, 90% of dopamine receptors are dead (Results in difficulty in initiating movement)
• Dopamine replacement therapy possible through use of L-DOPA pills

Question 23

Olds and Milner: theory about motivation for brain stimulation

Answer 23

• Olds and Milner found that rats would continually press lever in order to receive brain stimulation to areas that produce dopamine -> Ventral Tegmental Area (VTA) to Nucleus Accumbens (NAcc)
• Olds and Milner believed it was pleasurable for them, but isn’t necessarily true

Question 24

addictive drugs and dopamine

Answer 24

• All addictive drugs directly or indirectly increase dopamine transmission
• Amphetamine, cocaine, heroin, nicotine, oxycodone, ethanol, etc.

Question 25

Schizophrenia medications

Answer 25

- Early schizophrenic drugs were dopamine antagonists, suggesting that they had overactive system - Even though they have higher dopamine levels, they don't have higher baseline pleasure (evidence against "pleasure/dopamine" belief)

Question 26

Salamone: separating pleasure from motivation

Answer 26

- Decision-making study with mice: Low effort, low reward vs. high effort, high reward - Post-training, all mice chose to put in high effort to get high reward - - Then given dopamine antagonists -> decreases motivation but not pleasure - - Dopamine has implications for motivation but not pleasure

Question 27

norepinephrine

Answer 27

- Originates in brain stem region called the locus coeruleus - Enhances memory by stress/emotion

Question 28

Potential PTSD treatment

Answer 28

- "reconsolidation" - Every time you tell a story/recall a memory, you're putting it into a fragile state (labile state) where it can be manipulated/changed - Treatment: blocking norepinephrine using norepinephrine antagonist/beta-blocker when recalling traumatic memory -> reduces emotional reaction to the memory

Question 29

serotonin

Answer 29

- Primarily from the raphe nuclei (brain stem) - Involved in mood, aggression, sociality, sleep, eating, etc. - Precursor: tryptophan -> can only cross the blood-brain barrier in the presence of carbs, if no carbs -> serotonin depletion

Question 30

selective serotonin reuptake inhibitors

Answer 30

- aka SSRIs, e.g. Prozac (fluoxetine) - Block serotonin from being removed from the synapse - Used for depression - Effects of SSRIs are quick, but improvements are slow - SSRI efficacy: - - Meta-analyses found that SSRIs are no better than placebo for mild to moderate depression - - May help with major depression, but important to keep regression to the mean in mind (is it the drug, or is it RTM?)

Question 31

endocannabinoids

Answer 31

- System is backwards: Travel from dendrite to axon, from post-synaptic to pre-synaptic - Weaken connection between two cells at a synapse (can lead to forgetting things)

Question 32

adenosine

Answer 32

- Remember: ATP is cellular energy (breaking bonds between phosphates produces the cellular energy) - Adenosine is ATP byproduct (what's left over after all phosphate bonds have been broken) - Adenosine makes you feel sleepy - Caffeine/theophylline are adenosine antagonists -> block adenosine receptors and prevents you from being sleepy

Question 33

acetylcholine

Answer 33

- Important in neuromuscular junction -> how we initiate movement - Also important for basal forebrain - - Involved in wakefulness, attention, etc. - Acetylcholine agonist = nicotine (increases alertness)