Neurotransmitter Systems Flashcards
1
Q
Neuronal communication is…
A
- chemical
- electrical
2
Q
chemical neuronal communication
A
- Primarily the result of two ions, sodium (Na+) and potassium (K+)
- Ions move into or out of the cell, but not freely
3
Q
electrical neuronal communication
A
- 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
4
Q
chemical gradients
A
Ions want to flow from high concentration to low concentration (like dye in water)
5
Q
electrical gradients
A
- 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
6
Q
cell membrane
A
- guardian
- Lipid bilayer is tightly packed, both hydrophobic and hydrophilic, keeping out all dangerous entities
7
Q
channels and pumps
A
- 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
8
Q
sodium-potassium pump
A
- 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
9
Q
how does sodium-potassium pump affect chemical and electrical gradient?
A
- 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)
10
Q
potassium channels
A
- 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
11
Q
cell polarization
A
- 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)
12
Q
receptors
A
- Receptors determine signal, not NTs
- receptor types:
- ionotropic (channels)
- metabotropic (signalling proteins)
13
Q
ionotropic receptors
A
- AKA ligand-gated ion channels (ligand is aka NT)
- Excitatory (depolarize)
- Inhibitory (hyperpolarize)
- Fast, transient effect
14
Q
metabotropic receptors
A
- AKA G-protein-coupled receptors
- Modulate cell
- Modulate signals
- Slow, longer lasting effect
- Cause signal cascades
15
Q
receptor locations
A
- Postsynaptic
- Presynaptic
- Autoreceptors (dampen signal)
- Heteroceptors (modulate signal – “turn volume up or down”)
16
Q
drug types
A
- Agonist (increases specific NT system)
- Antagonist (decreases specific NT system by binding to it)
- Other (e.g. transporter blocker, reuptake inhibitor, enzyme inhibitor)
17
Q
glutamate
A
- 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)
18
Q
drugs: glutamate antagonists
A
- 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)
19
Q
GABA
A
- Primary inhibitory neurotransmitter
- Used throughout brain
- Ionotropic and metabotropic
- Again, not a great target for drugs (used all across the brain)
20
Q
drugs: GABA agonists
A
- Benzodiazepines
- Ethanol
- Chloroform
- Ether
- Similar sedative effects as glutamate antagonists (GABA antagonists would increase spontaneous activity across the brain)
21
Q
the amines
A
- 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
22
Q
dopamine and Parkinson’s disease
A
- 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
23
Q
Olds and Milner: theory about motivation for brain stimulation
A
- 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
24
Q
addictive drugs and dopamine
A
- All addictive drugs directly or indirectly increase dopamine transmission
- Amphetamine, cocaine, heroin, nicotine, oxycodone, ethanol, etc.
25
Q
Schizophrenia medications
A
- 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)
26
Q
Salamone: separating pleasure from motivation
A
- 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
27
Q
norepinephrine
A
- Originates in brain stem region called the locus coeruleus
- Enhances memory by stress/emotion
28
Q
Potential PTSD treatment
A
- “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
29
Q
serotonin
A
- 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
30
Q
selective serotonin reuptake inhibitors
A
- 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?)
31
Q
endocannabinoids
A
- 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)
32
Q
adenosine
A
- 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
33
Q
acetylcholine
A
- Important in neuromuscular junction -> how we initiate movement
- Also important for basal forebrain
- Involved in wakefulness, attention, etc.
- Acetylcholine agonist = nicotine (increases alertness)
