Neuromodulation 1 Flashcards Preview

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Flashcards in Neuromodulation 1 Deck (11):
1

Primary neurotransmission

Glutamate and GABA - the main workhorses of the brain

2

Neuromodulation

Affect the response properties of a neuron
-do not carry primary information themselves.

e.g. dopamine, serotonin, noradrenaline, acetylcholine

3

The Diffuse Modulatory Systems

Dopamine - movement /reward
Serotonin - sleep / mood
Noradrenaline - arousal / attention
Acetylcholine - attention / learning

4

Regulation of neurotransmitter synthesis and release

1) Neurotransmitter is synthesized in cell body
2) Neurotansmitter is packaged into vesicles
3) N is released when vesicles fuse
4) Neurotransmitter binds to and activated postsynaptic receptors
5) N diffuses away and is metabolised and/or transported back into the terminal.

5

Ionotropic

Ligand-gated ion channels
Direct transmission
Flux ions directly
Excitatory or inhibitory
Fast transmission of information

6

Metabotropic

G protein coupled receptors
Modulatory
May lead to ion flux indirectly
(G protein-gated/ phosphorylation- gated ion channels)
Excitatory or inhibitory
Slower (but prolonged / amplified transmission) of informati

7

Activation of Metabotropic receptors

Transmitter (ligand) binds to extracellular
domain of receptor
- conformational change in
intracellular domain
- triggers uncoupling of
a heteromeric G protein
on the intracellular surface
- the signal is transduced across
the cell membrane

8

Kinases and phosphatases

activity of many proteins regulated by their phosphorylation state
maintenance of phosphorylation state an important level of control

9

The opioidergic system

Endogenous opioids – neuropeptide transmitters

Act at opioid/opiate receptors (metabotropic)
agonists – opiates, e.g. morphine, heroin
antagonists – naloxone, naltrexone
Roles:
Analgesia
e.g. Stress induced analgesia – release of endogenous opioids inhibits pain signals reaching the brain (can block with antagonist drugs)
Relaxation - regulating noradrenaline release

10

Opiate use

Subjective effects:
Euphoria and intense rush with heroin compared to morphine due to route of administration and entry to brain (seconds vs minutes)

Relaxing effects – inhibition of noradrenergic pathways

Tolerance / dependence
Increasing doses needed to get analgesic response/euphoria

11

Tolerance to drug effects

Acute morphine - acutely inhibits firing of LC neurons
Chronic treatment - LC neurons return to their normal firing rates
Withdrawal - dramatic increase in LC firing