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l13 Flashcards

1
Q

what do epileptic treatments look to enhance

A

GABA transmission to treat convulsions and seizures

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2
Q

what are the main neuronal types

A

Projection neurons-for GLU

Local interneurons-GABA

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3
Q

LOOK AT SLIDE 7

A

LOOK AT IT

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4
Q

2 main families of GABA receptor

A

GABA (A) ionotropic receptors
fast IPSPs
GABAergic

GABA (B) metabotropic receptors
G protein coupled receptors
indirectly coupled to K+ or ca2+
Both pre and post synaptic

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5
Q

Describe GABA (A) receptors structure

A

2 a + 3 more subunits

Heteropentameric

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6
Q

Describe GABA (A) receptors function

A

Cl- channel gated by the binding of 2 agonist molecules

Cl- potential is near RMP
Increasing chloride permeability

Hyperpolarizes the neuron

Decreasing depolarising effect of excitatory neuron

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7
Q

Give an example of a direct agonist and antagonist of GABA(A)

A

Muscimol- agonist

Bicuculline-antagonist

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8
Q

Give an example of an indirect agonist of GABA(A) channel

A

Benzodiazepine - binding increases the receptor affinity for GABA - increase frequency of channel opening
- anxiolytic and hypnotic drugs with rapid onset, but less satisfactory in the long term

Barbiturates increase the duration of channel openings 	(anaesthesia, epilepsy treatment)

Alcohol - agonist

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9
Q

GABA(A) Receptor- benzodiazepine action: where does it bind

A

a subunit

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10
Q

GABA(A) Receptor- benzodiazepine action: function

A

Indirect agonist - benzodiazepine binds to a subunit, changes conformation of the receptor so GABA activation of receptor is more effective.

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11
Q

What are the effects of benzodiazepine

A 
reduce anxiety
cause sedation
reduce convulsions
relax muscles
cause amnesia
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12
Q

what do inverse agonists that bind to benzodiazepine site do?

A

– produce anxiety and predisposition to convulsions

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13
Q

GABA(A) Rs - barbiturates and alcohol- effect?

A

Both have same effect: to enhance GABA(A) activity and effects are additive - combining the two can be fatal

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14
Q

What does alcohol also interact with

A

NMDA, glycine, nicotinic and serotonin

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15
Q

what do low doses of alcohol as well as high doses do

A

Low doses of alcohol - mild euphoria and anxiolytic effects

Higher doses - incoordination, amnesia

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16
Q

what is an agonist for GABA(B) receptor -metabotropic

A

Baclofen

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17
Q

What is baclofen used to treat

GABA(B) receptor -metabotropic

A

used as a muscle relaxant to reduce spasticity e.g. in Huntington’s disease

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18
Q

When activated what does the Gi subunit do

GABA(B) receptor -metabotropic

A

Inhibits adenylyl cyclase

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19
Q

when activated what does the Gby gated K+ channels do

A

Increase K+ conductance

decreases ca2+ conductance-presynaptically

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20
Q

What is another phrase for Slow hyperpolarizing current

A

(late inhibitory postsynaptic potential)

IPSP’s

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21
Q

What are the main overall function of glutamate neurons

A

primary route of sensory and motor information and relay neurons between brain areas

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22
Q

Overall main function of GABA neurons

A

interneurons, maintain balance between excitation and inhibition

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23
Q

In a neuron there are Specific populations of neurons that project diffusely and modulate the activity of Glutamate and GABA neurons in their target areas, what are they called

A

Diffuse modulatory systems

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24
Q

Give an example of some diffuse modulatory systems

A 
Dopaminergic (DA)
Serotonergic (5-HT)
Noradrenergic (NA/NE) 
Adrenergic
Cholinergic (ACh)
Histaminergic
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25
what are the 4 types of patterns of communication in the NS
Point-to-point systems Hormones released by the hypothalamus ANS neurons activating body tissues Diffuse modulatory system with divergent axonal projections (not classical synapse)
26
In the dopaminergic system, where are the cell bodies and where do they project to?
Cell bodies in the midbrain Project into the forebrain
27
what is the Nigrostriatal system responsible for
motor control
28
what is the Mesocortical system | responsible for
behavioural effects
29
what is the Tuberohypophyseal system responsible for
endocrine control
30
Dopamine (DA) receptors Dopamine produces both EPSP's and IPSPS depending on what factor, and after which have been activated
Depending on receptor sub type and Coupled G proteins D1-like (1 & 5) Gs - stimulate adenylyl cyclase - stimulate phospholipase C postsynaptic ``` D2-like (2, 3 & 4) Gi - inhibit adenylyl cyclase - open K+ channels - close Ca2+ channels postsynaptic presynaptic autoreceptors (D3) ```
31
Dopamine (DA) receptors where do the cell bodies of neurons in the Nigrostriatial system reside in and project to
cell bodies in the substantia nigra project to the striatum (caudate nucleus
32
what is a dysfunction of the dopaminergic system
Parkinson’s disease destruction of DA projections from SN to basal ganglia Huntington’s disease destruction of DA target neurons in striatum
33
what drugs are used to treat such dopaminergic dysfunctions
L-DOPA, Monoamine oxidase (MAO) inhibitors, Dopamine receptor agonists -treatments for Parkinson’s Disease
34
dopaminergic system where do the cell bodies of the Mesolimbic system reside in and to where do they project
cell bodies in ventral tegmental area (VTA) project to the limbic system, nucleus accumbens
35
what is the role of the Mesolimbic system
It has a role in reinforcement (reward) of several categories of stimuli, including drugs of abuse
36
what is a dysfunction of the mesolimbic system
Addiction - most drugs of abuse lead to enhanced DA release in the NAcc
37
Give an example of drugs that affect the Mesolimbic system The dopaminergic system
Cocaine and Amphetamine
38
ST effects of Cocaine and Amphetamine
- give the feeling of increased alertness and self confidence, a sense of exhilaration and euphoria and a decreased appetite. - large doses can cause stereotypy and psychosis
39
LT effects of Cocaine and Amphetamine
- natural rewards, e.g. water, food, sex increase DA transmission and leads to reinforcement of associated behaviours - increased DA by cocaine etc. short circuits pathway, drug taking behaviours become reinforced
40
The dopaminergic system Where do cell bodies of the mesocortical system lie and to where do they project
VTA projections to prefrontal cortex
41
What is the function of the mesocortical system
Role in functions such as working memory and planning
42
what is a dysfunction of the mesocortical system
Schizophrenia
43
what drugs can be used to treat Schizophrenia & effects
Typical antipsychotics (e.g. chlorpromazine and haloperidol) - DA receptors antagonists (pre and postsynaptic) - Increase DA turnover - lose autoreceptor inhibiton - Blockade of postsynaptic receptors - upregulation
44
what are the Extrapyramidal side effects of the Antipsychotic drugs
tardive dyskinesia etc. | (chronic blockade causes system to become supersensitive
45
give an example of an atypical antipsychotic & effects
Clozapine - antagonist of D4 receptors (cortex only) Reduce psychosis associated with schizophrenia Antipsychotic effects without EPS
46
describe the serotonergic system
Nine raphe nuclei in reticular formation with diffuse projections -each projects to a different part of the brain
47
serotonergic system has an ascending?
Reticular activating system
48
serotonergic system Dorsal and medial raphe projects to where?
through-out the cerebral cortex
49
when do raphe neurons fire
They fire tonically during wakefulness and are quiet during sleep
50
where are raphe neurons
they lie to either side of the midline of the brain stem.
51
what is the main functions of the Serotonergic system
mood sleep pain emotion appetite
52
what are the drugs with general effects on serotonergic system
Selective Serotonin Reuptake inhibitors-Fluoxetine (Prozac) -which increase serotonin function by preventing its uptake treatment for depression and anxiety disorders but depression not a simple case of low serotonergic tone (effects not seen for 2-3 weeks LSD- hallucinogen Causes a dreamlike state with altered sensory perceptions- potent agonist at 5HT1A receptors in raphe nucleusnsory perceptions-
53
serotonergic system what does MDMA (Ecstasy do )
``` causes serotonin (and norepinephrine) transporters to run in reverse increased release of serotonin and blocked reuptake ```
54
Noradrenergic System where do they project to
Projections form the Locus Coeruleus throughout the brain
55
what is the function of the Noradrenergic System
Role in arousal and attention
56
what type of receptors are in the Noradrenergic system
Metabotropic receptors
57
what subunits do the alpha and beta adrenergic receptors correspond to
a1 Gq a2 Gi b1, 2 and 3 Gs
58
Adrenergic system and project towards
Primarily in lateral tegmental area, projecting to thalamus and hypothalamus.
59
Cholinergic system from where do the cell bodies lie and synapse with...
Acetylcholine at NMJ and | synapses in the autonomic ganglia
60
In the Basal Forebrain complex where is cholinergic innerv
Hippocampus and the neocortex
61
Cholinergic system In the brain stem complex, where is cholinergic innerv
innervates the dorsal thalamus and telencephalon
62
Cholinergic system what is the brain stem complex
innervates the dorsal thalamus and telencephalon -control excitability of sensory relay neurons and provide a cholinergic link between the brain stem and basal forebrain complex
63
4 functions of ACH
Skeletal NMJ Neuromuscular synapse between the vagus nerve and cardiac muscle fibers Synapses in the ganglia of the visceral motor system
64
Look at slide 30
LOOK AT IT!!!!!!!!!!
65
Disorders of the cholinergic system -peripheral
Myasthenia gravis | Autoimmune disease - destroys cholinergic receptors in the muscle - muscle weakness and eventual loss of muscle activity
66
Disorders of the cholinergic system -Brain
Alzheimer’s disease Loss of cholinergic neurons in the basal ganglia - possibly underlies deficits in memory associated with the disease. Addiction: nicotine addiction Epilepsy Autosomal dominant nocturnal frontal lobe epilepsy (ADNFLE) associated with mutations in nicotinic receptor genes. Other psychiatric disorders Comorbidity with smoking
67
ACHesterase inhibitors treat what diseases and give examples
Alzheimers disease-physostigmine Myasthenia gravis-neostigmine
68
what does botox do
Prevents release of ACH at NMJ
69
What does latrotoxin do
Permanent rlease-depletes ACh at NMJ
70
what are the 2 types of ACH receptor:
Muscarinic Nicotinic
71
What types of receptors are muscarinic and nicotinic
Metabotropic Ionotropic
72
what pathway do M3 receptors use
Via Gq to phosphatidylinositol
73
where are M5 receptors found
Smooth muscles and glands
74
what pathway do M4 receptors use
Via Gi to inhibit cAMP
75
Where are M4 receptors used
Smooth muscles and cardiac muscles
76
what is the result of the activation of M-type receptors
Hyperpolarisation or depolarisation due to opening or closing of K+, ca2+ or cl- channels
77
what is the function of the histaminergic system
Arousal & attention Reactivity of vestibular system Mediation of allergic responses Influence of brain blood flow
78
what type of receptors are in the Histaminergic system
3 G-protein-coupled Rs

202:theme 1 (8 decks)

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