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Principles of Med Neuroscience > L.8 > Flashcards

L.8 Flashcards

1
Q

What are the three types of ionotropic glutamate receptors?

A
  • NMDA receptors
  • AMPA receptors
  • Kainate receptors
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2
Q

What is the agonist for NMDA receptors?

A

NMDA

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3
Q

What is the antagonist for NMDA receptors?

A

APV drug

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4
Q

What is the agonist for AMPA receptors?

A

AMPA

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5
Q

What is the antagonist for AMPA receptors?

A

CNQX drug

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6
Q

What is the agonist for Kainate receptors?

A

Kainaic acid

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7
Q

What is the antagonist for Kainate receptors?

A

CNXQ drug

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8
Q

Outline how Non-NMDA Receptors work?

A
  1. gluatamte binds to Non-NMDA receptor (activates them)
  2. when receptors are activated –> ion channels open
  3. Na+ flow in and K+ flow out
  4. Na+ influx (more positive)
  5. EPSP
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9
Q

Outline how NMDA receptors work

A
  1. glutamate & glycine must bind to NMDA receptor
  2. Mg2+ blocks receptor at resting state
  3. neuron needs to be depolarised to removed Mg2+
  4. Once Mg2+ is removed, NMDA receptors open = Ca2+ in and K+ out
  5. Ca2+ acts as secondary messenger causing intracellular processes
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10
Q

What is the role of NMDA receptors in LTP?

A
  • Ca2+ influx is important for synaptic plasticity & long-term potentiation (learning & memory)
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11
Q

What is late EPSP in NMDA receptors

A
  • open more slowly + stay open for longer
  • allows a longer-lasting signal
  • good for synaptic plasticity & LTP
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12
Q

TRUE or FALSE: NMDA receptors are metabotropic (+ why)

A
  • FALSE (ionotropic)
  • they don’t use G-coupled proteins
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13
Q

TRUE or FALSE: Non-NMDA receptors are early-phase EPSP

A

TRUE

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14
Q

What is the result of too little GABA in the nervous system?

A

Seizures or muscle spasms due to lack of inhibitory control

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15
Q

What happens when there is too much GABA?

A

Loss of consciousness and coma

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16
Q

What is the function of the GABAergic system?

A

Inhibitory signaling to prevent over-excitation

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17
Q

What are the 2 main consequences of NMDA receptors dysregulation

A
  • Schizophrenia
  • glutamate excitotoxicity
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18
Q

What is glutamate excitotoxicity

A

too much glutamate overstimulates neurons

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19
Q

What causes glutamate excitotoxicity to happen

A
  • NMDA receptors are overactivated
  • excess Ca2+ influx
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20
Q

What are the effects of glutamate excitotoxicity

A
  • cell damage
  • stroke
  • seizures
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21
Q

How can NMDA receptors cause Schizophrenia effects

A
  • NMDA receptors are inhibited by PCP
  • causes hallucinations like in Schizophrenia
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22
Q

What are the 2 main types of GABA receptors

A
  • GABA ionotropic receptors (GABA A)
  • GABA metabotropic receptors (GABA B)
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23
Q

What are the features of GABA ionotropic receptors

A
  • ligand-gated Cl- channels
  • fast/early IPSP
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24
Q

What are the features of GABA metabotropic receptors

A
  • G-protein coupled receptors
  • slow/late IPSP
  • K+ and Ca2+
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25
Q

What happens when two GABA or agonist molecules bind to a GABA receptor?

A

Cl- channels open

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26
Q

What is the result of Cl⁻ flowing into a neuron?

A

Hyperpolarization and decreased excitability.

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27
Q

How does the opening of Cl⁻ channels affect excitatory signals?

A

reduces the effect of excitatory signals

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28
Q

What is the effect of Muscimol on GABA receptors?

A
  • direct agonist
  • mimics effect of GABA
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29
Q

What is Bicuculline’s role at the GABA receptor?

A
  • direct antagonist
  • blocks/reduces effect of GABA
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30
Q

How do indirect agonists enhance GABAergic activity?

A

they enhance GABAergic activity without binding to the GABA-binding site

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31
Q

How do benzodiazepines affect GABA receptors?

A
  • increases receptor’s affinity for GABA
  • increasing the frequency of channel openings
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32
Q

What are the effects of benzodiazepines?

A
  • relaxes muscles
  • reduces anxiety
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33
Q

How do barbiturates affect GABA receptors?

A

They increase the duration of channel openings when GABA binds

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34
Q

What are the clinical uses of barbiturates?

A
  • anaesthesia
  • epilepsy treatment
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35
Q

How does alcohol act on GABA receptors?

A

Alcohol acts as an agonist at GABA receptors

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36
Q

What effects are seen with low doses of alcohol?

A
  • Mild euphoria
  • anxiolytic effects (reduces anxiety)
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37
Q

What effects are seen with higher doses of alcohol?

A

incoordination and amnesia

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38
Q

What type of protein are GABA metabotropic receptors coupled to?

A

Gi

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39
Q

What effect does the activation of Gi proteins have on adenylyl cyclase in GABA metabotropic receptors?

A

It inhibits adenylyl cyclase

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40
Q

How does the activation of GABA metabotropic receptors affect potassium (K+) channels?

A

It activates K+ channels

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41
Q

What is the result of K+ channel activation in GABA metabotropic receptors?

A

Hyperpolarization, leading to a late inhibitory post-synaptic potential

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42
Q

What is the therapeutic use of baclofen, which binds to GABA metabotropic receptors?

A

It helps relax muscles and reduces spasticity

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43
Q

What is the role of glutamate neurons

A

primary route for sensory and motor information and relay between brain areas

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44
Q

What is the role of GABA neurons

A

act as interneurons, maintaining a balance between excitation and inhibition

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45
Q

What neurotransmitter is involved in the dopaminergic system?

A

dopamine

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46
Q

How many major pathways are in the dopaminergic system and what are their names?

A
  • Nigrostriatal
  • Mesolimbic
  • Mesocortical
  • Tuberoinfundibular
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47
Q

What is the main function of the Nigrostriatal Pathway?

A

motor control (movement)

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48
Q

Where does the Nigrostriatal Pathway project from and to?

A

From the substantia nigra to the striatum

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49
Q

What diseases are associated with dysfunction in the Nigrostriatal Pathway?

A
  • Parkinson’s Disease
  • Huntington’s Disease
50
Q

What happens to dopamine neurons in Parkinson’s disease?

A

destruction of dopamine projections from the substantia nigra to the basal ganglia

51
Q

What happens to dopamine neurons in Huntington’s disease?

A

destruction of dopamine neurons in the striatum

52
Q

What treatments are used for diseases associated with the Nigrostriatal Pathway?

A
  • L-Dopa
  • MOA inhibitor
  • dopamine receptor agonist
53
Q

How does L-DOPA work in treating Parkinson’s disease?

A

It converts into dopamine in the brain

54
Q

What is the role of MAO inhibitors in treating dopaminergic dysfunction?

A

They prevent the breakdown of dopamine

55
Q

What do dopamine receptor agonists do?

A

They mimic dopamine by stimulating dopamine receptors

56
Q

What is the Mesolimbic Pathway?

A

Dopamine projections from the ventral tegmental area (VTA) to the nucleus accumbens

57
Q

What are the primary functions of the Mesolimbic Pathway?

A

Rewards, motivation, and addiction (reward system)

58
Q

What behaviour is associated with dysfunction in the Mesolimbic Pathway?

A

addictive behaviour

59
Q

How do drugs affect the Mesolimbic Pathway?

A
  • Drugs hijack the reward system by causing excess dopamine release
  • reinforce behaviour and cravings
60
Q

What are examples of drugs that enhance dopamine release in the Mesolimbic Pathway?

A

Cocaine and amphetamine

61
Q

What are the immediate effects of drugs like cocaine and amphetamines?

A
  • increased alertness
  • heightened self-confidence
62
Q

What physical effects do drugs in the Mesolimbic Pathway mimic?

A

Sympathetic nervous system activation:
- increased heart rate
- increased blood pressure
- dilation of pupils

63
Q

What happens to dopamine transmission with long-term drug use?

A

Eating, drinking, and sexual activity increase dopamine transmission, reinforcing these behaviours

64
Q

How do cocaine and amphetamines affect long-term dopamine levels?

A

They increase dopamine in pathways, reinforcing drug-taking behaviours

65
Q

What is the consequence of long-term dopamine stimulation by drugs?

A

Downregulation of dopamine receptors, leading to cravings for the drug

66
Q

What is the Mesocortical Pathway

A

Dopamine projections from the ventral tegmental area (VTA) to the prefrontal cortex

67
Q

What are the primary functions of the Mesocortical Pathway?

A

Cognition, including planning, working memory, and learning

68
Q

What dysfunction is associated with the Mesocortical Pathway?

A

Psychosis, such as schizophrenia

69
Q

How does dysfunction in the Mesocortical Pathway affect schizophrenia?

A

It causes a lack of dopamine, leading to negative symptoms (things missing in behaviour/emotions)

70
Q

What are negative symptoms

A

Behaviours and emotions that are reduced or missing compared to a healthy person

71
Q

What treatments are used to treat dysfunctions in the mesocortical pathway?

A

Typical antipsychotics and atypical antipsychotics

72
Q

What do typical antipsychotics like Chlorpromazine and Haloperidol do in the brain?

A

They block dopamine receptors

73
Q

How does the brain respond to typical antipsychotics blocking dopamine receptors?

A

It increases the number of dopamine receptors (upregulation), making the brain more sensitive to dopamine

74
Q

What are the side effects of typical antipsychotics?

A

Increased sensitivity to dopamine, which can lead to motor control side effects

75
Q

How are atypical antipsychotics like Clozapine different from typical antipsychotics?

A

They target specific dopamine receptors and have fewer motor control side effects

76
Q

What is the tuberoinfundibular pathway

A

Dopamine projections from the hypothalamus to the pituitary gland

77
Q

What is the function of the tuberoinfundibular pathway?

A

It is involved in endocrine control

78
Q

How does dopamine affect neurons?

A
  • can produce excitatory signals (EPSP)
  • can produce inhibitory signals (IPSP)
79
Q

What is the effect of D1 dopamine receptors on neurons?

A

They lead to excitation (EPSPs), increasing neuronal excitability

80
Q

Which G protein is coupled with D1 receptors?

A

Gs protein

81
Q

How do D1 receptors increase neuronal excitability?

A
  • By stimulating adenylyl cyclase and phospholipase C
  • leading to excitatory postsynaptic potentials
82
Q

What is the effect of D2 dopamine receptors on neurons?

A

They lead to inhibition (IPSPs), decreasing neuronal excitability.

83
Q

Which G protein is coupled with D2 receptors?

A

Gi protein

84
Q

How do D2 receptors decrease neuronal excitability?

A
  • By inhibiting adenylyl cyclase
  • opening K+ channels
  • closing Ca2+ channels
85
Q

What is the effect of opening potassium channels through D2 receptor activation?

A

It hyperpolarizes the neuron, making it less excitable

86
Q

What is the effect of closing calcium channels through D2 receptor activation?

A

It decreases calcium influx, which inhibits excitatory signals

87
Q

Why is the balance between D1 and D2 receptor systems important?

A

It helps maintain dopaminergic tone in the brain

88
Q

What conditions can arise from disruptions in the balance between D1 and D2 receptors?

A
  • Parkinson’s disease
  • schizophrenia
  • addiction
89
Q

What are the two main pathways of serotonin projections from the Raphe nuclei?

A
  • Ascending pathway
  • descending pathway
90
Q

Describe the descending serotonergic pathway

A

serotonin projections from the Rpahe nuclei to spinal cord and cerebellum

91
Q

Describe the ascending pathway of serotonergic system

A

serotonin projections from the raphe nuclei to cortex and limbic system

92
Q

What are the primary functions of the serotonergic system?

A

Mood regulation, sleep, pain, emotion, and appetite control

93
Q

What are the consequences of dysfunction in the serotonergic system?

A

Depression and anxiety disorders

94
Q

What is the overall cause of depression

A

low serotonin levels

95
Q

What is the overall cause of anxiety disorders

A

serotonin imbalance

96
Q

What are Selective Serotonin Reuptake Inhibitors (SSRIs) and how they work?

A

medications that treat depression and anxiety disorders by increasing serotonin function by blocking its reuptake

97
Q

give an example of SSR

A

fluoxetine/Prozac

98
Q

What effects does LSD have on the serotonergic system?

A

LSD acts as a potent agonist at 5HT1A receptors in the raphe nucleus and 5HT2A receptors in the prefrontal cortex, leading to altered sensory perceptions and hallucinogenic properties

99
Q

Why is depression considered complex regarding serotonin levels?

A

Depression is not simply due to low serotonin

100
Q

What is the pathway for noradrenaline projections in the noradrenergic system?

A

from the lateral coeruleus and project to the thalamus and hypothalamus

101
Q

What is another way to write serotonin

A

5HAT

102
Q

What neurotransmitter is primarily associated with the noradrenergic system?

A

Norepinephrine (noradrenaline)

103
Q

What are the key functions of the noradrenergic system?

A
  • attention
  • stress response
  • mood
  • autonomic functions
  • cognition
104
Q

What are the two types of metabotropic receptors in the noradrenergic system?

A
  • Alpha-adrenergic receptors
  • Beta-adrenergic receptors
105
Q

What is the function of Alpha-adrenergic receptors

A

smooth muscle contraction

106
Q

What is the function of Beta-adrenergic receptors

A

relaxation of smooth muscles

107
Q

What dysfunctions are associated with the noradrenergic system?

A
  • anxiety
  • depression
  • stress-related disorders
108
Q

How does overactivity of the noradrenergic system affect a person?

A

leads to excessive release of noradrenaline, which can result in anxiety

109
Q

What happens when there is underactivity in the noradrenergic system?

A

a lack of noradrenaline, which can contribute to various mood disorders

110
Q

What are beta blockers, and how do they function in the noradrenergic system?

A

Beta blockers block beta receptors, leading to reduced heart rate and calming the body’s response to stress (e.g., used in anxiety

111
Q

How do noradrenaline reuptake inhibitors (anti-depressants) work as a treatment?

A

They increase the levels of noradrenaline in the brain, improving mood and energy (ex: depression)

112
Q

In which nervous systems does the cholinergic system operate?

A

PNS and CNS

113
Q

What role does acetylcholine (ACh) play at the neuromuscular junction?

A

ACh facilitates communication between motor neurons and skeletal muscles, leading to muscle contraction

114
Q

How does ACh function in autonomic ganglia?

A

ACh is involved in the sympathetic and parasympathetic systems, regulating functions such as heart rate and digestion

115
Q

What are the cholinergic projections in the basal forebrain complex?

A

from the medial septal nucleus and the nucleus basalis to the hippocampus and cortex

116
Q

What are the names of 2 cholinergic pathways in the CNS

A
  • basal forebrain complex
  • brainstem complex
117
Q

Where do the 2 cholinergic pathways in the PNS work

A
  • neuromuscular junction
  • autonomic ganglia
118
Q

What is the primary function of the cholinergic pathways in the basal forebrain complex?

A

memory and cognition

119
Q

What effect does the loss of ACh neurons in the basal forebrain complex have on memory?

A
  • memory deficits
  • Alzheimer’s disease
120
Q
A

Principles of Med Neuroscience (6 decks)

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