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Clinical neuroscience > L3 - Neurotransmitters > Flashcards

L3 - Neurotransmitters Flashcards

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1
Q

Role of glial cells

A

Support, nourish and insulate neurones whilst also removing waste

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2
Q

Types of glial cells

A

Astrocytes - most abundant
Microglial cells
Oligodendrocytes

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3
Q

Role of astrocytes

A 
Structural roles
Nutritional role - glucose - lactate shuttle 
Removes excess neurotransmitters 
Maintain ionic environment - K+ buffer 
Helps to form the blood brain barrier
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4
Q

Glucose transport into neurones

A

Directly - from the blood to the neurone through the interstitial space via GLUT1 and GLUT3

Indirectly - via glucose - lactate shuttle using astrocytes

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5
Q

Glucose - lactate shuttle

A
  1. Glucose from the blood is taken up by the astrocytes via GLUT1 and converted into glycogen for storage
  2. When the glucose demand in the neurone is high, glycogenolysis occurs where glycogen is converted to Pyruvate
  3. Pyruvate is then converted to lactate
  4. Lactate is transferred to the neurone via MCT1 and 2
  5. In the neurone, lactate is then converted to pyruvate where it can be used to produce ATP
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6
Q

How do astrocytes remove excess neurotransmitters

A

Via transporters
Astrocytes are abundant near synapses
Keeps extracellular neurotransmitter concentrations low to avoid exitotoxicity

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7
Q

Astrocyte K+ buffer

A

High neuronal activity increases ECF K+ concentration in the brain

Astrocytes take up K+ via:

  • NKCC2
  • Na+/K+ ATPase
  • Potassium channels
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8
Q

Cl- channels on astrocytes

A

Keep intracellular membrane potential in the astrocyte low so more K+ can diffuse in down the concentration gradient

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9
Q

Oligodendrocytes

A

Myelinated axon in the CNS

Many axons per oligodendrocytes

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10
Q

Microglia cells

A
  1. Recognise foreign material and become activated
  2. Phagocytose
  3. Antigen presenting cells to T cells
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11
Q

How are microglia cells activated

A
  1. Recognise foreign material
  2. Processes become thicker
  3. Form active phagocytic form
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12
Q

Blood brain barrier

A

Controls and limits the diffusion of substances from the blood to the brain ECF to maintain an optimum environment

Formed by endothelial cell tight junction and the basement membrane around capillaries mainly and astrocyte end feet processes partially

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13
Q

High intracellular K+

A

Causes depolarisation in surrounding neurones which leads to excess glutamate release.

Excess Ca2+ enters the neurone which causes exitotoxicity

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14
Q

What substances are transported across the blood brain barrier?

A

Free diffusion:

  • O2
  • CO2
  • H2O

Facilitated diffusion:

  • glucose
  • amino acids
  • sodium
  • potassium
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15
Q

Immune privilege

A
  • The brain does not undergo rapid rejection of allografts
  • CNS inhibits the initiation of the pro-inflammatory T cell response (specialised response)
  • prevents increase in intracranial pressure
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16
Q

Structure of a neurone

A

Cell soma - cell body
Dendrites - where axons synapse onto
Axon - carries action potentials
Presynaptic terminals - where neurotransmitters are released
Axon hillock - where action potential is propagated

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17
Q

Neurotransmitter release in synapses

A
  1. Action potential arises at the presynaptic terminal
  2. Voltage gates Ca2+ channels open allowing an influx of Ca2+
  3. Vesicles fuse with the presynaptic membrane and release the neurotransmitter
  4. The neurotransmitter diffuses across the synaptic cleft and bind to specific receptors on the postsynaptic membrane
  5. Ligand gated channels open allowing an influx of an ion
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18
Q

Factors affecting the postsynaptic response

A

Type of ligand gated ion channel or GPCR

Type of neurotransmitter

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19
Q

Types of neurotransmitters

A

Amino acids
Biogenic amines
Peptides

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20
Q

Examples of amino acid neurotransmitters

A

Glutamate
Glycine
GABA

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21
Q

Examples of biogenic amine neurotransmitters

A 
Acetylcholine
Noradrenaline
Dopamine
Serotonin 
Histamine
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22
Q

Examples of peptide neurotransmitters

A 
Substance P
Somatostatin 
Cholecystokinin 
Neuropeptide Y
Dynorphin
Enkephalins
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23
Q

Excitatory amino acid neurotransmitter

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A

Glutamate - most abundant neurotransmitter (70%)

24
Q

Inhibitory amino acid neurotransmitters

Study These Flashcards
A

Glycine - brainstem and spinal cord

GABA - brain

25
Types of glutamate receptors
Ionotropic | Metabotropic
26
Ionotropic glutamate receptors
AMPA - Na+/K+ Kainate - Na+/K+ NMDA - Na+/ K+ /Ca2+ - cause depolarisation and increases excitability
27
Metbotropic receptors
mGluR1-7 GPCR - G alpha q or G alpha i proteins
28
Fast excitatory response
- convergence of many synapses increases depolarisation - excitatory postsynaptic potential - depolarisation exceeding the threshold level of stimulation causes the propagation of action potentials
29
Glutamatergic synapses
Have AMPA and NMDA receptors
30
AMPA receptors
Mediate the initial fast depolarisation
31
NMDA
Dependent on AMPA for depolarisation as requires glutamate to bind and cell depolarisation to allow ion flow through the channel Normally inhibited by magnesium Permeable to Ca2+ Glycine acts as a co - agonist
32
Silent synapses
Synapses that only have NMDA receptors Can not function as requires depolarisation by AMPA receptors
33
Role of glutamate receptors
Learning and memory - activation of NMDA unregulates AMPA - strong, high frequency stimulation and Ca2+ entry causes long term potentiation
34
Stroke
- Ischaemia to part of the brain causing ischaemic necrosis and an infarct - release of K+ causes depolarisation in neighbouring neurones - increased glutamate release - increased Ca2+ influx - excitotoxicity
35
GABA and glycine receptors
Have integrated Cl- channels Opening the channels cause hyperpolarisation IPSP Decreased action potential firing
36
GABA GPCR
Modulators role
37
Barbiturates
Anxiolytics, antiepileptic and sedative actions Not used as sedative now due to risk of fatal overdose, dependence and tolerance Binds to GABA receptors and modulates the activity of GABA
38
Benzodiazepines
Binds to GABA receptors and modulates activity ``` Anxiolytic and sedative actions Treats: - insomnia - epilepsy - anxiety ```
39
Acetylcholine
Present in: - neuromuscular junctions - ganglion synapses in the ANS - postganglionic parasympathetic neurones Acts on: - nicotinic and muscarinic receptors in the brain Action: - mainly excitatory - can enhance the release of other transmitters,
40
Cholinergic pathways
Role: - arousal - learning - memory - motor control Location: - nucleus basalis - septal nuclei - hippocampus - thalamus - corpus striatum
41
Alzheimer’s disease
Involves degeneration of the cholinergic neurones in the nucleus basalis
42
Alleviation of Alzheimer’s disease symptoms
Cholinesterase inhibitors preventing the degradation of acetylcholine so more is available
43
Dopaminergic pathways
Mesocortical pathways and mesolimbic pathways: - mood - arousal - reward Nigrostriatal pathway - involves striatum and substantia nigra - motor control
44
Parkinson’s disease
Loss of dopaminergic neurones Loss of substantia nigra input to the corpus striatum Lack of dopamine release
45
Treatment of Parkinson’s disease
Levodopa - converted to dopamine by DOPA decarboxylase - precursor of dopamine - passes through the blood brain barrier via large neutral amino acid transporters LNAA - converted to dopamine in the brain via aromatic amino acid decarboxylase AADC - Carbidopa is also given to inhibit AADC in the periphery so extra dopamine is not produced in the periphery
46
Schizophrenia
Release of too much dopamine | - amphetamine releases dopamine and noradrenaline therefore can produce schizophrenic like behaviour
47
Anti psychotic drugs
Antagonists of the dopamine D2 receptor
48
Noradrenergic pathways
Cell bodies of noradrenergic neurones are found in the brain stem at the: - medulla - pons - locus ceruleus (majority) - diffuse release of noradrenaline throughout the cortex, hypothalamus, amygdala and cerebellum - from few neurones spreads widely
49
Activity of noradrenaline
- inactive during sleep - increased activity during behaviour arousal - amphetamines increases release of dopamine and noradrenaline to increase wakefulness
50
Depression
There is a relationship between mood and the state of arousal Depression may be associated with the lack of noradrenaline
51
Serotonergic pathways
Serotonin - similar distribution to neuroadrenaline Function: - sleep and wakefulness - mood
52
Serotonin selective reputable inhibitors
Treatment of depression and anxiety disorders
53
Norepinephrine
- Released by the locus coeruleus - released rostrally Role: - sleep - arousal Reticular formations project causally for muscle tone
54
Dopamine
Released by the substantia nigra and spreads via the nigrostriatal pathway Also released by the ventral tegmentum area Action: - mood - arousal - reward Viabthe mesolimbic and mesocortical pathways
55
Serotonin
Released by the raphe nuclei Projects rostrally Action: - sleep - mood
56
Acetylcholine
``` Released by the basal forebrain nuclei and the pontine nuclei Mostly excitatory Action: - arousal - memory - learning - motor control ```

Clinical neuroscience (20 decks)

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