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Theme 1: Fundamental Neuroscience and the Brain > L7: Chemistry and Physiology of the Synapse > Flashcards

L7: Chemistry and Physiology of the Synapse Flashcards

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1
Q

What are the 3 types of ionotropic glutamate receptors?

A
  1. NMDA
  2. AMPA
  3. Kainate

They respond to glutamate as a ligand

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2
Q

Glutamate excitotoxicity

A

excessive Ca2+

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3
Q

Gs

A

stimulates adenylyl cyclase

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4
Q

Gi

A

inhibits adenylyl cyclase

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5
Q

Gq

A

stimulates phospholipase C

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6
Q

2 examples of receptors are Glutamate ionotropic receptors and GABA ionotropic receptors. Briefly describe their structure and action.

A
  • Receptors form an ion channel
  • contains central pore for ions to flow
  • contains a binding site for a ligand

Action:

  • Fast synaptic transmission
  • Binding of ligand causes conformational change in protein, which opens the channel
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7
Q

Glutamate ionotropic receptors

A
  • flux Na+
  • causes an EPSP (Excitatory Post Synaptic Potential)
  • depolarizing postsynaptic neuron.
  • fire an action potential.
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8
Q

GABA ionotropic receptors

A
  • flux Cl-
  • causes an IPSP (Inhibitory Post Synaptic Potential) -hyperpolarizing postsynaptic neuron
  • inhibits firing unless sufficient glutamate stimulation can counteract hyperpolarization.
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9
Q

Ionotropic receptors

-examples

A
  • Nicotinic
  • 5HT
  • ATP
  • Glycine
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10
Q

Synaptic integration

A

combination of all changes in membrane potential

considers both inhibitoty and excitatory inputs of cell and calculates overall potential

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11
Q

Metabotropic Receptors

  • structure
  • function
  • examples
A
  • Use a 2nd messenger
  • indirectly linked to ion channels
  • causes cascade of metabolic reactions intracellularly

Examples

  • GABA b
  • Metabotropic Glu
  • Beta adrenergic in the heart
  • DA

Slower than ionotropic

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12
Q

NMDA

  • Agonist
  • Antagonist
A

-Agonist
NMDA

-Antagonist
APV

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13
Q

AMPA

  • Agonist
  • Antagonist
A

-Agonist
AMPA

-Antagonist
CNQX

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14
Q

Kainate

  • Agonist
  • Antagonist
A

-Agonist
Kainic acid

-Antagonist
CNQX

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15
Q

Non-NMDA receptors

A

-AMPA and Kainate

  • Fast opening channels permeable to Na+ and K+
  • Responsible for early phase EPSP
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16
Q

NMDA receptor

A

Slow opening channel- late phase EPSP

-permeable to Ca2+ as well as Na+ and K+

  • requires glycine
  • neuroplasticity
  • long term memory formation?
17
Q

Mechanism of NMDA receptors

A
  • Non-selective ion channel
  • requires glycine as cofactor
  • Mg2+ blockade
  • membrane has to already be depolariced (in the presence of glutamate) to release Mg2+
  • flux of ions causes longer period of depolarisation.
  • Ca2+ lead to activation of enzyme=NEUROPLASTICITY
18
Q

phencyclidine (PCP, angel dust) and MK801

A

Inhibits NMDA receptor

this blockade of NMDA produces symptoms like hallucinations in Schizophrenia.

19
Q

NMDA receptors and excitotoxcity

A

Excessive Ca2+ influx
-activates enzymes that degrade proteins

can lead to stroke, cardiac arrest etc.

20
Q

Nicotine

Excitatory or modulatory?

A
  • excitatory at NMJ

- excitatory or modulatory in the CNS

21
Q

5HT

Excitatory or modulatory?

A

Excitatory or modulatory

22
Q

ATP

Excitatory or modulatory?

A

Excitatory

23
Q

How do antipsychotics work?

A

enhance flow through NMDA channel

24
Q

Autoreceptors

A

Modulation at the presynaptic level

regulates release of NT
“Give less”

25
Q

Heteroreceptors

A

modulation at the presynaptic level

regulates synthesis of NT
“Make less”

26
Q

How can you control transmission at the postsynaptic level?

A

Change transmission firing pattern
Directly at ligand gated ion channels or indirectly at GPCR
Neuroplasticity

27
Q

Enzyme linked receptors

-give example

A

Tyrosine kinase
Neutrotrophin binding (eg NGF)
Autophosphorylate on activation
downstream cascade

28
Q

3 properties of LTP

A

Temporal - summation of inputs leads to threshold

Associative- Simultaneous stimulation of strong and weak pathway = induce LTP in both pathways

Input Specific- LTP at one synapse not propagated to adjacent synapse

29
Q

AMPA

  • At resting potential
  • during depolarisation
A 
At RP: few AMPA
AMPA receptor is activated by Glutamate 
Allows influx of Na+ ions 
Influx of ions (EPSC) creates EPSP 
EPSP NOT sufficient to release of Mg2+ block or cause AP

Depolarisation:
more AMPA

30
Q

NMDA receptor

  • At resting potential
  • during depolarisation
A

At RP:
NMDA receptor IS NOT ACTIVATED as Mg2+ block
NO influx of Na+ AND Ca2+ ions
Result = Small EPSP = NO AP

Depolarization:

31
Q

What is the effect when Ca2+ goes through NMDA channel

A
  • Ca2+ activates NO synthase
  • activates guanlyl cyclase
  • produces 2nd messenger cGMP
  • leads to increased Glu release
32
Q

early phase LTP (acquisition)

A

When Glutamate binds NMDA on strongly depolarized post synaptic membrane (-40mV)
Ca2+ influx through NMDA receptors
Ca2+ binds to Calmodulin
Calmodulin activates CaMKII + PKC

Result = more AMPA + more efficient AMPAs = more EPSP = easier to induce AP

33
Q

Late phase LTP (consolidation)

A

-Need protein synthesis + gene transcription
-Insertion of AMPA receptors in early LTP at synapse INDEPENDENT of protein synthesis
Leads to phosphorylation of transcription factors such as CREB-1

34
Q

Long Term Depression (LTD)

A

Same players as LTP involved but slight differences:

  1. Still an NMDA-dependent process
  2. Triggered by lower levels of NMDA receptor activation = prolonged low level rises in Ca2+
  3. Ca2+ activated phosphatases rather than kinases
  4. Phosphatases lead to:
    - AMPA receptors being removed from membrane and being dephosphorylated

Theme 1: Fundamental Neuroscience and the Brain (24 decks)

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