Lecture 11-Neuroscience Techniques Flashcards

1
Q

What role do MDGA proteins play in synaptic regulation?

A

MDGA proteins regulate the balance between excitatory and inhibitory synapses by interacting with Neuroligins (MDGA2 with Neuroligin-1 for excitatory synapses and MDGA1 with Neuroligin-2 for inhibitory synapses).

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2
Q

Where are excitatory and inhibitory synapses typically formed?

A

Excitatory synapses are primarily formed on dendritic spines, while inhibitory synapses form on dendrites or the cell soma.

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3
Q

What is the primary advantage of single-cell analyses in neurobiology?

A

Single-cell analyses allow precise genetic or pharmacological manipulation of neurons to study synapse formation and function.

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4
Q

What is a key limitation of single-cell analyses?

A

Single-cell analyses may not fully replicate how neurons behave in the intact central nervous system (CNS).

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5
Q

What is MDGA2? How does overexpression of MDGA2 affect synapse formation in cultured neurons?

A

-A protein that regulates the formation of synapses
- Overexpressing MDGA2 reduces the formation of both excitatory and inhibitory synapses.
- This is shown by fewer clusters of VGAT (inhibitory) and VGLUT1 (excitatory) markers.

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6
Q

What markers were used to study synapse formation in MDGA2 experiments?

A

VGAT was used to identify inhibitory synapses, and VGLUT1 was used to identify excitatory synapses.

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7
Q

What insights do neural circuit-level studies provide in neurobiology?

A

They offer a snapshot of synapse density and distribution, reflecting neural circuit organization during a specific developmental stage.

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8
Q

What is a two limitations of studying circuits?

A
  1. Minimal temporal resolution (samples show only a snapshot at one time, making it difficult to track changes or activity over time)
  2. Captures synaptic states at specific developmental stages, limiting dynamic understanding of synaptic changes.
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9
Q

What is a key limitation of studying neuronal function in brain slices?

A
  • Neuronal function studies often use isolated brain tissue or cells, not the whole brain.
  • Results may reflect changes caused by the experiment setup, not normal brain activity.
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10
Q

How does the level of resolution in neuronal function assessments help study synaptic activity?

A

It allows direct assessment of changes in cellular characteristics and synaptic inputs, ranging from single channel to whole cell analysis.

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11
Q

What are two caveats studying neuronal networks?

A
  • It’s difficult to distinguish between network effects and those from individual cells
  • Only measuring some parts of the network can miss important interactions and affect understanding of the whole network’s function.
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12
Q

What does the “Neuronal Networks” resolution level focus on and what scales does it assess?

A
  • It focuses on population responses to understand how groups of neurons behave and how network properties change, from a single neuron to multiple neurons within a network.
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13
Q

What is a caveat when studying synaptic plasticity in relation to brain disorders?

A

Synaptic plasticity changes can occur without behavioral signs of neuropathologies, making it hard to directly link them to observable symptoms.

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14
Q

What does the “Neural Plasticity” resolution level assess and how is altered synaptic plasticity linked to brain disorders?

A
  • It assesses how neural networks respond to changes in neural activity related to cognition.
    -Altered synaptic plasticity may be an early sign of brain disorders.
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15
Q

What is a caveat when using animal models (e.g., mice) to study neurological disorders?

A

Mice are not humans, so the results may not directly apply to humans, and there could be other reasons for the observed traits.

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16
Q

What happens to excitatory synapse numbers following reduction of MDGA2?

A
  • Reduction of MDGA2 increases excitatory synapse numbers in vivo.
  • This increase is observed in both Pyramidal and Radial cell areas.
17
Q

What synaptic proteins are upregulated in the hippocampus of Mdga2+/- mice?

A
  • MAGUK, NL1, and VGlut1 are upregulated in the hippocampus of Mdga2+/- mice.
  • The upregulation is most significant for MAGUK and NL1 (Neuroligin 1).
18
Q

What does the upregulation of MAGUK and NL1 suggest about synaptic function in Mdga2+/- mice?

A

The upregulation of MAGUK and NL1 suggests an increase in synaptic strength and possibly synaptic plasticity in response to reduced MDGA2.

19
Q

What role do AMPA and NMDA receptors play in excitatory synaptic transmission?

A
  1. AMPA receptors (AMPAR) mediate basal synaptic transmission (normal signalling) and increase with synaptic activity.
  2. NMDA receptors (NMDAR) induce synaptic strength changes during activity.
20
Q

How does the reduction of MDGA2 affect AMPA receptor expression in synapses?

A
  • Leads to an increase in the surface expression of AMPA receptors (GluA1) in synapses.
  • Suggests enhanced synaptic transmission and possible changes in synaptic plasticity.
21
Q

How does the reduction of MDGA2 affect synapse number and strength, and what does an increase in mEPSC frequency and amplitude indicate?

A
  • Reduction of MDGA2 increases synapse numbers and strength, raising mEPSC frequency (more synaptic events) and amplitude (stronger synaptic responses and greater synaptic strength).
22
Q

What is the effect of MDGA1 reduction on inhibitory synapse density in mice?

A
  • Show increased inhibitory synapse density in both Pyramidal and Radial layers.
  • This suggests that MDGA1 regulates synapse density, particularly inhibitory synapses.