Lecture 11-Neuroscience Techniques Flashcards
What role do MDGA proteins play in synaptic regulation?
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).
Where are excitatory and inhibitory synapses typically formed?
Excitatory synapses are primarily formed on dendritic spines, while inhibitory synapses form on dendrites or the cell soma.
What is the primary advantage of single-cell analyses in neurobiology?
Single-cell analyses allow precise genetic or pharmacological manipulation of neurons to study synapse formation and function.
What is a key limitation of single-cell analyses?
Single-cell analyses may not fully replicate how neurons behave in the intact central nervous system (CNS).
What is MDGA2? How does overexpression of MDGA2 affect synapse formation in cultured neurons?
-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.
What markers were used to study synapse formation in MDGA2 experiments?
VGAT was used to identify inhibitory synapses, and VGLUT1 was used to identify excitatory synapses.
What insights do neural circuit-level studies provide in neurobiology?
They offer a snapshot of synapse density and distribution, reflecting neural circuit organization during a specific developmental stage.
What is a two limitations of studying circuits?
- Minimal temporal resolution (samples show only a snapshot at one time, making it difficult to track changes or activity over time)
- Captures synaptic states at specific developmental stages, limiting dynamic understanding of synaptic changes.
What is a key limitation of studying neuronal function in brain slices?
- 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.
How does the level of resolution in neuronal function assessments help study synaptic activity?
It allows direct assessment of changes in cellular characteristics and synaptic inputs, ranging from single channel to whole cell analysis.
What are two caveats studying neuronal networks?
- 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.
What does the “Neuronal Networks” resolution level focus on and what scales does it assess?
- 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.
What is a caveat when studying synaptic plasticity in relation to brain disorders?
Synaptic plasticity changes can occur without behavioral signs of neuropathologies, making it hard to directly link them to observable symptoms.
What does the “Neural Plasticity” resolution level assess and how is altered synaptic plasticity linked to brain disorders?
- 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.
What is a caveat when using animal models (e.g., mice) to study neurological disorders?
Mice are not humans, so the results may not directly apply to humans, and there could be other reasons for the observed traits.
What happens to excitatory synapse numbers following reduction of MDGA2?
- Reduction of MDGA2 increases excitatory synapse numbers in vivo.
- This increase is observed in both Pyramidal and Radial cell areas.
What synaptic proteins are upregulated in the hippocampus of Mdga2+/- mice?
- MAGUK, NL1, and VGlut1 are upregulated in the hippocampus of Mdga2+/- mice.
- The upregulation is most significant for MAGUK and NL1 (Neuroligin 1).
What does the upregulation of MAGUK and NL1 suggest about synaptic function in Mdga2+/- mice?
The upregulation of MAGUK and NL1 suggests an increase in synaptic strength and possibly synaptic plasticity in response to reduced MDGA2.
What role do AMPA and NMDA receptors play in excitatory synaptic transmission?
- AMPA receptors (AMPAR) mediate basal synaptic transmission (normal signalling) and increase with synaptic activity.
- NMDA receptors (NMDAR) induce synaptic strength changes during activity.
How does the reduction of MDGA2 affect AMPA receptor expression in synapses?
- Leads to an increase in the surface expression of AMPA receptors (GluA1) in synapses.
- Suggests enhanced synaptic transmission and possible changes in synaptic plasticity.
How does the reduction of MDGA2 affect synapse number and strength, and what does an increase in mEPSC frequency and amplitude indicate?
- Reduction of MDGA2 increases synapse numbers and strength, raising mEPSC frequency (more synaptic events) and amplitude (stronger synaptic responses and greater synaptic strength).
What is the effect of MDGA1 reduction on inhibitory synapse density in mice?
- Show increased inhibitory synapse density in both Pyramidal and Radial layers.
- This suggests that MDGA1 regulates synapse density, particularly inhibitory synapses.
