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Quantitative Fluorescence Analysis Reveals Dendrite-Specific Thalamocortical Plasticity in L5 Pyramidal Neurons

Ajit Ray1, Joseph A Christian1, Matthew B Mosso1

  • 1Department of Biological Sciences, Carnegie Mellon University, Pittsburgh Pennsylvania 15213.

The Journal of Neuroscience : the Official Journal of the Society for Neuroscience
|January 14, 2023
PubMed
Summary

Synaptic changes in the mouse barrel cortex during whisker learning are transient and compartment-specific. Fluorescence microscopy reveals rapid, temporary alterations in thalamocortical synapses during early sensory association training.

Keywords:
LTPPOm thalamusapical dendriteintrabodieslearningplasticity

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Area of Science:

  • Neuroscience
  • Cellular Biology
  • Learning and Memory

Background:

  • Synaptic plasticity is fundamental to learning, experience, and neurological conditions.
  • Assessing synaptic plasticity requires neuroanatomical methods that provide spatial information for modeling neuronal computations.
  • Existing methods are often technically and financially demanding.

Purpose of the Study:

  • To monitor changes in thalamocortical synapses onto different compartments of layer 5 (L5) pyramidal neurons during whisker-dependent learning.
  • To develop and validate a fluorescence-based analytical method for studying synapse-specific plasticity.
  • To investigate the transient nature of synaptic changes in primary sensory cortices during learning.

Main Methods:

  • Utilized fluorescence-based reagents for presynaptic and postsynaptic labeling in fixed tissue from Rbp4-Cre transgenic mice.
  • Employed axonal fills and molecular-genetic tags for synapse identification.
  • Corroborated anatomical measurements with electrophysiological recordings at various training stages.

Main Results:

  • Thalamocortical synapses from the posterior medial thalamic nucleus exhibited rapid, transient morphologic changes in both presynaptic and postsynaptic structures.
  • Synaptic size increases were compartment-specific, occurring selectively in proximal dendrites of L5 pyramidal neurons, not apical tufts.
  • These structural changes normalized as animals achieved expertise in the task.

Conclusions:

  • Fluorescence-based analysis provides an efficient method to study input, cell type, and dendritic location-specific synaptic plasticity.
  • The developed method confirms prior electrophysiological findings and predicts functional synapse strength in a pathway-specific manner.
  • Synaptic alterations in primary sensory cortices are transient, primarily occurring during the early stages of learning.