Unbiased, High-Throughput Electron Microscopy Analysis of Experience-Dependent Synaptic Changes in the Neocortex

Area of Science:

• Neuroscience
• Synaptic Plasticity
• Cortical Circuitry

Background:

• Neocortical circuits undergo changes due to sensory and motor experiences, affecting synaptic properties.
• Previous research focused on specific neuronal pathways, leaving a gap in understanding column-wide adaptations.
• A comprehensive analysis is crucial for understanding how cortical circuits adapt to learning and altered sensory input.

Purpose of the Study:

• To perform an unbiased, broad-scale analysis of synaptic property changes across the entire cortical column.
• To investigate developmental and experience-dependent alterations in synaptic density and length.
• To identify new loci of synaptic plasticity in the neocortex.

Main Methods:

• Adaptation of electron microscopy for selective synapse labeling.
• Application of a machine-learning algorithm for semi-automated synapse detection.
• Comparative analysis of synapse density and length across development and during whisker-evoked plasticity in mice.

Main Results:

• Synapse density significantly increased in superficial layers (L1-L4) between postnatal days 14-18, with increased synapse length in L3 and L5B.
• Whisker deprivation for 24 hours led to increased synapse density in L2 and decreased density in L6, alongside increased length in L3.
• Electrophysiological analysis revealed a significant, nearly twofold increase in miniature excitatory postsynaptic current (mEPSC) frequency in L2 pyramidal neurons of the whisker-spared column.

Conclusions:

• Development and sensory experience dynamically alter neocortical synapse properties.
• The study utilized a semi-automated electron microscopy approach for unbiased, column-wide synaptic analysis.
• This method successfully identified novel sites of synaptic change, amenable to further electrophysiological verification and hypothesis generation.