Distinct in vivo dynamics of excitatory synapses onto cortical pyramidal neurons and inhibitory interneurons

Cell Reports. 2021 Apr 5; doi: https://doi.org/10.1101/2020.12.03.409417

Joshua B. Melander, Aran Nayebi, Bart C Jongbloets, Dale A. Fortin, Maozhen Qin, Surya Ganguli, Tianyi Mao, Haining Zhong

Abstract
Cortical function relies on the balanced activation of excitatory and inhibitory neurons. However, little is known about the organization and dynamics of shaft excitatory synapses onto cortical inhibitory interneurons, which cannot be easily identified morphologically. Here, we fluorescently visualize the excitatory postsynaptic marker PSD-95 at endogenous levels as a proxy for excitatory synapses onto layer 2/3 pyramidal neurons and parvalbumin-positive (PV+) inhibitory interneurons in the mouse barrel cortex. Longitudinal in vivo imaging reveals that, while synaptic weights in both neuronal types are log-normally distributed, synapses onto PV+ neurons are less heterogeneous and more stable. Markov-model analyses suggest that the synaptic weight distribution is set intrinsically by ongoing cell type-specific dynamics, and substantial changes are due to accumulated gradual changes. Synaptic weight dynamics are multiplicative, i.e., changes scale with weights, though PV+ synapses also exhibit an additive component. These results reveal that cell type-specific processes govern cortical synaptic strengths and dynamics.

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Genetically encoded sensors towards imaging cAMP and PKA activity in vivo

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High-fidelity, efficient, and reversible labeling of endogenous proteins using CRISPR-based designer exon insertion