A human-specific modifier of cortical connectivity and circuit function

Schmidt ERE
Columbia University
October 22, 2021
Nature
https://pubmed.ncbi.nlm.nih.gov/34707291

This article is currently being updated. View its version on PubMed.

https://pubmed.ncbi.nlm.nih.gov/34707291

Research summary

Expression of the human‑specific paralog SRGAP2C in mice increases local and long‑range cortico‑cortical connectivity, enhances sensory coding in layer 2/3 pyramidal neurons, and improves performance in a cortex-dependent sensory discrimination task. Computational modeling linked increased Layer 4→Layer 2/3 connectivity with behavioral improvements

Key outcome of the study

Cortical connectome remodeling: increased excitatory/inhibitory synapses on L2/3 PNs; enhanced activation fraction under sensory stimulation; improved cortex-dependent learning/memory

Model

SRGAP2C humanized Knockin mouse: CAG-floxed STOP-3×HA-SRGAP2C inserted into Rosa26 locus, inducible in cortical pyramidal neurons — genOway‑developed, C57BL/6 background

TARGET:
Srgap2c
Synonyms:

Keywords

Human evolution; cortical circuit modeling; synaptic density; sensory discrimination tasks; neurodevelopment; human-specific gene function

Technical specifications

Rosa26-targeted human SRGAP2C transgene Knockin; floxed-STOP CAG promoter; Cre-inducible targeting in all cortical pyramidal neurons; rabies-based circuit tracing; in vivo two-photon Ca²⁺ imaging; behavioral sensory discrimination assays

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