Deletion of NRXN1α impairs long-range and local connectivity in amygdala fear circuit.

Translational Psychiatry
Douglas AsedeMcLean M Bolton

Abstract

Neurexins are a family of presynaptic cell adhesion proteins that regulate synaptic structure and maintain normal synaptic transmission. Mutations in the α-isoform of neurexin1-gene (NRXN1α) are linked with cognitive and emotional dysregulation, which are heavily dependent on the amygdala and medial prefrontal cortex (mPFC). It is however not known whether deletion of NRXN1α gene affect specific synaptic elements within the amygdala microcircuit and connectivity with mPFC. In this study, we show that NRXN1α deletion impairs synaptic transmission between the dorsal medial prefrontal cortex (dmPFC) and basal amygdala (BA) principal neurons. Stimulation of dmPFC fibers resulted in reduced paired pulse ratio (PPR) and AMPA/NMDA ratio at dmPFC to BA synapses in NRXN1α-knockout (KO) (NRXN1α KO) mice suggestive of pre- and postsynaptic deficits but there was no change at the lateral amygdala (LA) to BA synapses following LA stimulation. However, feedforward inhibition from either pathway was significantly reduced, suggestive of input-independent deficit in GABAergic transmission within BA. We further analyzed BA inhibitory network and found reduced connectivity between BA GABAergic and glutamatergic neurons in NRXN1α KO mice. As this ...Continue Reading

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Citations

Feb 25, 2021·Cell Reports·M Felicia Davatolhagh, Marc V Fuccillo
Mar 24, 2021·Current Opinion in Genetics & Development·Marc V Fuccillo, ChangHui Pak
May 20, 2021·Cell Reports·Douglas AsedeM McLean Bolton

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Methods Mentioned

BETA
PCR

Software Mentioned

video Freeze , SOF -
VideoFreeze
Cite XLED1
Andor iQ
Graphpad Prism
NeuroMatic
Puncta analyzer
GraphPad
ImageJ
Clampex

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