Vaughn, M. J. | bioRxiv Science

bioRxiv2026

Synaptic GABA dysfunction of thalamocortical neurons impairs sleep spindle morphology and recovery from fearful memories.

The neural mechanisms which control the characteristic waxing and waning shape of sleep spindles and their dysregulation in neuropsychiatric illnesses are unresolved. Recent, sparse research shows post-traumatic stress disorder (PTSD) presents with abnormal spindle morphology and dysfunctional synaptic GABAA receptors in midline thalamic regions. We modeled this GABAA receptor dysfunction by localized CRISPR-Cas9-knockdown in mice. In contrast to a control group with intact GABAA receptors, mice with synaptic GABAA receptor knock-down in thalamocortical (TC) neurons lost the characteristic waxing and waning shape of sleep spindles and exhibited a failure to diminish conditioned contextual fear responses. Our results suggest that abnormally shaped sleep spindles may be a marker of synaptic GABA dysfunction in TC neurons and an indicator of disrupted fear extinction.

neuroscience↗

bioRxiv2025

Heterocellular and homocellular electrically coupled networks of the thalamus and cortex revealed by focal photomapping

Electrical synapses are expressed ubiquitously across the brain and are crucial components of active neural circuitry and connectomes. Identification of coupled networks in living tissue is limited by technical demands of multiplexed recordings, and no dyes, fluorescent reporters, or genetic labels can currently fill the gap. We introduce a novel method of identifying and quantifying electrical synapses, opto-{delta}L, that combines focal photostimulation of soma-targeted opsins with a spike timing-based computation for the strength of electrical synapses to rapidly measure and map electrically coupled networks in vitro. We leverage opto-{delta}L to show that coupled networks of the mature thalamic reticular nucleus extend as far as 100 m, synapse promiscuously across genetic subtypes of neurons, and couple 1-4 neighboring neurons to each recorded hub cell. We also demonstrate application of opto-{delta}L to cortical networks. These results highlight the broad potential of opto-{delta}L to interrogate the identity and roles of electrical synapses in circuitry, behavior, and cognition. TeaserElectrically coupled neural networks are newly unmasked by functional photomapping.

neuroscience↗