Attentional deficits are a major cause of disability in individuals with autism. Recently, Vikaas Sohal and colleagues described a possible circuit mechanism contributing to attentional deficits in autism1. For the current project, Sohal proposes to identify a specific cellular locus underlying these circuit abnormalities.
Research has shown that attention normally increases the sensitivity of neural populations to incoming signals by decorrelating ongoing cortical circuit activity. Acetylcholine is hypothesized to mediate attentional decorrelations, likely by acting on vasoactive intestinal peptide (VIP)-expressing interneurons. Sohal’s recent study showed that cholinergic modulation can indeed decorrelate ongoing activity in prefrontal microcircuits1. Importantly, this ability is specifically lost in two etiologically distinct mouse models of autism: mice exposed to valproic acid and FMR1 knockout mice.
Sohal hypothesizes that VIP interneurons normally decorrelate cortical circuit activity, but that in autism, the ability of cholinergic modulation to recruit VIP interneurons is abnormal, causing deficits in cholinergic modulation-induced decorrelation and attention. Building on preliminary findings that VIP interneurons respond abnormally to cholinergic modulation in mouse models of autism and that VIP interneurons play critical roles in selective attention, the current project aims to test key aspects of this hypothesized pathophysiological mechanism.