Topic: inhibitory DREADDs

Among the genomic alterations identified as risk factors in Autism Spectrum Disorders (ASD), haploinsufficiency of AMBRA1 (Activating Molecule in Beclin1-Regulated Autophagy) triggers an ASD phenotype associated with hippocampal hyperexcitability exclusively in the female sex. Remarkably, AMBRA1 protein is constitutively more expressed in the hippocampus of wild-type (Wt) females than males. However, being more decreased by AMBRA1 deficiency in the female than the male sex, it results comparably expressed in the hippocampus of autistic females and non-autistic males. In this study, we verified

Dysfunction of GABAergic interneurons during sensitive time windows plays a crucial role in the etiopathogenesis of neurodevelopmental disorders. GABAergic transmission through Cl-permeable GABAA receptors (GABAAR) is depolarizing in pyramidal neurons of the CA1 region of the hippocampus of the Ts65Dn mouse model of Down syndrome. This depends on the upregulation of the Cl-importer NKCC1 and leads to an impairment of synaptic plasticity and memory in Ts65Dn adult mice. Accordingly, inhibiting NKCC1 rescues the Ts65Dn phenotype. However, the contribution of specific interneuron subpopulations t

Studies suggest that adaptive behaviors arise from multiple decision systems in the brain, and spatial complexity affects these processes. Three regions are hypothesized to make distinct contributions: hippocampus (HC) — encoding state-space and enabling flexible behaviors, dorsolateral striatum (DLS) — encoding action-chains and enabling automated behaviors, and prefrontal cortex (mPFC) — encoding task-space and strategy-setting. We simultaneously recorded across these regions, and in a separate cohort we chemogenetically inhibited mPFC on a rule-switch task, the left/right/alternation foragi