Modular, Circuit-Based Interventions Rescue Hippocampal-Dependent Social and Spatial Memory in a 22q11.2 Deletion Syndrome Mouse Model.

Biological Psychiatry
Julia B KahnDouglas A Coulter

Abstract

22q11.2 deletion syndrome (22qDS) manifests with myriad symptoms, including multiple neuropsychiatric disorders. Complications associated with the polygenic haploinsufficiency make 22qDS symptoms particularly difficult to manage with traditional therapeutic approaches. However, the varying mechanistic consequences often culminate to generate inappropriate regulation of neuronal circuit activity. We explored whether managing this aberrant activity in adults could be a therapeutically beneficial strategy. To assess and dissect hippocampal circuit function, we performed functional imaging in acute slices and targeted eloquent circuits (specific subcircuits tied to specific behavioral tasks) to provide relevant behavioral outputs. For example, the ventral and dorsal CA1 regions critically support social and spatial discrimination, respectively. We focally introduced chemogenetic constructs in 34 control and 24 22qDS model mice via adeno-associated viral vectors, driven by excitatory neuron-specific promoter elements, to manipulate circuit recruitment in an on-demand fashion. 22qDS model mice exhibited CA1 excitatory ensemble hyperexcitability and concomitant behavioral deficits in both social and spatial memory. Remarkably, acute c...Continue Reading

Citations

Jan 10, 2021·Current Opinion in Neurobiology·Akiyuki WataraiTeruhiro Okuyama
Apr 21, 2021·Brain : a Journal of Neurology·Alexis M CrockettJorge I Alvarez

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22q11 Deletion Syndrome

22q11.2 deletion syndrome, also known as DiGeorge syndrome, is a congenital disorder caused by a partial deletion of chromosome 22. Symptoms include heart defects, poor immune system function, a cleft palate, complications related to low levels of calcium in the blood, and delayed development. Discover the latest research on this disease here.