“Hippocampal hyperactivity predicts psychosis and may disrupt aspects of cognition in schizophrenia. Here, …(Gilani and colleagues) use interneuron precursor transplants in mice lacking cyclin D2 (Ccnd2) to test links between hippocampal GABAergic interneurons and psychosis-relevant phenotypes. Ccnd2-null mice show parvalbumin interneuron deficits and increased in vivo hippocampal excitatory neuron spiking and metabolic activity. This hippocampal disinhibition is associated with cognitive deficits and excess dopamine activity. Transplanting interneuron progenitors derived from the embryonic medial ganglionic eminence into adult hippocampus mitigates these abnormalities. This study thus provides a paradigm for elucidating mechanisms by which limbic cortical interneuron hypofunction may contribute to cognitive deficits and dopamine dysregulation in psychosis. The sustained efficacy of the transplants supports a rationale for targeting hippocampal GABA interneurons with novel therapies for psychosis.”

Gilani AI, Chohan MO, Inan M, Schobel SA, Chaudhury NH, Paskewitz S, Chuhma N, Glickstein S, Merker RJ, Xu Q, Small SA, Anderson SA, Ross ME, Moore H: Interneuron precursor transplants in adult hippocampus reverse psychosis-relevant features in a mouse model of hippocampal disinhibition. Proc. Natl. Acad. Sci. USA [ Epub ahead of print, May 2, 2014


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