A detailed knowledge of the structure of the central nervous system is a prerequisite for studying its function, for understanding changes taking place during disease states, and for designing improved therapeutic strategies. Our studies focus on the molecular, cellular, and functional organization of the GABAergic system. As the main inhibitory neurotransmitter in the CNS, γ-aminobutyric acid plays an essential role in governing and coordinating the activity of neuronal networks and in regulating neuronal development.

A major feature of the GABAergic system is the heterogeneity of their constituents, notably postsynaptic receptors that are assembled from large subunit gene families. A precise knowledge of the cellular and subcellular localization of these proteins in adult and developing brain provides useful cues for designing studies of the functional organization of inhibitory neurotransmission.

Much of our current work is devoted to understanding the molecular organization of GABAergic synapses and on the mechanisms of GABAergic synaptic plasticity. To this end, we combine in vivo studies using mice with targeted mutations and in vitro work with primary neuronal cultures to determine how GABAergic synapses are assembled and contribute to various forms of neuronal signaling. In particular, we make use of adult neurogenesis as a model to investigate the role of GABAergic transmission in the regulation of neuronal proliferation, differentiation, and synaptic integration. Perturbing GABAergic signaling by targeted mutagenesis or over-expression/silencing of mutant synaptic proteins selectively in adult born neurons allows investigating their effects in a physiologically normal environment.

Animal models are essential tools for investigating cellular and molecular alterations that contribute to neurological and psychiatric disorders and to elucidate the role of abnormal GABAergic transmission in major brain diseases. To this end, we are working with mouse models of temporal lobe epilepsy and Alzheimer’s disease, with a specific focus on potential interactions between synaptic dysfunction in Alzheimer’s disease and epilepsy.  Further, we investigate the role of neuro-immune interactions and chronic inflammation in the pathophysiology of these disorders.