Our lab is interested in fundamental questions in basic and translational neurobiology that ultimately may benefit patients with neuropsychiatric disorders. We are focused on the dentate gyrus region of the hippocampus, whose beautiful and well-understood cellular and circuit organization enables detailed structure-function studies. Important questions we are currently exploring include how environmental information, such as novelty, controls dentate memory functions. We also use genetic models of neurodevelopmental disorders to explore how developmental changes impact dentate structure and function. Finally, we are interested in pharmacological methods to intervene on dentate function in the context of neurodevelopmental abnormalities. We use several cutting-edge neuroscience techniques in rodent models along with behavioral tasks in our studies.
Mossy cells are a remarkably interesting glutamatergic neuron subtype located in the hilus of the dentate gyrus throughout the hippocampal dorsoventral axis. These neurons are more active than dentate gyrus granule cells and readily remap in different contexts. Mossy cells are important for the dentate's pattern separation role. We have previously shown that hyperactivation of ventral mossy cells impairs forms of dorsal hippocampal-dependent memory. Mossy cells also are highly sensitive to environmental novelty and stress. We are currently very interested in understanding how mossy cell circuits might integrate environmental information into memory processes.
We recently demonstrated that in mice most hippocampal glucagon-like peptide-1 receptor (GLP-1R) is expressed on mossy cells, especially ventral mossy cells, and that ventral mossy cells can be selectively activated by GLP-1R agonists given systemically. This is important because many GLP-1R agonists are already in clinical use to treat diabetes in humans, and as such could be readily repurposed. Current studies in the lab are focused on how GLP-1R agonists influence mossy cell function in cognition, as well as whether targeting this receptor during development in neuropsychiatric disease models can influence the integrity of the mossy cell system later in life.