How does hippocampal hyperactivity influence hippocampal cognitive function?
A major goal of our lab's basic studies is to understand the circuit mechanisms underlying neuroimaging and other neurophysiological findings in patients. Several groups have reported that the anterior hippocampus in people with early psychosis or schizophrenia is hyperactive at baseline. We are interested in understanding how this baseline hyperactivity might influence and impair hippocampal-dependent cognitive processes. We are also interested in whether normalizing aberrant hyperactivity in circuits extending across the hippocampal longitudinal axis might improve learning and memory. To this end, we have focused on studying mossy cells of the ventral hippocampus. Mossy cells are a remarkably interesting glutamatergic neuron subtype located in the hilus of the dentate gyrus throughout the hippocampal dorsoventral axis. We have recently found that hyperactivation of ventral mossy cells impairs forms of dorsal hippocampal-dependent memory. Our future studies will explore how ventral mossy cell manipulations in disease models influence cognition.
How do nicotinic receptors influence social cognition?
The overall goal of our basic neurobiological research is to improve treatments for patients. Translational research therefore represents an important aspect of our research mission. Building upon our studies of aggressive behavior in mouse models, we will test whether nicotine, a drug that activates receptors called nicotinic acetylcholine receptors in the brain, improves the ability to make or withhold responses to faces that are either emotionally neutral or emotionally negative in a human clinical trial. This study will also test whether the drug affects brain activity while making or withholding responses using electroencephalography. Previous studies in people with schizophrenia have shown that more errors in response to negative emotional cues are related to greater likelihood of impulsive aggressive behavior. Therefore, the aim of this study is to determine whether nicotine might be a new strategy to reduce aggressive behavior. We would like to enroll about 30 participants with schizophrenia and 30 healthy controls in this study at Vanderbilt.