Alex Dranovsky, MD, PhD

Virtually all mental and some medical illnesses are exacerbated by stress and alleviated by enriching experiences. Such experiences are thought to be causal or protective in cases of schizophrenia, anxiety/affective disorders, and substance abuse. Yet, the mechanisms by which experiences can confer or neutralize genetic risks for mental illness remain elusive. In a longstanding collaboration with David Leonardo, our lab is focused on deciphering how stressful and enriching experiences produce lasting changes in the postnatal brain, and how such changes can predict adaptive and maladaptive behaviors.

One major area of focus is the adult hippocampal stem cells. These stem cells are greatly affected by enriching and stressful experiences, producing more or fewer functional neurons. Thus, they are an ideal model system for studying the molecular, cellular, and circuit substrates for stressful and enriching experiences. Moreover, the hippocampal stem cell system provides a naturalistic setting for unraveling the molecular logic of neural stem cell renewal and differentiation. Through the use of inducible genetic manipulations in mice, in vitro cellular assays, transplantation studies, opto and chemogenetics, awake behaving in vivo recordings, and behavioral experiments we are exploring the mechanisms by which stressful and enriching experiences instruct stem cells to produce more stem cells or neurons in the adult hippocampus. Given the important role of the hippocampus as a modulator of the HPA axis, we are also examining the contribution of hippocampal stem cells and their progeny to how the animal adapts to stress.

Our second major focus is the mechanisms by which certain postnatal periods are particularly sensitive to the effects of stress and enrichment. Different experiences during such “critical” periods result in especially sustained behavioral phenotypes, but underlying changes in the brain are poorly understood. We are using computational approaches to analyze microscopic images and videos of mouse behavior to explore how the hippocampal stem cell system and other circuits across the whole brain can encode experiences during sensitive periods to establish sustained behavioral phenotypes.