How are environmental cues routed to the brain?

We are interested in how environmental information that initiates adaptive changes in behavior reaches the brain. This includes chronic stress, lack of physical activity/sedentary lifestyle, and context dependent substance abuse (see right panel in Fig.above). Although initially adaptive, these environmental challenges eventually lead to long-term adverse, i.e. “maladaptive” responses, such as persistent generalized anxiety, antisocial behavior and drug seeking, topics extensively studied in our laboratory in various mouse models.

It is especially interesting when environmental cues are transmitted across generations, and therefore the individual receives environmental cues indirectly from its parents or grandparents (see left panel in Fig. above)). For example, a fetus or neonate, via the placenta or breast milk, can receive maternal signals related to the environment, which then initiate adaptive changes in the developing fetal/neonatal brain. Theoretical and empirical work suggests that once ancestral environment initiates adaptation during development, the individual is then “programmed” (i.e. its physiology and behavior are optimized) for life to that (matched) environment, and exhibits abnormal physiology/behavior in other, mismatched environments. Although this match/mismatch theory holds major significance in child/adolescent development and psychiatry, it is controversial because of a lack of experimental evidence and mechanistic understanding. Our laboratory has devised an experimental paradigm in which the difference between the maternal and offspring environments can be gradually changed and the resultant fitness level measured. This model provides us the opportunity to understand the mechanism underlying the match/mismatch paradigm