Grant: CIHR Fellowship

Adolescence is a dynamic period characterized by maturation of higher-order cognitive functions, including decision-making and working memory, to their adult levels. It can also be a period of increased risk-taking, during which some individuals commence use of drugs such as cannabis. Several of the biological changes that support adolescent maturation of complex behavior occur within a brain region called the prefrontal cortex (PFC). Given the extended development of PFC, it is particularly vulnerable to the deleterious effects of drug-taking during adolescence, which may have lasting consequences on cognition and increase risk for psychiatric disorders including schizophrenia. Indeed, past research has shown that cannabis exposure, particularly during the early adolescent period, leads to enduring changes in cognitive and emotional processes that stem from PFC functional changes. In particular, certain PFC cells that release the inhibitory neurochemical GABA undergo physiological maturation during adolescence that is disrupted by drug exposure. PFC GABA cells are also impacted in schizophrenia, and may represent the cellular mechanism by which cannabis exposure increases the risk of developing the disorder. This proposal is aimed at identifying the cellular players that underlie the long-lasting effects of cannabis use during adolescence within PFC. It uses electrophysiological approaches to examine how cannabis exposure affects the function of particular types of PFC GABA cells, including how they process input from other brain regions, coupled with behavioral approaches probing how these alterations may be implicated in cognitive changes relevant to psychiatric disorders. These insights into impacts of cannabis may be particularly valuable given its recent legalization and possible increased accessibility for adolescents. Furthermore, the work has the potential to identify new intervention targets for schizophrenia and other psychiatric disorders.