Grant: CIHR New Investigator

The discovery that neurons are added to the adult brain of nearly all mammals examined, including humans, has profoundly changed our understanding of the potential for plasticity in the brain. One region of the adult brain that has high levels of adult neurogenesis is the hippocampus, a structure critically involved in learning and memory. In the hippocampus, new neurons are better at forming connections and are more active than pre-existing neurons, suggesting that they may preferentially contribute to memory processes. Consistent with this possibility, animals that lack adult neurogenesis show a variety of memory-related impairments. However, the hippocampus also regulates and is highly sensitive to stress. Stress prevents the addition of new neurons and drugs and experiences that protect against stress, such as antidepressants, environmental enrichment and exercise increase the addition of new neurons. Furthermore, animals lacking neurogenesis are more vulnerable to the negative behavioural and hormonal effects of stress. Since memory is also heavily regulated by stress it is likely that stress impacts memory through its effects on neurogenesis, although this has never been explored. This proposal will therefore examine the effects of stress on learning-related properties of new neurons. First, we will examine whether stress alters the ability of new neurons to form connections in the brain, which is thought to be an essential biological component of memory. Second, we will identify whether a dysfunctional response to stress underlies the memory impairments seen in animals that lack neurogenesis. Given the contribution of stress to a broad array of mental health disorders it is expected that these results will directly contribute to novel treatments for people suffering from memory and mood disorders.