Heather Cameron, PhD

Structural and Functional Roles for Adult Neurogenesis: Beyond Learning and Memory

Granule neurons continue to be generated in the mammalian dentate gyrus throughout life. These new neurons mature and integrate into hippocampal circuits, but the function of this ongoing neurogenesis is unclear. We are using pharmacogenetic mouse and rat models to specifically inhibit neurogenesis in order to study the structural and behavioral impact of chronic loss of adult neurogenesis in the dentate gyrus. Well-established hippocampal roles in learning and memory suggest that loss of new neurons should affect these functions. However, we find changes in many behavior tests that do not rely on learning and memory and instead suggest functions of the new neurons related to attention and motivation. We see that rats lacking adult neurogenesis focus more than controls on existing cues or tasks, paying less attention to distracting stimuli. In addition, new neurons increase the effort expended to gain small rewards with no effect on working for strong rewards. Effects are most prominent when there is a conflict between two opposing goals, such as seeking a reward or remaining in a safe location during a novelty-suppressed feeding task. These findings seem consistent with the idea that adult neurogenesis affects attention to lower salience stimuli or strategies.

Inhibiting neurogenesis also affects the structure of the hippocampus. In addition to causing the dentate gyrus to shrink, loss of adult neurogenesis prevents growth of pyramidal neurons and hippocampal volume during recovery from a single day of stress and during rewarded learning. In parallel with the lack of growth in these models, rats lacking new neurons fail to positively shift their anxiety-like and exploratory behaviors. These changes seen following positive and negative experiences suggest that adult-born neurons may act to set the tone, or bias, of behavioral choices in novel or ambiguous conditions.