Our lab investigates the underpinnings of cognitive optimization and decline in response to different environmental conditions. Physical exercise is known to improve performance on tasks that require the hippocampus, and we have also shown running-induced cognitive enhancement on tasks that require the medial prefrontal cortex (mPFC) in the rat. Similar to what has been observed for the hippocampus, running also increases dendritic spine density and synaptic protein expression in the mPFC, as well as the size of astrocytes and the expression of a water channel protein on their endfeet contacting blood vessels. These findings raise the possibility that running enhances cognition in part by stimulating plasticity among astrocytes. Using pharmacological and pharmacogenetic methods, we have shown that astrocyte signaling in the mPFC plays an important role in cognitive flexibility by influencing neuronal oscillations. Conversely, we have found that obesity impairs performance on mPFC- and hippocampus-dependent tasks and is associated with a reduction in dendritic spine density and changes in microglial reactivity. Ongoing studies in our lab are investigating the role of microglia in obesity-induced synapse loss and cognitive decline. Our recent work has investigated the effects of response learning on dendritic spine plasticity in the dorsal striatum. Response learning increases the number of dendritic spines on medium spiny neurons, raising the possibility that such changes are important for the acquisition and storage of habit memories.
Our lab explores mechanisms of avoidance behavior in rodents, which may reflect aspects of anxiety in humans. We study how these mechanisms are modified by experiences like physical exercise, obesity and early life adversity. Running is known to reduce avoidance behavior, as well as to enhance adult neurogenesis in the dentate gyrus and increase the number of dendritic spines throughout the hippocampal circuitry. Under conditions of stress, extracellular GABA is increased in the ventral hippocampus, a brain region implicated in anxiety regulation, and both new and mature excitatory neurons are silenced in the hippocampus of runners. Moreover, blockade of GABAergic receptors in the ventral hippocampus prevents running-induced avoidance behavior reduction. In other studies, we have shown that avoidance behavior under sedentary conditions involves neuronal gap junction signaling in the ventral hippocampal-medial prefrontal pathway. Gap junction protein expression is elevated in hippocampal interneurons of runners, but it remains unclear whether running-induced avoidance behavior reduction involves changes in gap junction signaling. Obesity and early life stress have both been shown to increase avoidance behavior, but the mechanisms of these effects remain unknown. Using a variety of behavioral, molecular and electrophysiological techniques, we are studying the role of new neurons, interneurons, perineuronal nets and microglia in modulating the neuronal circuitry underlying the regulation of avoidance behavior.
Our lab is interested in exploring the role of adult neurogenesis and other mechanisms of plasticity in mediating social behavior. We have found that living in a stable dominance hierarchy enhances adult neurogenesis in the hippocampus in rodent dominants compared to subordinates, an effect that is likely due to increased sexual behavior among dominants. Disruption of a stable hierarchy leads to increased aggression and an overall decrease in the production of new neurons regardless of dominance position. Reduced adult neurogenesis that occurs with social instability is associated with persistent changes in functions associated with the hippocampus, including anxiety regulation and social behavior. In a series of recent studies, we have found that social disruption-induced reduction in the number of new neurons plays an important role in shaping social behavior in a potentially adaptive way. Since one of the core deficits of autism spectrum disorder (ASD) is the presence of social impairments, we have also investigated hippocampal plasticity in multiple mouse models of social memory dysfunction. We found consistent reductions in the number of new neurons in the hippocampus of three such models, as well as changes in perineuronal nets in areas of the hippocampus that have been linked to social behavior and serve as targets for new neurons. Ongoing work in our lab involves investigating whether new neurons may serve as a potential therapeutic target for improving problematic behaviors in ASD.