Adult neurogenesis and the dentate gyrus

Our research focuses on understanding the functional characteristics of neurons in the dentate gyrus. We use electrophysiological, imaging, and molecular biological techniques to study the activity of dentate neurons throughout their course of maturation, as well as the surrounding inhibitory and excitatory neurons with which they interact. Our goal is to gain insight into synaptic and network mechanisms that underlie the function of this intriguing brain region.
Our lab is currently addressing the following questions:

1) What properties do newborn neurons provide to the network?

Adult neurogenesis encompasses the progression of newly generated cells through sequential developmental stages that include neuronal differentiation and synaptic integration into the mature neural network (see cartoon). We are studying the functional properties of granule cells throughout their development, as well as their interactions with other local neurons, to understand how adult generated neurons contribute to the overall function of the dentate gyrus
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Progression of granule cell maturation. From Zhao and Overstreet-Wadiche, 2008.

2) What controls the survival of newborn neurons?

Many newborn neurons are generated but the proportion that attains stable integration into the circuit is limited by the considerable cell death that occurs during a critical period in their maturation. Survival of newborn neurons in this critical period is regulated independently of neural production/proliferation, and ultimately determines the number of new neurons added to the circuit. We are studying how the earliest synaptic inputs to newborn neurons control their long-term survival.


3) How does neurogenesis contribute to pathological alterations in DG function?

Physiological stimuli such as exercise and environmental enrichment enhance adult neurogenesis and improve cognitive function. Pathological stimuli including seizures and traumatic brain injury can even more dramatically alter neurogenesis, not only affecting the number of cells but also resulting in abnormal functional integration. We are testing how brain insults including seizures and traumatic brain injury alter the function of dentate granule cells.