Zahra Dhanerawala

Program: Neurosciences

Current advisor: Edward B. Han, PhD

Undergraduate university: Simmons College, 2018

Enrollment year: 2021

Research summary
Neuronal subtype control over hippocampal network function and goal-directed behavior

The hippocampus is a critical brain region for learning and memory. Hippocampal pyramidal neurons fire in specific places in the environment and this spatial map is thought to be the substrate on which new learning is built. Network inhibition plays a powerful role in controlling the plasticity that leads to learning, with each inhibitory neuron contacting thousands of excitatory neurons. Among the diversity of inhibitory neurons, vasoactive intestinal polypeptide (VIP)-expressing interneurons play an outsized role by selectively innervating other inhibitory interneurons; in effect, they regulate the regulators of plasticity. Numerous studies have found that the activity of VIP neurons controls cortical learning. In the hippocampus, silencing VIP neurons impairs goal-directed behavior, however the downstream circuit effects that enable this type of learning remain unknown. Using the critical importance of VIP neurons as a starting point, I am applying imaging approaches to perturb the activity of these neurons, while recording activity throughout the network to precisely define circuit alterations that support goal-directed learning.
My overarching hypothesis is that VIP activity supports goal-directed behavior via a somatostatin (SOM) interneuron to hippocampal pyramidal cell circuit involved in reward expectation. To study this neural circuit in dorsal CA1 of mouse hippocampus, I plan to use two-photon calcium imaging and closed-loop cell type-specific optogenetic perturbation in a hippocampal-dependent goal-directed VR task, in which mice receive water rewards for licking in a hidden reward zone and return to the same reward location in subsequent trials. Using this system, I will test whether manipulating the activity of VIP neurons during reward expectation affects goal-directed behavior and pyramidal cell activity and tuning. Additionally, I will investigate whether VIP neurons influence pyramidal cells indirectly via inhibition of SOM neurons, a class of inhibitory interneurons that control dendritic excitability and plasticity, by manipulating SOM neurons in the same task. The results of these experiments will further our understanding of the role of hippocampal VIP neurons in goal-directed behavior and provide a new avenue for therapeutics for mental health disorders and cognitive impairments.

Graduate publications