Sebnem Nur Tuncdemir

My lab is interested in understanding how the neural circuits that encode specific features of contexts are organized in adults and the key developmental mechanisms by which this network is formed. We study the hippocampal circuitry underlying flexible memory encoding using imaging and neural manipulation methods in awake behaving mice. We also aim to understand the neural mechanisms of the impairments in cognitive flexibility, a common endophenotype of many psychiatric disorders. Ultimately, an integrated view of a circuit function from the activity of its component cell types at multiple time scales, across the lifespan will provide new biomarkers for disorders characterized by impaired cognitive discrimination such as post-traumatic stress disorder (PTSD) and anxiety disorders. Currently the work in the lab focuses on two main questions: 1- How does neural diversity in the hippocampus contribute to memory? The hippocampal dentate gyrus is densely packed with sparsely active excitatory granule cells and previous work used to think about this circuit having only a single type of sparsely active place cells which encode the animal’s position within an environmental context by integrating across all the sensory information relevant to estimating its location. But by chronically imaging a large population of granule cells using two-photon calcium imaging we have found an additional population encoding sensory cues. We will now figure out how different these cells are and why they are different, by measuring and manipulating the activity of afferent to the dentate gyrus. Using a combination of in vivo imaging, transgenic tagging and manipulation strategies as well as computational analysis of somatic and projection neural activity we will investigate the mechanisms by which multisensory information arriving from the external world generates the functional diversity in the dentate representations. 2- What is the developmental basis to the brain’s response to stress and antidepressants? Numerous studies have shown that the developmental time course of the formation of the hippocampal principal neurons matches their anatomical location and determines their wiring into the hippocampal circuits. Yet, how this developmental sequence affects the function of the neurons during cognitive behaviors remains unclear. In previous work, we have shown that adult born immature granule cells bidirectionally modulate diverse responses in the dentate gyrus; they increase remapping of place cells while decreasing remapping of cue cells. We will now ask whether such age-dependent specialization of function also applies to developmental neurogenesis or if the functional diversity emerges through experience after integration into the dentate network. We will also address clinically relevant questions of how do developmentally differentiated functional groups of dentate gyrus neurons respond to stress and antidepressant treatment and how their activity can be harnessed to develop novel circuit-based treatments of stress-induced psychopathologies, such as PTSD and depression.

[2023] Adult-born granule cells facilitate remapping of spatial and non-spatial representations in the dentate gyrus. Tuncdemir, Sebnem N; Grosmark, Andres D; Chung, Hannah; Luna, Victor M; Lacefield, Clay O; Losonczy, Attila; Hen, Rene. Neuron 2023 Oct;