Functional interrogation of the mouse somatosensory thalamic interneuron in sensory perception and rhythmic states

ABSTRACT/SUMMARY The mouse somatosensory thalamus participates in fundamental processes including sensory processing, sleep and pathological rhythmic behaviors like seizure. Local thalamic interneurons have been considerably overlooked due to their sparsity in the total neuronal population. However, their extensive dendritic arborizations spanning almost the entire breadth of the nucleus, together with my preliminary data, point to an important role for these cells in thalamic functions. Thalamic interneuron dendrites are capable of releasing synaptic vesicles, defying traditional definitions of neuronal input and output structures, while greatly increasing their capacity for complex computations. Of interest, local thalamic interneurons are also capable of forming diverse and uncommon synaptic relationships including triadic synapses. The primary conceptual goals this project seeks to address are to define the rules that govern dendritic signal integration and to define the functional role these interneurons play in the canonical thalamocortical circuit. I hypothesize that unique structural features enable unique functions. Specifically, I predict that electrotonically isolated dendritic locations enable numerous encoding processes to occur simultaneously and independently from the soma. Thus, thalamic interneurons pose unique opportunities to study fundamental principles of neuronal computation including the ambiguous role of triadic inhibition. Taking place at Columbia University with Sponsor Prof. Chris Makinson and Co-Sponsor Prof. Liam Paninksi, I will use the newest generation of high-gain voltage indicators and multi-photon in vitro and in vivo imaging to investigate the imperative questions outlined above. This fellowship represents a substantial opportunity for high-quality training in state-of-the-art imaging and computational neuroscience techniques and approaches that complement my background in neurobiology and electrophysiology. I aim to address the influence of local interneurons in thalamic functions by observing and manipulating their activity during thalamic oscillations. I will also apply synthetic synaptic inputs to probe with precision input distribution patterns and the biophysical mechanisms underlying dendritic integration in thalamic interneurons. Data from these experiments will be used to build realistic and well constrained computer simulations to further test precise mechanisms in shaping receptive field structures. I expect to find that interneurons act as an integral member of the thalamocortical circuit and to gain insight into fundamental concepts of neuronal computation through their interrogation. Moving forward, I hope to build upon the conceptual and technical advances outlined here to uncover the causative mechanisms involved in sensory perception and the role of thalamic interneurons in disease.