The impact of thalamic state on thalamocortical sensory processing

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Borden, Peter Young
Stanley, Garrett B.
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The sensory thalamus controls the transmission of information from the periphery to the cortex and shapes our sensory percepts. While the thalamus receives prominent afferent projections from the sensory periphery via the brainstem, thalamic activity is also shaped through diverse modulatory inputs that influence a range of thalamic state properties including the time-varying baseline thalamic polarization. Although many neurological disorders including schizophrenia, and central pain syndrome are linked to thalamic dysfunction, basic information about ongoing thalamic processing is still unknown. Specifically, it is unclear how ongoing changes in membrane polarization (i.e. state) alter the transmission of information to and from the cortex. The goal of this thesis was to develop novel techniques to measure entire cortical regions and to determine the role of thalamic state on tactile thalamocortical processing. In order to measure spatiotemporal cortical responses, we developed the techniques for recording the genetically expressed voltage indicators (GEVIs) for widefield imaging of the primary sensory cortex. We then utilized optogenetics to adjust the ongoing thalamic activity, and measured the sensory evoked cortical response using GEVIs in the vibrissa pathway of the anesthetized and awake mouse. We found that pre-stimulus modulations of thalamic polarization greatly impacted the thalamic spontaneous activity and evoked response to punctate sensory stimuli. In particular, we observed that pre-stimulus hyperpolarization controlled the level of thalamic bursting that occurred either spontaneously or was evoked by sensory inputs. Regardless of changes in the thalamus, we found that the overall neural state (anesthetized or awake) dictated the downstream cortical response to changes in thalamic polarization. These results highlight the dynamic nature of thalamocortical processing and suggest an important role of ongoing thalamic polarization for the encoding of sensory features. Taken even further, our work suggests that state-dependent processing may play a predominate role in neural circuitry that extends beyond even thalamocortical circuits. By better understanding how thalamic state controls function of the highly complex thalamocortical circuit, it will be possible to develop better treatment options for neurological disorders.
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