Thalamocortical state control of tactile sensing: Mechanisms, Models, and Behavior Despite the fact that the sensory thalamus plays a major role in shaping sensory representations in cortex, and thus shaping our percepts, most of what we know has been determined through electrophysiological investigation of the thalamus in-vitro or in the anesthetized brain. Properties of thalamic activity such as mean firing rates, timing and synchrony, and tonic/burst firing directly determine how sensory inputs are represented in the spatiotemporal activation of cortex. Modulations in thalamic ?state? through changes in baseline levels of depolarization strongly influence the gating properties of the dynamic relay of sensory signals to cortex during normal behavior. Using the vibrissa pathway of the awake mouse, our team is uniquely positioned to precisely quantify and control thalamic state, and measure the downstream impact on spatiotemporal cortical representations, using a range of multi-scale electrophysiological and optical measurements, causal manipulations, modeling, and sensory behavioral tasks. We will first Determine Thalamic State Control of Sensory Information Processing in the awake mouse (Aim 1). A range of separate experiments will utilize single unit and LFP recording across thalamus and S1 and widefield genetically expressed voltage sensor imaging in S1 to fully capture and model the range of modulations in thalamic firing, synchronization, and tonic/burst firing in the awake brain. We will then conduct experiments that parallel Aim 1 in which we optogenetically manipulate thalamic state, to determine the causal role of thalamic firing modes on spatiotemporal representations of sensory inputs in cortex (Aim 2). Finally, we will Determine Thalamic State Control of Sensory Percepts in behavior, in a well-defined whisker detection and spatial (two-whisker) discrimination tasks (Aim 3), employing the same electrophysiology/imaging and optogenetic manipulation approaches across thalamus and cortex as in Aims 1 and 2. Significance: The thalamocortical circuit is continuously controlled by modulatory inputs that fundamentally shape information processing relevant for perception and behavior. However, the precise link between thalamic state and the resultant percept remains a major open question in neuroscience. We will determine how cortical representations changes through modulation in thalamic input and the consequences of this on perception. Broad Impacts: Dysfunction of brain state has been implicated in an incredibly wide range of neurological disorders ranging from dysfunction of arousal in narcolepsy to dysfunction of neuromodulators in mood disorders such as depression. Furthermore, recent genome wide association studies have implicated voltage-gated calcium channels found in brain structures including thalamus and cortex as risk loci for both schizophrenia and bipolar disorder. Finally, we also assert that understanding of the interaction between brain state and sensory representations is requisite for delivery of surrogate inputs in prostheses.

Public Health Relevance

Sensory input is critical in our daily lives, for both the perception of the world around us, and in providing feedback for our muscle systems that help us interact with the external world. How the nervous system performs this feat, and precisely how this helps us in our environment, is unknown. Discovery in this area can potentially help us understand a number of disorders/diseases of the nervous system for which individuals exhibit loss of sensitivity, and do not have the ability to adapt to changes in the sensory environment.

National Institute of Health (NIH)
National Institute of Neurological Disorders and Stroke (NINDS)
Research Project (R01)
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Special Emphasis Panel (ZRG1)
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David, Karen Kate
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Georgia Institute of Technology
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Biomed Engr/Col Engr/Engr Sta
United States
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Waiblinger, Christian; Wu, Caroline M; Bolus, Michael F et al. (2018) Stimulus context and reward contingency induce behavioral adaptation in a rodent tactile detection task. J Neurosci :