Thalamic reticular nucleus modulation of auditory thalamocortical function

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 DESCRIPTION (provided by applicant): The thalamic reticular nucleus (TRN) is a capsule of GABAergic neurons that partially envelops the thalamus and has been speculated to play a role in normal cognitive functions, such as selective attention, and in pathological states, such as tinnitus and schizophrenia. Therefore, understanding the function of the auditory portion of the TRN will unlock secrets not only about normal hearing, but also provide insights about how thalamocortical systems become dysfunctional in disease. Unfortunately, the impact of the TRN on sensory processing has been particularly inscrutable because of its small size and deep location. Until now, there has not been an experimental preparation that permitted measurement of thalamic and cortical activity at the cellular level while allowing simultaneous manipulation of the TRN and afferent input to the thalamus. We have recently overcome this hurdle by developing a brain slice preparation in the mouse that contains robust connectivity between the inferior colliculus, auditory thalamus, auditory TRN and the auditory cortex (Llano et al. J Neurophysiology 2014, 111(1):197). Herein, we combine the use of this new preparation with a range of optical, electrophysiological and pharmacological tools to test a novel hypothesis: that the TRN produces paradoxical rate- dependent enhancement of the transmission of neural signals as they pass through the colliculo-thalamocortical pathway. This hypothesis is based upon recent findings that the auditory TRN receives non-reciprocal input from wide-ranging neural structures, such as the frontal cortex and amygdala, and that GABAergic input from the TRN produces short windows of hyperexcitability in thalamic neurons by de-inactivating T-type calcium currents. Successful completion of this work will open the doors to future studies that examine the impact of the frontal cortex and amygdala on auditory thalamocortical systems through the TRN, and therefore will shed light on how cognitive and emotional states influence acoustic processing.