Integration of the thalamic and cortical inputs in the auditory striatum

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Animals facing a decision routinely use sensory including auditory information from the outside world to guide optimal behavior. For example, we listen for instructions from the GPS when trying to take the best route to a destination. The dorsal striatum is a critical brain region in this sensory-guided decision-making process. The long-term goal of my laboratory is to understand the circuitry and mechanisms through which the dorsal striatum transforms auditory stimuli into appropriate actions. Anatomical studies have shown that individual neurons in the dorsal striatum receive convergent inputs from both the thalamus and the cortex. Previous studies in associative striatum (rostral dorsal striatum) suggest that these two input pathways play distinct roles in behaviors. Our studies in sensory striatum (caudal dorsal striatum) indicate that projections from both the auditory thalamus and the auditory cortex are required for decision-making in rodents performing an auditory frequency-discrimination task. The primary objective of this proposal is to determine how the auditory striatum integrates these thalamic and cortical inputs, and how this integration contributes to auditory frequency-discrimination decision-making and learning. The studies proposed address the fundamental hypothesis that both thalamic and cortical inputs contribute to auditory decision- making by differentially modulating striatal sound representations, and by shaping striatal synaptic plasticity during task learning. In Aim 1, we will determine how striatal sound representation is regulated by the thalamic and cortical inputs. We will use in vivo tetrode recording on awake mice to examine the responses of striatal neurons to pure tones while thalamic or cortical inputs are selectively silenced during stimulus presentation. In Aim 2, we will examine how striatal neurons integrate the thalamic and cortical inputs using whole-cell patch recording in brain slice combined with opto-genetic and pharmacological applications. In Aim 3, we will examine the development of thalamostriatal plasticity during task learning and test how thalamic input influences the learning-induced corticostriatal plasticity, using in vivo tetrode recording on behaving mice. The proposed experiments will determine how thalamostriatal and corticostriatal pathways regulate auditory striatal activity and plasticity, the physiological mechanisms underlying their functions in auditory decision-making. We focus on the auditory striatum in this study, but the findings may be generalized to the whole sensory striatum. These results will also contribute to the understanding of brain disorders like Parkinson’s and Huntington’s disease that involve differential changes of activity and plasticity at thalamostriatal and corticostriatal synapses.