NIH Research Festival
The primary input area of the basal ganglia, the striatum, plays a role in integrating signals from the cortex, midbrain, and thalamus to make associations between stimuli, actions, and rewards. The canonical view was that midbrain activity drove all dopamine signals in the striatum. However, recent findings have forced the field to reconsider this viewpoint: cortical and thalamic inputs to the striatum can also produce local dopamine signals indirectly through striatal cholinergic interneurons. Here, we aimed to determine how cholinergic-evoked dopamine may be involved in visual learning. This would reveal a novel mechanism for learning specific associations and would be consistent with recent evidence linking corticostriatal circuits to visual learning. We used fiber photometry to measure striatal dopamine while animals learned a unilateral orientation-change detection task requiring them to report a visual stimulus change. While all mice had dopamine responses to the stimulus onset, only expertly performing mice developed a dopamine response to the stimulus change. We then used ex vivo voltammetry to measure evoked dopamine transients in trained animals. We found striking differences in the cholinergic-evoked component of the overall dopamine transient, dependent on visual task training. Interestingly, we found no primary sensory area connected strongly with cholinergic interneurons, leading to an inability to evoke dopamine signals. However, frontal cortical inputs are reliably connected directly to cholinergic interneurons, suggesting that these inputs could serve as potential mediators of dopamine signaling. These findings provide surprising information regarding corticostriatal connectivity and the neural circuits involved in visual learning and sensory perception.
Scientific Focus Area: Neuroscience
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