Dorsolateral Striatum is a Bottleneck for Responding to Task-Relevant Stimuli in a Learned Whisker Detection Task in Mice

Abstract

A learned sensory-motor behavior engages multiple brain regions, including the neocortex and the basal ganglia. How a target stimulus is detected by these regions and converted to a motor response remains poorly understood. Here, we performed electrophysiological recordings and pharmacological inactivations of whisker motor cortex and dorsolateral striatum to determine the representations within, and functions of, each region during performance in a selective whisker detection task in male and female mice. From the recording experiments, we observed robust, lateralized sensory responses in both structures. We also observed bilateral choice probability and pre-response activity in both structures, with these features emerging earlier in whisker motor cortex than dorsolateral striatum. These findings establish both whisker motor cortex and dorsolateral striatum as potential contributors to the sensory-to-motor (sensorimotor) transformation. We performed pharmacological inactivation studies to determine the necessity of these brain regions for this task. We found that suppressing the dorsolateral striatum severely disrupts responding to task-relevant stimuli, without disrupting the ability to respond, whereas suppressing whisker motor cortex resulted in more subtle changes in sensory detection and response criterion. Together these data support the dorsolateral striatum as an essential node in the sensorimotor transformation of this whisker detection task.Significance StatementSelecting an item in a grocery store, hailing a cab – these daily practices require us to transform sensory stimuli into motor responses. Many decades of previous research have studied goal-directed sensory-to-motor transformations within various brain structures, including the neocortex and the basal ganglia. Yet, our understanding of how these regions coordinate to perform sensory-to-motor transformations is limited because these brain structures are often studied by different researchers and through different behavioral tasks. Here, we record and perturb specific regions of the neocortex and the basal ganglia and compare their contributions during performance of a goal-directed somatosensory detection task. We find notable differences in the activities and functions of these regions, which suggests specific contributions to the sensory-to-motor transformation process.

Simultaneous single-cell calcium imaging of neuronal population activity and brain-wide BOLD fMRI

“…We show that different cortical and subcortical regions contain relevant predictive information about neural activity in the SSp-bfd. Interestingly, these regions are consistent with previous accounts of the mouse whisker system 22–25 , and the anatomical connections between these regions 29,31 .…”

“…We found that the neural population activity in the SSp-bfd could be predicted with a high accuracy from the BOLD fMRI activity in different regions of the mouse brain. This finding is consistent with previous studies in that regions implicated in whisker stimulation 22–25 , as well as anatomically connected areas 29,31 contained a high level of information about the local neural activity in the SSp-bfd. Using our method, future studies can now investigate whether regions across the brain contain distinct predictive information about diverse local neuronal subsets that differ in their genetics or projection specificity.…”

“…2a ; z-score ≥ 3.1, FWE P ≤ 0.00001, N = 6). Consistent with previous work, the main regions exhibiting BOLD signal increase included regions commonly involved in somatosensation such as the bilateral thalamus (TH), striatum (STR), secondary somatosensory area (SSs), orofacial domains (SSp-n) and the whisker domains (SSp-bfd) 22–25 . The strong activation of auditory regions, including the bilateral primary and dorsal auditory cortex (AUDp, AUDd) could be explained by the audible pneumonic pressure generated during stimulation.…”

Goal-Directed Learning is Multidimensional and Accompanied by Diverse and Widespread Changes in Neocortical Signaling

“…Experimental protocols have been approved by the IACUC of University of California, Riverside. The behavioral dataset used here includes studies that have been previously reported (Aruljothi et al, 2020; Marrero et al, 2022; Zareian et al, 2023; Zareian et al, 2021; Zhang & Zagha, 2023). Wild type (C57BL/6J, JAX #000664; BALB/cByJ, JAX #001026), transgenic (Snap25-2A-GCaMP6s-D, JAX #025111; Thy1-ChR2-YFP, JAX #007612; VGAT-ChR2-EYFP, JAX #014548), and virus-injected adult male and female mice were included in the behavioral learning data.…”

Role of Posterior Medial Thalamus in the Modulation of Striatal Circuitry and Choice Behavior

“…73,81,82,83,84,85,86 While some studies treat striatal inputs as a uniform entity, 87,88 they have been shown to differ anatomically, 73,74,76 functionally, 89,90 and behaviorally. 89,91,92 Thus, the specific cortical and thalamic origin of striatal inputs likely has significance for understanding how the striatal circuitry integrates sensorimotor information to modulate behavior.…”