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.

A learned sensory-motor behavior engages multiple brain regions, including the neocortex and the basal ganglia. How these brain regions coordinate to affect sensory selection (for target stimuli) and inhibition (for distractor stimuli) remains unknown. Here, we performed laminar electrophysiological recordings and muscimol inactivation in frontal cortex and dorsolateral striatum to determine the representations within and functions of each region during selective detection performance. From the recording experiments, in deep layers of frontal cortex and dorsolateral striatum we observed similar encoding of sensory and motor features. However, muscimol inactivation of each region resulted in drastically different outcomes. Inactivation of target-aligned striatum substantially reduced behavioral responses to all task stimuli without disrupting the ability to respond, suggesting essential roles in sensory selection. In contrast, inactivation of distractor-aligned frontal cortex increased responses to distractor stimuli, indicating essential roles in distractor inhibition. Overall, these data suggest distinct functions of frontal cortex and dorsolateral striatum in this task, despite having similar neuronal representations.

Rapid increases in cell volume reduce the size of the extracellular space (ECS) and are associated with elevated brain tissue excitability. We recently demonstrated that astrocytes, but not neurons, rapidly swell in elevated extracellular potassium (∧[K+]o) up to 26 mM. However, effects of acute astrocyte volume fluctuations on neuronal excitability in ∧[K+]o have been difficult to evaluate due to direct effects on neuronal membrane potential and generation of action potentials. Here we set out to isolate volume-specific effects occurring in ∧[K+]o on CA1 pyramidal neurons in acute hippocampal slices by manipulating cell volume while recording neuronal glutamate currents in 10.5 mM [K+]o + tetrodotoxin (TTX) to prevent neuronal firing. Elevating [K+]o to 10.5 mM induced astrocyte swelling and produced significant increases in neuronal excitability in the form of mixed α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA)/N-methyl-D-aspartate (NMDA) receptor mEPSCs and NMDA receptor-dependent slow inward currents (SICs). Application of hyperosmolar artificial cerebrospinal fluid (ACSF) by addition of mannitol in the continued presence of 10.5 mM K+ forced shrinking of astrocytes and to a lesser extent neurons, which resisted swelling in ∧[K+]o. Cell shrinking and dilation of the ECS significantly dampened neuronal excitability in 10.5 mM K+. Subsequent removal of mannitol amplified effects on neuronal excitability and nearly doubled the volume increase in astrocytes, presumably due to continued glial uptake of K+ while mannitol was present. Slower, larger amplitude events mainly driven by NMDA receptors were abolished by mannitol-induced expansion of the ECS. Collectively, our findings suggest that cell volume regulation of the ECS in elevated [K+]o is driven predominantly by astrocytes, and that cell volume effects on neuronal excitability can be effectively isolated in elevated [K+]o conditions.

The spread of a new virus has caused a worldwide effort to combat the COVID-19 pandemic. Humans, however, have experienced many viral outbreaks in the past. Historical data can help inform current analyses and decisions. Thus, this infographic compares COVID-19 with past pandemics and outbreaks to showcase similarities and differences. This can allow for a better understanding of COVID-19 in the context of past events and changing perspectives.