Lateralization of short-term memory in the frontal cortex.

Despite essentially symmetric structures in mammalian brains, the left and right hemispheres do not contribute equally to certain cognitive functions. How both hemispheres interact to cause this asymmetry remains unclear. Here, we study this question in the anterior lateral motor cortex (ALM) of mice performing five versions of a tactile-based decision-making task with a short-term memory (STM) component. Unilateral inhibition of ALM produces variable behavioral deficits across tasks, with the left, right, or both ALMs playing critical roles in STM. Neural activity and its encoding capability are similar across hemispheres, despite that only one hemisphere dominates in behavior. Inhibition of the dominant ALM disrupts encoding capability in the non-dominant ALM, but not vice versa. Variable behavioral deficits are predicted by the influence on contralateral activity across sessions, mice, and tasks. Together, these results reveal that the left and right ALM interact asymmetrically, leading to their differential contributions to STM.

A cortico-basal ganglia-thalamo-cortical channel underlying short-term memory.

Persistent activity underlying short-term memory encodes sensory information or instructs specific future movement and, consequently, has a crucial role in cognition. Despite extensive study, how the same set of neurons respond differentially to form selective persistent activity remains unknown. Here, we report that the cortico-basal ganglia-thalamo-cortical (CBTC) circuit supports the formation of selective persistent activity in mice. Optogenetic activation or inactivation of the basal ganglia output nucleus substantia nigra pars reticulata (SNr)-to-thalamus pathway biased future licking choice, without affecting licking execution. This perturbation differentially affected persistent activity in the frontal cortex and selectively modulated neural trajectory that encodes one choice but not the other. Recording showed that SNr neurons had selective persistent activity distributed across SNr, but with a hotspot in the mediolateral region. Optogenetic inactivation of the frontal cortex also differentially affected persistent activity in the SNr. Together, these results reveal a CBTC channel functioning to produce selective persistent activity underlying short-term memory.