Rhythmic activation of excitatory neurons in the mouse frontal cortex improves the prefrontal cortex–mediated cognitive function

Abstract

The prefrontal cortex (PFC) plays essential roles in cognitive processes. Previous studies have suggested the layer and the cell type–specific activation for cognitive enhancement. However, the mechanism by which a temporal pattern of activation affects cognitive function remains to be elucidated. Here, we investigated whether the specific activation of excitatory neurons in the superficial layers mainly in the PFC according to a rhythmic or nonrhythmic pattern could modulate the cognitive functions of normal mice. We used a C128S mutant of channelrhodopsin 2, a step function opsin, and administered two light illumination patterns: (i) alternating pulses of blue and yellow light for rhythmic activation or (ii) pulsed blue light only for nonrhythmic activation. Behavioral analyses were performed to compare the behavioral consequences of these two neural activation patterns. The alternating blue and yellow light pulses, but not the pulsed blue light only, significantly improved spatial working memory and social recognition without affecting motor activity or the anxiety level. These results suggest that the rhythmic, but not the nonrhythmic, activation could enhance cognitive functions. This study indicates that not only the population of neurons that are activated but also the pattern of activation plays a crucial role in the cognitive enhancement.

New Insights into Brain Imaging Methods for Rehabilitation of Brain Diseases

“…In clinical practice, cognitive-motor therapy, which emphasizes perceptual input and cognitive-driven movement, has been increasingly practiced clinically in improving walking ability in patients with cerebral infarction, especially in tasks requiring attention and processing speed, such as multitasking and gait adaptation tasks (Montero-Odasso et al, 2012). Some studies demonstrated the importance of cortical function for locomotion, as well as a greater emphasis on some methods to improve motor function by activating cognitive processes in the cortex (Fritz et al, 2015;Pothier et al, 2018;Hazra et al, 2022). In addition, cognitivemotor training, in which a cognitive task is performed alongside motor training, can more effectively strengthen the functional brain network connections between motor-cognitive brain areas and facilitate the activation of the cerebral cortex, thus promoting brain functional network remodeling and improving the patient's functional impairment (Caetano et al, 2017;Pang et al, 2018).…”

Prefrontal activation in response to a plantar contact task under open and closed eye conditions in patients with cerebral infarction

“…In clinical practice, cognitive-motor therapy, which emphasizes perceptual input and cognitive-driven movement, has been increasingly practiced clinically in improving walking ability in patients with cerebral infarction, especially in tasks requiring attention and processing speed, such as multitasking and gait adaptation tasks ( Montero-Odasso et al, 2012 ). Some studies demonstrated the importance of cortical function for locomotion, as well as a greater emphasis on some methods to improve motor function by activating cognitive processes in the cortex ( Fritz et al, 2015 ; Pothier et al, 2018 ; Hazra et al, 2022 ). In addition, cognitive-motor training, in which a cognitive task is performed alongside motor training, can more effectively strengthen the functional brain network connections between motor-cognitive brain areas and facilitate the activation of the cerebral cortex, thus promoting brain functional network remodeling and improving the patient’s functional impairment ( Caetano et al, 2017 ; Pang et al, 2018 ).…”