ABSTRACT
The optimal protocol for neuromodulation by transcranial direct current stimulation (tDCS) remains unclear. Using the rotarod paradigm, we found that mouse motor learning was enhanced by anodal tDCS (3.2 mA/cm2) during but not before or after the performance of a task. Dual-task experiments showed that motor learning enhancement was specific to the task accompanied by anodal tDCS. Studies using a mouse model of stroke induced by middle cerebral artery occlusion showed that concurrent anodal tDCS restored motor learning capability in a task-specific manner. Transcranial in vivo Ca2+ imaging further showed that anodal tDCS elevated and cathodal tDCS suppressed neuronal activity in the primary motor cortex (M1). Anodal tDCS specifically promoted the activity of task-related M1 neurons during task performance, suggesting that elevated Hebbian synaptic potentiation in task-activated circuits accounts for the motor learning enhancement. Thus, application of tDCS concurrent with the targeted behavioral dysfunction could be an effective approach to treating brain disorders.
Subject(s)
Transcranial Direct Current Stimulation/methods , Motor Cortex/physiology , Neurons , Transcranial Magnetic StimulationABSTRACT
Animal survival necessitates adaptive behaviors in volatile environmental contexts. Virtual reality (VR) technology is instrumental to study the neural mechanisms underlying behaviors modulated by environmental context by simulating the real world with maximized control of contextual elements. Yet current VR tools for rodents have limited flexibility and performance (e.g., frame rate) for context-dependent cognitive research. Here, we describe a high-performance VR platform with which to study contextual behaviors immersed in editable virtual contexts. This platform was assembled from modular hardware and custom-written software with flexibility and upgradability. Using this platform, we trained mice to perform context-dependent cognitive tasks with rules ranging from discrimination to delayed-sample-to-match while recording from thousands of hippocampal place cells. By precise manipulations of context elements, we found that the context recognition was intact with partial context elements, but impaired by exchanges of context elements. Collectively, our work establishes a configurable VR platform with which to investigate context-dependent cognition with large-scale neural recording.