A technique for stereotaxic recordings of neuronal activity in awake, head-restrained mice

Neurophysiological recordings of brain activity during behavior in awake animals have traditionally been performed in primates because of their evolutionary close relationship to humans and comparable behavioral skills. However, with properly designed behavioral tasks, many fundamental questions about how the brain controls behavior can also be addressed in small rodents. Today, the rapid progress in mouse neurogenetics, including the development of mouse models of human brain disorders, provides unique and unparalleled opportunities for the investigation of normal and pathological brain function. The development of experimental procedures for the recording of neuronal activity in awake and behaving mice is an important and necessary step towards neurophysiological investigation of normal and pathological mouse brain function. Here we describe a method for stereotaxic recordings of neuronal activity from head-restrained mice during fluid licking. Fluid licking is a natural and spontaneous behavior in rodents, which mice readily perform under head-restrained conditions. Using a head-restrained preparation allows recordings of well-isolated single units at multiple sites during repeated experimental sessions. Thus, a large number of neurons can be tested for their relationship with behavior and detailed spatial maps of behavior related neuronal activity can be generated as exemplified here with recordings from lick-related Purkinje cells in the cerebellum.