The hippocampus is critical for recollecting and imagining experiences. This is believed to involve voluntarily drawing from hippocampal memory representations of people, events, and places, including maplike representations of familiar environments. However, whether representations in such "cognitive maps" can be volitionally accessed is unknown. We developed a brain-machine interface to test whether rats can do so by controlling their hippocampal activity in a flexible, goal-directed, and model-based manner. We found that rats can efficiently navigate or direct objects to arbitrary goal locations within a virtual reality arena solely by activating and sustaining appropriate hippocampal representations of remote places. This provides insight into the mechanisms underlying episodic memory recall, mental simulation and planning, and imagination and opens up possibilities for high-level neural prosthetics that use hippocampal representations.

The patch-clamp technique and the whole-cell measurements derived from it have greatly advanced our understanding of the coding properties of individual neurons by allowing for a detailed analysis of their excitatory/inhibitory synaptic inputs, intrinsic electrical properties, and morphology. Because such measurements require a high level of mechanical stability they have for a long time been limited to in vitro and anesthetized preparations. Recently, however, a considerable amount of effort has been devoted to extending these techniques to awake restrained/head-fixed preparations allowing for the study of the input-output functions of neurons during behavior. In this chapter we describe a technique extending patch-clamp recordings to awake animals free to explore their environments.

Intracellular recording is an essential technique for investigating cellular mechanisms underlying complex brain functions. Despite the high sensitivity of the technique to mechanical disturbances, intracellular recording has been applied to awake, behaving, and even freely moving, animals. Here we summarize recent advances in these methods and their application to the measurement and manipulation of membrane potential dynamics for understanding neuronal computations in behaving animals.

Intracellular recording, which allows direct measurement of the membrane potential and currents of individual neurons, requires a very mechanically stable preparation and has thus been limited to in vitro and head-immobilized in vivo experiments. This restriction constitutes a major obstacle for linking cellular and synaptic physiology with animal behavior. To overcome this limitation we have developed a method for performing whole-cell recordings in freely moving rats. We constructed a miniature head-mountable recording device, with mechanical stabilization achieved by anchoring the recording pipette rigidly in place after the whole-cell configuration is established. We obtain long-duration recordings (mean of approximately 20 min, maximum 60 min) in freely moving animals that are remarkably insensitive to mechanical disturbances, then reconstruct the anatomy of the recorded cells. This head-anchored whole-cell recording technique will enable a wide range of new studies involving detailed measurement and manipulation of the physiological properties of identified cells during natural behaviors.