The hippocampus is critical for spatial learning and memory. Hippocampal neurons in awake animals exhibit place field activity that encodes current location, as well as sharp-wave ripple (SWR) activity during which representations based on past experiences are often replayed. The relationship between these patterns of activity and the memory functions of the hippocampus is poorly understood. We interrupted awake SWRs in animals learning a spatial alternation task. We observed a specific learning and performance deficit that persisted throughout training. This deficit was associated with awake SWR activity, as SWR interruption left place field activity and post-experience SWR reactivation intact. These results provide a link between awake SWRs and hippocampal memory processes, which suggests that awake replay of memory-related information during SWRs supports learning and memory-guided decision-making.

The development of microelectrodes capable of safely stimulating and recording neural activity is a critical step in the design of many prosthetic devices, brain-machine interfaces, and therapies for neurologic or nervous-system-mediated disorders. Metal electrodes are inadequate prospects for the miniaturization needed to attain neuronal-scale stimulation and recording because of their poor electrochemical properties, high stiffness, and propensity to fail due to bending fatigue. Here we demonstrate neural recording and stimulation using carbon nanotube (CNT) fiber electrodes. In vitro characterization shows that the tissue contact impedance of CNT fibers is remarkably lower than that of state-of-the-art metal electrodes, making them suitable for recording single-neuron activity without additional surface treatments. In vivo chronic studies in parkinsonian rodents show that CNT fiber microelectrodes stimulate neurons as effectively as metal electrodes with 10 times larger surface area, while eliciting a significantly reduced inflammatory response. The same CNT fiber microelectrodes can record neural activity for weeks, paving the way for the development of novel multifunctional and dynamic neural interfaces with long-term stability.

Hippocampal place cells are key to episodic memories. How these cells participate in memory retrieval remains unclear. Here, after rats acquired a fear memory by receiving mild foot-shocks at a shock zone of a track, we analyzed place cells when the animals were placed back to the track and displayed an apparent memory retrieval behavior: avoidance of the shock zone. We found that place cells representing the shock zone were reactivated, despite the fact that the animals did not enter the shock zone. This reactivation occurred in ripple-associated awake replay of place cell sequences encoding the paths from the animal’s current positions to the shock zone, but not in place cell sequences within individual cycles of theta oscillation. The result reveals a specific place cell pattern underlying the inhibitory avoidance behavior and provides strong evidence for the involvement of awake replay in fear memory retrieval.

Hippocampal information processing is often described as two-state, with a place cell state during movement and a reactivation state during stillness. Relatively little is known about how the network transitions between these different patterns of activity during exploration. Here we show that hippocampal network changes quickly and continuously as animals explore and become familiar with initially novel places. We measured the relationship between moment-by-moment changes in behavior and information flow through hippocampal output area CA1 in rats. We examined local field potential (LFP) patterns, evoked potentials and ensemble spiking and found evidence suggestive of a smooth transition from strong CA3 drive of CA1 activity at low speeds to entorhinal cortical drive of CA1 activity at higher speeds. These changes occurred with changes in behavior on a timescale of less than a second, suggesting a continuous modulation of information processing in the hippocampal circuit as a function of behavioral state.