One of the most striking features of the hippocampal network is its ability to self-generate neuronal sequences representing temporally compressed, spatially coherent paths. These brief events, often termed "replay" in the scientific literature, are largely confined to non-exploratory states such as sleep or quiet rest. Early studies examining the content of replay noted a strong correlation between the encoded spatial information and the animal's prior behavior; thus, replay was initially hypothesized to play a role in memory formation and/or systems-level consolidation via "off-line" reactivation of previous experiences. However, recent findings indicate that replay may also serve as a memory retrieval mechanism to guide future behavior or may be an incidental reflection of pre-existing network assemblies. Here, I will review what is known regarding the content of replay events and their correlation with past and future actions, and I will discuss how this knowledge might inform or constrain models which seek to explain the circuit-level mechanisms underlying these events and their role in mnemonic processes.memory, place cells, reactivation, review, ripple| I N TR ODU C TI ONAdaptive behavior requires the brain to preserve coherent representations of experience and later extract that stored information to inform future behaviors. For decades, researchers have utilized goal-directed navigation and the brain's spatial memory system as a specific example to explore more general questions regarding memory processes (Tolman, 1948). Two discoveries in particular have prompted researchers to focus such studies on the hippocampus: (a) Human patients and animal models with damage to their medial temporal lobe (and the hippocampus in particular) display severe impairments in their ability to form new episodic and spatial memories (Morris et al., 1982;Scoville & Milner, 1957;Squire et al., 2004); and (b) individual neurons within the hippocampus represent spatial information in their firing patterns during exploration, implicating the hippocampus in the processing and storage of spatial memories (Moser et al., 2008;O'Keefe and Dostrovsky, 1971). A persistent, fundamental question within this domain is how an entire experience or spatial trajectory, which may be represented within the hippocampus by the activity of tens of thousands of neurons ordered in a precise temporal sequence, can be coherently stored within that neural network or purposefully retrieved at the exact time when the stored information would be useful for guiding future decisions.Among several lines of investigation attempting to address this question (Garner et al., 2012;Josselyn et al., 2015; Ramirez et al., 2013;Tse et al., 2007), hippocampal ripples and ripple-based "replay" have emerged as strong candidate mechanisms which may facilitate both the initial storage and later retrieval of complex, temporally ordered information about experience. Ripples are brief (50-100 ms duration), high-frequency (150-300 Hz) network oscillations within ...

In memory, the continuous flow of experience is punctuated at meaningful boundaries between one episode and the next. When salient events are separated by increasing amounts of space or time, memory systems can accommodate in two ways. One option is to increase the amount of neural resources devoted to longer event segments. The other is to maintain the same neural resources with sacrificed spatiotemporal resolution. Here we review how the spatial coding system is affected by the segmentation of space by goals and boundaries. We argue that the resolution of the place code is dictated by the amount of space encoded within periods of theta. Thus, the theta cycle is viewed as a 'neural word' that segregates segments of space and its cognitive equivalents (memory, planning). In support of this conclusion, we report that, as rats traverse a linear track, the beginning of a journey is represented at the falling phase of theta whereas the journey's end is represented on the ascending phase. The current location is represented in the temporal context of the past and future event boundaries. These results are discussed in relation to the changes in physiology observed across the longitudinal axis of the hippocampus, with a special consideration for how sequence information could be integrated by downstream 'reader' neurons.

Sharp wave ripples (SPW-Rs) represent the most synchronous population pattern in the mammalian brain. Their excitatory output affects a wide area of the cortex and several subcortical nuclei. SPW-Rs occur during ‘off-line’ states of the brain, associated with consummatory behaviors and non-REM sleep, and are influenced by numerous neurotransmitters and neuromodulators. They arise from the excitatory recurrent system of the CA3 region and the SPW-induced excitation brings about a fast network oscillation (ripple) in CA1. The spike content of SPW-Rs is temporally and spatially coordinated by a consortium of interneurons to replay fragments of waking neuronal sequences in a compressed format. SPW-Rs assist in transferring this compressed hippocampal representation to distributed circuits to support memory consolidation; selective disruption of SPW-Rs interferes with memory. Recently acquired and pre-existing information are combined during SPW-R replay to influence decisions, plan actions and, potentially, allow for creative thoughts. In addition to the widely studied contribution to memory, SPW-Rs may also affect endocrine function via activation of hypothalamic circuits. Alteration of the physiological mechanisms supporting SPW-Rs leads to their pathological conversion, “p-ripples”, which are a marker of epileptogenic tissue and can be observed in rodent models of schizophrenia and Alzheimer’s Disease. Mechanisms for SPW-R genesis and function are discussed in this review.