Pattern completion through phase coding in population neurodynamics.

This article presents an alternative phase coding mechanism for Freeman's KIII model of population neurodynamics. Motivated by experimental evidence that supports the existence of a neural code based on synchronous oscillations, we propose an analogy between synchronization in neural populations and phase locking in KIII channels. An efficient method is proposed to extract phase differences across granule channels from their state-space trajectories. First, the scale invariance of the KIII model with respect to phase information is established. The phase code is then compared against the conventional amplitude code in terms of their bit-wise and across-fiber pattern recovery capabilities using decision-theoretic principles and a Hamming-distance classifier. Graph isomorphism in the Hebbian connections is exploited to perform an exhaustive evaluation of patterns on an 8-channel KIII model. Simulation results show that phase information outperforms amplitude information in the recovery of incomplete or corrupted stimuli.     

Propagation of specific network patterns through the mouse hippocampus

Network oscillations bind neurons into transient assemblies with coherent activity, enabling temporal coding. In the mammalian hippocampus, spatial relationships are represented by sequences of action potentials of place cells. Such patterns are established during memory acquisition and are re-played during sharp wave-ripple complexes in CA1 in subsequent sleep episodes. These events originate in CA3 and travel towards CA1 and downstream cortical areas. It is unclear, however, whether specific sequences of ripple-associated firing are solely defined within the CA1 network or whether these patterns are directly entrained by preceding activities of neurons within CA3. Using a model of sharp wave-ripple oscillations (SPW-R) in mouse hippocampal slices we analyzed the propagation of these signals between CA3 and CA1. We found tight coupling between high-frequency network activity in CA3 and CA1. Propagation of ripples through the hippocampal loop maintained precise temporal relationships at the network and cellular level, as indicated by coupling of field potentials, multiunit and single cell activity between major portions of CA3 and CA1. Moreover, SPW-R-like activity in CA1 could be elicited by electrical stimulation within area CA3 while antidromic activation of CA1 failed to induce organized high-frequency oscillations. Our data show that the specificity of neuronal assemblies is maintained with cell-to-cell precision while SPW-R propagate along the hippocampal loop.     

Here and now: How time segments may become events in the hippocampus

The hippocampal formation is believed to play a central role in memory functions related to the representation of events. Events are usually considered as temporally bounded processes, in contrast to the continuous nature of sensory signal flow they originate from. Events are then organized and stored according to behavioral relevance and are used to facilitate prediction of similar events. In this paper we are interested in the kind of representation of sensory signals that allows for detecting and/or predicting events. Based on new results on the identification problem of linear hidden processes, we propose a connectionist network with biologically sound parameter tuning that can represent causal relationships and define events. Interestingly, the wiring diagram of our architecture not only resembles the gross anatomy of the hippocampal formation (including the entorhinal cortex), but it also features similar spatial distribution functions of activity (localized and periodic, ‘grid-like’ patterns) as found in the different parts of the hippocampal formation. We shortly discuss how our model corresponds to different theories on the role of the hippocampal formation in forming episodic memories or supporting spatial navigation. We speculate that our approach may constitute a step toward a unified theory about the functional role of the hippocampus and the structure of memory representations.     

Long-Range Respiratory and Theta Oscillation Networks Depend on Spatial Sensory Context

Neural oscillations can couple networks of brain regions, especially at lower frequencies. The nasal respiratory rhythm, which elicits robust olfactory bulb oscillations, has been linked to episodic memory, locomotion, and exploration, along with widespread oscillatory coherence. The piriform cortex is implicated in propagating the olfactory-bulb-driven respiratory rhythm, but this has not been tested explicitly in the context of both hippocampal theta and nasal respiratory rhythm during exploratory behaviors. We investigated systemwide interactions during foraging behavior, which engages respiratory and theta rhythms. Local field potentials from the olfactory bulb, piriform cortex, dentate gyrus, and CA1 of hippocampus, primary visual cortex, and nasal respiration were recorded simultaneously from male rats. We compared interactions among these areas while rats foraged using either visual or olfactory spatial cues. We found high coherence during foraging compared with home cage activity in two frequency bands that matched slow and fast respiratory rates. Piriform cortex and hippocampus maintained strong coupling at theta frequency during periods of slow respiration, whereas other pairs showed coupling only at the fast respiratory frequency. Directional analysis shows that the modality of spatial cues was matched to larger influences in the network by the respective primary sensory area. Respiratory and theta rhythms also coupled to faster oscillations in primary sensory and hippocampal areas. These data provide the first evidence of widespread interactions among nasal respiration, olfactory bulb, piriform cortex, and hippocampus in awake freely moving rats, and support the piriform cortex as an integrator of respiratory and theta activity.SIGNIFICANCE STATEMENT Recent studies have shown widespread interactions between the nasally driven respiratory rhythm and neural oscillations in hippocampus and neocortex. With this study, we address how the respiratory rhythm interacts with ongoing slow brain rhythms across olfactory, hippocampal, and visual systems in freely moving rats. Patterns of network connectivity change with behavioral state, with stronger interactions at fast and slow respiratory frequencies during foraging as compared with home cage activity. Routing of interactions between sensory cortices depends on the modality of spatial cues present during foraging. Functional connectivity and cross-frequency coupling analyses suggest strong bidirectional interactions between olfactory and hippocampal systems related to respiration and point to the piriform cortex as a key area for mediating respiratory and theta rhythms.     

Differential propagation of ripples along the proximodistal and septotemporal axes of dorsal CA1 of rats

The functional connectivity of the hippocampus with its primary cortical input, the entorhinal cortex, is organized topographically. In area CA1 of the hippocampus, this leads to different functional gradients along the proximodistal and septotemporal axes of spatial/sensory responsivity and spatial resolution respectively. CA1 ripples, a network phenomenon, allow us to test whether the hippocampal neural network shows corresponding gradients in functional connectivity along the two axes. We studied the occurrence and propagation of ripples across the entire proximodistal axis along with a comparable spatial range of the septotemporal axis of dorsal CA1. We observed that ripples could occur at any location, and their amplitudes were independent of the tetrode location along the proximodistal and septotemporal axes. When a ripple was detected on a particular tetrode (“reference tetrode”), however, the probability of cooccurrence of ripples and ripple amplitude observed on the other tetrodes decreased as a function of distance from the reference tetrode. This reduction was greater along the proximodistal axis than the septotemporal axis. Furthermore, we found that ripples propagate primarily along the proximodistal axis. Thus, over a spatial scale of ～1.5 mm, the network is anisotropic along the two axes, complementing the topographically organized cortico‐hippocampal connections.     

Transient 23-30 Hz oscillations in mouse hippocampus during exploration of novel environments

The hippocampus is a key brain structure for the encoding of new experiences and environments. Hippocampal activity shows distinct oscillatory patterns, but the relationships between oscillations and memory are not well understood. Here we describe bursts of hippocampal approximately 23-30 Hz (beta2) oscillations in mice exploring novel, but not familiar, environments. In marked contrast to the relatively invariant approximately 8 Hz theta rhythm, beta2 power was weak during the very first lap of the novel environment, increased sharply as the mice reencountered their start point, then persisted for only a few minutes. Novelty-evoked oscillations reflected precise synchronization of individual neurons, and participating pyramidal cells showed a selective enhancement of spatial specificity. Through focal viral manipulations, we found that novelty-evoked oscillations required functional NMDA receptors in CA3, a subregion critical for fast oscillations in vitro. These findings suggest that beta2 oscillations indicate a hippocampal dynamic state that facilitates the formation of unique contextual representations.     

Human hippocampal theta oscillations and the formation of episodic memories

The importance of the hippocampal theta oscillation (4-8 Hz) to memory formation has been well-established through studies in animals, prompting researchers to propose comprehensive theories of memory and learning that rely on theta oscillations for integrating information in the hippocampus and neocortex. Yet, empirical evidence for the importance of 4-8 Hz hippocampal theta oscillations to memory formation in humans is equivocal at best. To clarify this apparent interspecies discrepancy, we recorded intracranial EEG (iEEG) data from 237 hippocampal electrodes in 33 neurosurgical patients as they performed an episodic memory task. We identified two distinct patterns of hippocampal oscillations, at ～3 and ～8 Hz, which are at the edges of the traditional 4-8 Hz human theta band. The 3 Hz "slow-theta" oscillation exhibited higher power during successful memory encoding and was functionally linked to gamma oscillations, but similar patterns were not present for the 8 Hz "fast-theta" oscillation. For episodic memory, slow-theta oscillations in the human hippocampus appear to be analogous to the memory-related theta oscillations observed in animals. Both fast-theta and slow-theta oscillations exhibit evidence of phase synchrony with oscillations in the temporal cortex. We discuss our findings in the context of recent research on the electrophysiology of human memory and spatial navigation, and explore the implications of this result for theories of cortico-hippocampal communication.     

Functional differentiation in the hippocampus

The hippocampus is critically involved in certain kinds of memory. During memory formation, it may operate as an integrated unit, or isolated parts may be responsible for different functions. Recent evidence suggests that the hippocampus is functionally differentiated along its dorsoventral (septotemporal) axis. The cortical and subcortical connections of the dorsal and ventral hippocampus are different, with information derived from the sensory cortices entering mainly in the dorsal two-thirds or three-quarters of the dentate gyrus. Rats can acquire a spatial navigation task if small tissue blocks are spared within this region, but equally large blocks at the ventral end are not capable of supporting spatial learning. In primates, the posterior hippocampus (corresponding to the dorsal hippocampus of rodents) appears to be more important than anterior areas for encoding of spatial memory and certain forms of nonspatial memory. The ventral (or anterior) hippocampal formation is to some extent disconnected from the rest of the structure both in terms of intrahippocampal and extrahippocampal connections and may be performing functions that are qualitatively different from, and independent of, those of the dorsal hippocampal formation. Hippocampus 1998;8:608–619. © 1998 Wiley-Liss, Inc.     

Spatial navigation and causal analysis in a brain-based device modeling cortical-hippocampal interactions

We describe Darwin X, a physical device that interacts with a real environment, whose behavior is guided by a simulated nervous system incorporating aspects of the detailed anatomy and physiology of the hippocampus and its surrounding regions. This brain-based device integrates cues from its environment and solves a spatial memory task. The responses of simulated neuronal units in the hippocampal areas during its exploratory behavior are comparable to place cells in the rodent hippocampus and emerged by associating sensory cues during exploration. To identify different functional hippocampal pathways and their influence on behavior, we employed a time series analysis that distinguishes causal interactions within and between simulated hippocampal and neocortical regions while the device is engaged in a spatial memory task. Our analysis identified different functional pathways within the neural simulation and prompts novel predictions about the influence of the perforant path, the trisynaptic loop and hippocampal-cortical interactions on place cell activity and behavior during navigation. Moreover, this causal time series analysis may be useful in analyzing networks in general.     

Storage, recall, and novelty detection of sequences by the hippocampus: elaborating on the SOCRATIC model to account for normal and aberrant effects of dopamine.

In order to understand how the molecular or cellular defects that underlie a disease of the nervous system lead to the observable symptoms, it is necessary to develop a large-scale neural model. Such a model must specify how specific molecular processes contribute to neuronal function, how neurons contribute to network function, and how networks interact to produce behavior. This is a challenging undertaking, but some limited progress has been made in understanding the memory functions of the hippocampus with this degree of detail. There is increasing evidence that the hippocampus has a special role in the learning of sequences and the linkage of specific memories to context. In the first part of this paper, we review a model (the SOCRATIC model) that describes how the dentate and CA3 hippocampal regions could store and recall memory sequences in context. A major line of evidence for sequence recall is the "phase precession" of hippocampal place cells. In the second part of the paper, we review the evidence for theta-gamma phase coding. According to a framework that incorporates this form of coding, the phase precession is interpreted as cued recall of a discrete sequence of items from long-term memory. The third part of the paper deals with the issue of how the hippocampus could learn memory sequences. We show that if multiple items can be active within a theta cycle through the action of a short-term "buffer," NMDA-dependent plasticity can lead to the learning of sequences presented at realistic item separation intervals. The evidence for such a buffer function is reviewed. An important underlying issue is whether the hippocampal circuitry is configured differently for learning and recall. We argue that there are indeed separate states for learning and recall, but that both involve theta oscillations, albeit in possibly different forms. This raises the question of how neuromodulatory input might switch the hippocampus between learning and recall states and more generally how different neuromodulatory inputs reconfigure the hippocampus for different functions. In the fifth part of this paper we review our studies of dopamine and dopamine/NMDA interactions in the control of synaptic function. Our results show that dopamine dramatically reduces the direct cortical input to CA1 (the perforant path input), while having little effect on the input from CA3. In order to interpret the functional consequences of this pathway-specific modulation, it is necessary to understand the function of CA1 and the role of dopaminergic input from the ventral tegmental area (VTA). In the sixth part of this paper we consider several possibilities and address the issue of how dopamine hyperfunction or NMDA hypofunction, abnormalities that may underlie schizophrenia, might lead to the symptoms of the disease. Relevant to this issue is the demonstrated role of the hippocampus in novelty detection, a function that is likely to depend on sequence recall by the hippocampus. Novelty signals are generated when reality does not match the expectations generated by sequence recall. One possible site for computing mismatch is CA1, since it receives predictions from CA3 and sensory "reality" via the perforant path. Our data suggest that disruption of this comparison would be expected under conditions of dopamine hyperfunction or NMDA hypofunction. Also relevant is the fact that the VTA, which fires in response to novelty, may both depend on hippocampal-dependent novelty detection processes and, in turn, affect hippocampal function. Through large-scale modeling that considers both the processes performed by the hippocampus and the neuromodulatory loops in which the hippocampus is embedded, it is becoming possible to generate working hypotheses that relate synaptic function and malfunction to behavior.     

Integration of the sensory inputs to place cells: what, where, why, and how?

The hippocampal place cells are a highly multimodal class of neurons, receiving information from many different sensory sources to correctly localize their firing to restricted regions of an environment. Evidence suggests that the sensory information is processed upstream of the hippocampus, to extract both angular and linear metric information, and also contextual information. These various kinds of information need to be integrated for coherent firing fields to be generated, and the present article reviews recent evidence concerning how this occurs. It is concluded that there is a functional dissociation of the cortical inputs, with one class of incoming information comprising purely metric information concerning distance and orientation, probably routed via the grid cells and head direction cells. The other class of information is much more heterogeneous and serves, at least in part, to contextualize the spatial inputs so as to provide a unique representation of the place the animal is in. Evidence from remapping studies suggests that the metric and contextual inputs interact upstream of the place cells, perhaps in entorhinal cortex. A full understanding of the generation of the hippocampal place representation will require elucidation of the representational functions of the afferent cortical areas.     

Advantages and detection of phase coding in the absence of rhythmicity

The encoding of information in spike phase relative to local field potential (LFP) oscillations offers several theoretical advantages over equivalent firing rate codes. One notable example is provided by place and grid cells in the rodent hippocampal formation, which exhibit phase precession—firing at progressively earlier phases of the 6–12 Hz movement‐related theta rhythm as their spatial firing fields are traversed. It is often assumed that such phase coding relies on a high amplitude baseline oscillation with relatively constant frequency. However, sustained oscillations with fixed frequency are generally absent in LFP and spike train recordings from the human brain. Hence, we examine phase coding relative to LFP signals with broadband low‐frequency (2–20 Hz) power but without regular rhythmicity. We simulate a population of grid cells that exhibit phase precession against a baseline oscillation recorded from depth electrodes in human hippocampus. We show that this allows grid cell firing patterns to multiplex information about location, running speed and movement direction, alongside an arbitrary fourth variable encoded in LFP frequency. This is of particular importance given recent demonstrations that movement direction, which is essential for path integration, cannot be recovered from head direction cell firing rates. In addition, we investigate how firing phase might reduce errors in decoded location, including those arising from differences in firing rate across grid fields. Finally, we describe analytical methods that can identify phase coding in the absence of high amplitude LFP oscillations with approximately constant frequency, as in single unit recordings from the human brain and consistent with recent data from the flying bat. We note that these methods could also be used to detect phase coding outside of the spatial domain, and that multi‐unit activity can substitute for the LFP signal. In summary, we demonstrate that the computational advantages offered by phase coding are not contingent on, and can be detected without, regular rhythmicity in neural activity.     

Hippocampal Theta Oscillations Support Successful Associative Memory Formation

Models of memory formation posit that episodic memory formation depends critically on the hippocampus, which binds features of an event to its context. For this reason, the contrast between study items that are later recollected with their associative pair versus those for which no association is made fails should reveal electrophysiological patterns in the hippocampus selectively involved in associative memory encoding. Extensive data from studies in rodents support a model in which theta oscillations fulfill this role, but results in humans have not been as clear. Here, we used an associative recognition memory procedure to identify hippocampal correlates of successful associative memory encoding and retrieval in patients (10 females and 9 males) undergoing intracranial EEG monitoring. We identified a dissociation between 2–5 Hz and 5–9 Hz theta oscillations, by which power increases in 2–5 Hz oscillations were uniquely linked with successful associative memory in both the anterior and posterior hippocampus. These oscillations exhibited a significant phase reset that also predicted successful associative encoding and distinguished recollected from nonrecollected items at retrieval, as well as contributing to relatively greater reinstatement of encoding-related patterns for recollected versus nonrecollected items. Our results provide direct electrophysiological evidence that 2–5 Hz hippocampal theta oscillations preferentially support the formation of associative memories, although we also observed memory-related effects in the 5–9 Hz frequency range using measures such as phase reset and reinstatement of oscillatory activity.SIGNIFICANCE STATEMENT Models of episodic memory encoding predict that theta oscillations support the formation of interitem associations. We used an associative recognition task designed to elicit strong hippocampal activation to test this prediction in human neurosurgical patients implanted with intracranial electrodes. The findings suggest that 2–5 Hz theta oscillatory power and phase reset in the hippocampus are selectively associated with associative memory judgments. Furthermore, reinstatement of oscillatory patterns in the hippocampus was stronger for successful recollection. Collectively, the findings support a role for hippocampal theta oscillations in human associative memory.     

Hippocampal and cortical place cell plasticity: implications for episodic memory

In humans, the hippocampus is essential for storing episodic memories. These event memories require the rapid storage of novel associations, but little is known about the cellular correlates of such rapid plasticity. We studied patterns of activity and plasticity in the CA1 region of the hippocampus and in anatomically adjacent cortical regions as rats explored a novel arm of a maze to identify the neural correlates of hippocampally dependent memory formation. We found that hippocampal place fields exhibited three phenomena that may have direct relevance to the encoding of episodic memories: (1) very rapid plasticity upon exposure to the new environment, (2) instability in representations formed after short periods of exploration, and (3) a dissociation between the stability of a hippocampal representation and the apparent familiarity of a location. In contrast, cortical regions showed less dramatic changes. Taken together, these findings suggest that hippocampal activity undergoes a period of rapid reorganization during the encoding of novel information, and that even after this reorganization is complete, areas outside the hippocampus have not yet formed stable memories.     

Disruption of hippocampal rhythms via optogenetic stimulation during the critical period for memory development impairs spatial cognition

BackgroundHippocampal oscillations play a critical role in the ontogeny of allocentric memory in rodents. During the critical period for memory development, hippocampal theta is the driving force behind the temporal coordination of neuronal ensembles underpinning spatial memory. While known that hippocampal oscillations are necessary for normal spatial cognition, whether disrupted hippocampal oscillatory activity during the critical period impairs long-term spatial memory is unknown. Here we investigated whether disruption of normal hippocampal rhythms during the critical period have enduring effects on allocentric memory in rodents.Objective/hypothesisWe hypothesized that disruption of hippocampal oscillations via artificial regulation of the medial septum during the critical period for memory development results in long-standing deficits in spatial cognition.MethodsAfter demonstrating that pan-neuronal medial septum (MS) optogenetic stimulation (465 nm activated) regulated hippocampal oscillations in weanling rats we used a random pattern of stimulation frequencies to disrupt hippocampal theta rhythms for either 1Hr or 5hr a day between postnatal (P) days 21–25. Non-stimulated and yellow light-stimulated (590 nm) rats served as controls. At P50-60 all rats were tested for spatial cognition in the active avoidance task. Rats were then sacrificed, and the MS and hippocampus assessed for cell loss. Power spectrum density of the MS and hippocampus, coherences and voltage correlations between MS and hippocampus were evaluated at baseline for a range of stimulation frequencies from 0.5 to 110 Hz and during disruptive hippocampal stimulation. Unpaired t-tests and ANOVA were used to compare oscillatory parameters, behavior and cell density in all animals.ResultsNon-selective optogenetic stimulation of the MS in P21 rats resulted in precise regulation of hippocampal oscillations with 1:1 entrainment between stimulation frequency (0.5–110 Hz) and hippocampal local field potentials. Across bandwidths MS stimulation increased power, coherence and voltage correlation at all frequencies whereas the disruptive stimulation increased power and reduced coherence and voltage correlations with most statistical measures highly significant (p < 0.001, following correction for false detection). Rats receiving disruptive hippocampal stimulation during the critical period for memory development for either 1Hr or 5hr had marked impairment in spatial learning as measured in active avoidance test compared to non-stimulated or yellow light-control rats (p < 0.001). No cell loss was measured between the blue-stimulated and non-stimulated or yellow light-stimulated controls in either the MS or hippocampus.ConclusionThe results demonstrated that robust regulation of hippocampal oscillations can be achieved with non-selective optogenetic stimulation of the MS in rat pups. A disruptive hippocampal stimulation protocol, which markedly increases power and reduces coherence and voltage correlations between the MS and hippocampus during the critical period of memory development, results in long-standing spatial cognitive deficits. This spatial cognitive impairment is not a result of optogenetic stimulation-induced cell loss.     

High‐precision magnetoencephalography for reconstructing amygdalar and hippocampal oscillations during prediction of safety and threat

Learning to associate neutral with aversive events in rodents is thought to depend on hippocampal and amygdala oscillations. In humans, oscillations underlying aversive learning are not well characterised, largely due to the technical difficulty of recording from these two structures. Here, we used high‐precision magnetoencephalography (MEG) during human discriminant delay threat conditioning. We constructed generative anatomical models relating neural activity with recorded magnetic fields at the single‐participant level, including the neocortex with or without the possibility of sources originating in the hippocampal and amygdalar structures. Models including neural activity in amygdala and hippocampus explained MEG data during threat conditioning better than exclusively neocortical models. We found that in both amygdala and hippocampus, theta oscillations during anticipation of an aversive event had lower power compared to safety, both during retrieval and extinction of aversive memories. At the same time, theta synchronisation between hippocampus and amygdala increased over repeated retrieval of aversive predictions, but not during safety. Our results suggest that high‐precision MEG is sensitive to neural activity of the human amygdala and hippocampus during threat conditioning and shed light on the oscillation‐mediated mechanisms underpinning retrieval and extinction of fear memories in humans.     

Effects of the GABA‐uptake blocker NNC‐711 on spontaneous sharp wave–ripple complexes in mouse hippocampal slices

The precise temporal and spatial activity patterns of neurons in cortical networks are organized by different state‐dependent types of network oscillations. GABAergic inhibition plays a key role in the underlying mechanisms of such oscillations and it has been suggested that the duration of widely distributed phasic inhibitory postsynaptic potentials (IPSPs) determines the frequency of the resulting network oscillation. Here, we test this hypothesis in an in vitro model of sharp wave–ripple (SPW‐R) complexes, a particularly fast pattern of network oscillations at ～200 Hz which is involved in memory consolidation. We recorded SPW‐R in mouse hippocampal slices in the absence and presence of NCC‐711, an inhibitor of GABA uptake. The resulting prolongation of IPSP resulted in reduced occurrence of SPW‐R, whereas the superimposed fast oscillations as well as the precision of rhythmic cell synchronization remained stable. Application of Diazepam which is a positive modulator of the GABA_A receptor led to consistent results. We conclude that phasic inhibition is a major regulator of network excitability in CA3 (where SPW‐Rs are generated), but does not set the frequency of hippocampal ripples. © 2013 Wiley Periodicals, Inc.     

Slow-waves in the olfactory system: an olfactory perspective on cortical rhythms

Over the past few years, it has become clear that oscillatory dynamics of cortical networks are closely involved in sensory coding, attention, memory and sleep. Although most experimental and theoretical studies have focused on the neocortex, we believe that progress in understanding cortical oscillations can be advanced by also considering the olfactory system--which shares many basic properties with the neocortex and shows similar oscillatory patterns. Besides offering the advantage of a greater experimental tractability, the olfactory cortex might prove to be instrumental in uncovering general functional principles of neocortical oscillations, by virtue of the potentially important role of olfaction during neocortical evolution. In this article, we illustrate how such an evolution-based comparative approach can provide novel insights into neocortical slow-wave sleep oscillations and their relationship to respiration.     

Hippocampal ripples as a mode of communication with cortical and subcortical areas

Hippocampal sharp wave‐ripple complexes are transient events of highly synchronous neuronal activity that typically occur during “offline” brain states. This endogenous surge of activity consists of behaviorally relevant spiking patterns, describing spatial trajectories. They have been shown to play a critical role in memory consolidation during sleep and in navigational planning during wakefulness. Beyond their local impact on the hippocampal formation, ripples also exert direct and indirect effects on target cortical and subcortical areas, which are thought to play a key role in information processing and semantic network reconfiguration. We review research into the function of hippocampal sharp waves‐ripples, with a special focus on information flow between the hippocampus and its cortical and subcortical targets. First, we briefly review seminal work establishing a causal role of ripple‐related activity in cognitive processes. We then review evidence for a functional interplay between hippocampal ripples and specific patterns of cortical and subcortical activity. Finally, we discuss the critical role of the functional coupling between ripples and other sleep rhythms, including the cortical slow oscillation and thalamocortical sleep spindles.     

Conjunctive effects of reward and behavioral episodes on hippocampal place-differential neurons of rats on a mobile treadmill

Previous studies reported context (or behavior)-dependent activities of hippocampal place cells, which are suggested to be the neural basis of episodic memory. However, it remains unclear what distinctive items these context-dependent activities encode. We investigated separately the effects of space, locomotion, and episodes with positive/negative reinforcements on activity of place-differential neurons in the hippocampal CA1 area. Rats were placed on a treadmill affixed to a motion stage translocated along a figure 8-shaped track. The track could be navigated by two different routes that shared a common central stem. The stage was paused at the start and end of the routes, where conditioned response tasks with different reinforcements were imposed. As the rats passed the common central stem, some neurons fired differently depending on the route. Comparison of hippocampal spatial firing patterns across different conditions with and without treadmill operation and/or the tasks indicated that these route-dependent spatial firing patterns were sensitive to locomotion, the tasks, and vestibular sensation or visual cues such as optic flow. The results suggest that external sensory inputs, path integration, and reinforcement context are all integrated in the hippocampus, which might provide the neural basis of episodic memory.