The excitation wave returning to the hippocampus through the entorhinal cortex can reactivate the populations of "trained" CA1 neurons during deep sleep

It is suggested that the information about a new stimulus from the neocortex is transferred to the hippocampus and forms there a transient trace in the form of a distributed pattern of modified synapses. During sleep, the neuronal populations which store this trace are reactivated and return to the neocortex the information necessary for consolidation of the permanent memory trace. A possible mechanism of the reactivation of the "learned" hippocampal neurons during memory consolidation is the reverberation of excitation in the neuronal circuits connecting the hippocampus and the entorhinal cortex. In rats, we recorded responses in hippocampal field CA1 to stimulation of the Schaffer collaterals with potentiated synapses during wakefulness and sleep. We showed that in the periods of deep sleep, after the discharge of CA1 neurons, the wave of excitation passes through the entorhinal cortex and via the perforant path fibers enters the hippocampus and the dentate gyrus, causing in the latter the discharge of neurons. The repeated discharge of the CA1 neurons develops as the result of interaction of the early wave which is returned directly via the perforant path fibers and the late wave which is returned via the Schaffer collaterals, but not through the dentate gyrus and hippocampal field CA3 (trisynaptic pathway), but, probably, through the field CA2.     

A single microcircuit with multiple functions: state dependent information processing in the hippocampus

Many neural circuits process information in multiple distinct modes. For example, the hippocampus is involved in memory encoding, retrieval, and consolidation processes. These different mnemonic computations require processing of differing balances of current sensory input and previously stored associations. Here we explore patterns of activity in hippocampal output area CA1 associated with different information processing states. We discuss the evidence linking these patterns to specific inputs to CA1 and describe behavioral factors that are related to the balance of synaptic drive. We suggest that understanding the factors that influence information flow in the hippocampal circuit could provide important new insights into how neural circuits are reconfigured on the fly to perform different functions at different times.     

A double dissociation between hippocampal subfields: differential time course of CA3 and CA1 place cells for processing changed environments

Computational theories have suggested different functions for the hippocampal subfields (e.g., CA1 and CA3) in memory. However, it has been difficult to find dissociations relevant to these hypothesized functions in investigations of the hippocampal correlates of space ("place fields") in freely behaving animals. The current study demonstrates a double dissociation between the shifts in the center of mass (COM) of the place fields that were simultaneously recorded in CA1 and CA3 when familiar cue configurations were dynamically changed over days. The COM of CA3 place fields shifted backward in the first experience of the cue-changed environment, whereas the COM of CA1 place fields did not display the backward shift until the next day. These results support the hypothesis that CA3 plays a key role in the rapid formation of representations of new spatiotemporal sequences, whereas CA1 may be more important for comparing currently experienced sequence information with stored sequences in the CA3 network.     

Hippocampal memory consolidation during sleep: a comparison of mammals and birds

The transition from wakefulness to sleep is marked by pronounced changes in brain activity. The brain rhythms that characterize the two main types of mammalian sleep, slow‐wave sleep (SWS) and rapid eye movement (REM) sleep, are thought to be involved in the functions of sleep. In particular, recent theories suggest that the synchronous slow‐oscillation of neocortical neuronal membrane potentials, the defining feature of SWS, is involved in processing information acquired during wakefulness. According to the Standard Model of memory consolidation, during wakefulness the hippocampus receives input from neocortical regions involved in the initial encoding of an experience and binds this information into a coherent memory trace that is then transferred to the neocortex during SWS where it is stored and integrated within preexisting memory traces. Evidence suggests that this process selectively involves direct connections from the hippocampus to the prefrontal cortex (PFC), a multimodal, high‐order association region implicated in coordinating the storage and recall of remote memories in the neocortex. The slow‐oscillation is thought to orchestrate the transfer of information from the hippocampus by temporally coupling hippocampal sharp‐wave/ripples (SWRs) and thalamocortical spindles. SWRs are synchronous bursts of hippocampal activity, during which waking neuronal firing patterns are reactivated in the hippocampus and neocortex in a coordinated manner. Thalamocortical spindles are brief 7–14 Hz oscillations that may facilitate the encoding of information reactivated during SWRs. By temporally coupling the readout of information from the hippocampus with conditions conducive to encoding in the neocortex, the slow‐oscillation is thought to mediate the transfer of information from the hippocampus to the neocortex. Although several lines of evidence are consistent with this function for mammalian SWS, it is unclear whether SWS serves a similar function in birds, the only taxonomic group other than mammals to exhibit SWS and REM sleep. Based on our review of research on avian sleep, neuroanatomy, and memory, although involved in some forms of memory consolidation, avian sleep does not appear to be involved in transferring hippocampal memories to other brain regions. Despite exhibiting the slow‐oscillation, SWRs and spindles have not been found in birds. Moreover, although birds independently evolved a brain region—the caudolateral nidopallium (NCL)—involved in performing high‐order cognitive functions similar to those performed by the PFC, direct connections between the NCL and hippocampus have not been found in birds, and evidence for the transfer of information from the hippocampus to the NCL or other extra‐hippocampal regions is lacking. Although based on the absence of evidence for various traits, collectively, these findings suggest that unlike mammalian SWS, avian SWS may not be involved in transferring memories from the hippocampus. Furthermore, it suggests that the slow‐oscillation, the defining feature of mammalian and avian SWS, may serve a more general function independent of that related to coordinating the transfer of information from the hippocampus to the PFC in mammals. Given that SWS is homeostatically regulated (a process intimately related to the slow‐oscillation) in mammals and birds, functional hypotheses linked to this process may apply to both taxonomic groups.     

The remote consequences of hypoxia influence in perinatal development period on structurally functional characteristics of the rat brain

The study has shown that influence of acute hypoxia in perinatal period leads to structural changes in motor and visual of the neocortex for 20 postnatal days in the form of disturbance of the structural organisation of the neocortex layers. Different fields of hippocampus in perinatal period differently react to hypoxia, and evidence of existence of a long-term perinatal hypoxia was obtained. It is established that after action of acute hypoxia in all the fields there is a cellular destruction, and thinning of pyramidal neurones layers. The most expressed cellular destruction takes place in fields CA4 and CA3. In process of augmentation, the destruction of cells remains appreciable in the field CA4, reduced in the field CA3 and not found in the field CA1; however, in fascia dentate, the destruction of granular neurones with age augmentation increases. Along with in reduction of the dimensions of cellular bodies pyramidal neurones in all fields of hippocampus takes place. Also in all fields of hippocampus, activation of astrocytic reaction occurs, more expressed in the field CA4. The hypoxia influence in the early postnatal period can affect synaptogenes, particularly the formation of giant synapses in a dentate fascia. Study of functional features of the excitatory system of such animals has shown that hypoxia can induce appreciable disturbances of behavioural responses. In rats, disturbances of inhibiting functions of the cerebral cortex, raised anxiety, and spatial learning and working memory disturbances have been noted.     

Dynamics of retrieval strategies for remote memories

Prevailing theory suggests that long-term memories are encoded via a two-phase process requiring early involvement of the hippocampus followed by the neocortex. Contextual fear memories in rodents rely on the hippocampus immediately following training but are unaffected by hippocampal lesions or pharmacological inhibition weeks later. With fast optogenetic methods, we examine the real-time contribution of hippocampal CA1 excitatory neurons to remote memory and find that contextual fear memory recall, even weeks after training, can be reversibly abolished by temporally precise optogenetic inhibition of CA1. When this inhibition is extended to match the typical time course of pharmacological inhibition, remote hippocampus dependence converts to hippocampus independence, suggesting that long-term memory retrieval normally depends on the hippocampus but can adaptively shift to alternate structures. Further revealing the plasticity of mechanisms required for memory recall, we confirm the remote-timescale importance of the anterior cingulate cortex (ACC) and implicate CA1 in ACC recruitment for remote recall.     

Increased size and stability of CA1 and CA3 place fields in HCN1 knockout mice

Hippocampal CA1 and CA3 pyramidal neuron place cells encode the spatial location of an animal through localized firing patterns called "place fields." To explore the mechanisms that control place cell firing and their relationship to spatial memory, we studied mice with enhanced spatial memory resulting from forebrain-specific knockout of the HCN1 hyperpolarization-activated cation channel. HCN1 is strongly expressed in CA1 neurons and in entorhinal cortex grid cells, which provide spatial information to the hippocampus. Both CA1 and CA3 place fields were larger but more stable in the knockout mice, with the effect greater in CA1 than CA3. As HCN1 is only weakly expressed in CA3 place cells, their altered activity likely reflects loss of HCN1 in grid cells. The more pronounced changes in CA1 likely reflect the intrinsic contribution of HCN1. The enhanced place field stability may underlie the effect of HCN1 deletion to facilitate spatial learning and memory.     

Conjunctive spatial and self-motion codes are topographically organized in the GABAergic cells of the lateral septum

The hippocampal spatial code’s relevance for downstream neuronal populations—particularly its major subcortical output the lateral septum (LS)—is still poorly understood. Here, using calcium imaging combined with unbiased analytical methods, we functionally characterized and compared the spatial tuning of LS GABAergic cells to those of dorsal CA3 and CA1 cells. We identified a significant number of LS cells that are modulated by place, speed, acceleration, and direction, as well as conjunctions of these properties, directly comparable to hippocampal CA1 and CA3 spatially modulated cells. Interestingly, Bayesian decoding of position based on LS spatial cells reflected the animal’s location as accurately as decoding using the activity of hippocampal pyramidal cells. A portion of LS cells showed stable spatial codes over the course of multiple days, potentially reflecting long-term episodic memory. The distributions of cells exhibiting these properties formed gradients along the anterior–posterior and dorsal–ventral axes of the LS, directly reflecting the topographical organization of hippocampal inputs to the LS. Finally, we show using transsynaptic tracing that LS neurons receiving CA3 and CA1 excitatory input send projections to the hypothalamus and medial septum, regions that are not targeted directly by principal cells of the dorsal hippocampus. Together, our findings demonstrate that the LS accurately and robustly represents spatial, directional as well as self-motion information and is uniquely positioned to relay this information from the hippocampus to its downstream regions, thus occupying a key position within a distributed spatial memory network.

Calcium imaging of neurons in freely behaving mice reveals how the lateral septum, the main output of the hippocampal place cells, effectively represents information about not only location, but also head direction and self-movement, and may be pivotal in sending this information to downstream brain regions.     

Formation of temporal memory requires NMDA receptors within CA1 pyramidal neurons

In humans the hippocampus is required for episodic memory, which extends into the spatial and temporal domains. Work on the rodent hippocampus has shown that NMDA receptor (NMDAR) -mediated plasticity is essential for spatial memory. Here, we have examined whether hippocampal NMDARs are also needed for temporal memory. We applied trace fear conditioning to knockout mice lacking NMDARs only in hippocampal CA1 pyramidal cells. This paradigm requires temporal processing because the conditional and unconditional stimuli are separated by 30 s (trace). We found that knockout mice failed to memorize this association but were indistinguishable from normal animals when the trace was removed. Thus, NMDARs in CA1 are crucial for the formation of memories that associate events across time.     

Ensemble place codes in hippocampus: CA1, CA3, and dentate gyrus place cells have multiple place fields in large environments

Previously we reported that the hippocampus place code must be an ensemble code because place cells in the CA1 region of hippocampus have multiple place fields in a more natural, larger-than-standard enclosure with stairs that permitted movements in 3-D. Here, we further investigated the nature of hippocampal place codes by characterizing the spatial firing properties of place cells in the CA1, CA3, and dentate gyrus (DG) hippocampal subdivisions as rats foraged in a standard 76-cm cylinder as well as a larger-than-standard box (1.8 m×1.4 m) that did not have stairs or any internal structure to permit movements in 3-D. The rats were trained to forage continuously for 1 hour using computer-controlled food delivery. We confirmed that most place cells have single place fields in the standard cylinder and that the positional firing pattern remapped between the cylinder and the large enclosure. Importantly, place cells in the CA1, CA3 and DG areas all characteristically had multiple place fields that were irregularly spaced, as we had reported previously for CA1. We conclude that multiple place fields are a fundamental characteristic of hippocampal place cells that simplifies to a single field in sufficiently small spaces. An ensemble place code is compatible with these observations, which contradict any dedicated coding scheme.     

Coincidence detection of place and temporal context in a network model of spiking hippocampal neurons

Recent advances in single-neuron biophysics have enhanced our understanding of information processing on the cellular level, but how the detailed properties of individual neurons give rise to large-scale behavior remains unclear. Here, we present a model of the hippocampal network based on observed biophysical properties of hippocampal and entorhinal cortical neurons. We assembled our model to simulate spatial alternation, a task that requires memory of the previous path through the environment for correct selection of the current path to a reward site. The convergence of inputs from entorhinal cortex and hippocampal region CA3 onto CA1 pyramidal cells make them potentially important for integrating information about place and temporal context on the network level. Our model shows how place and temporal context information might be combined in CA1 pyramidal neurons to give rise to splitter cells, which fire selectively based on a combination of place and temporal context. The model leads to a number of experimentally testable predictions that may lead to a better understanding of the biophysical basis of information processing in the hippocampus.     

海马记忆功能的神经网络模型

综合神经心理学,神经生理学、解剖学与神经网络研究的成果,提出一个海马记忆功能的神经网络模型。模型由三个神经网络所组成;海马的ＣＡ１和ＣＡ３网络和大脑皮层联合区,ＣＡ３的功能是将不同感觉输入联合起来,而ＣＡ１的作用是将它们结成一个单一的记忆。而大脑皮层则是长期记忆的部位。在ＶＡＸ１１／７５０上进行计算机仿真,仿真证明模型有近期及长期记忆功能,破坏模拟海马的部分,模型显示出与顺行性遗忘症相似的特性。在     

Theories of episodic memory

Theories of episodic memory need to specify the encoding (representing), storage, and retrieval processes that underlie this form of memory and indicate the brain regions that mediate these processes and how they do so. Representation and re-representation (retrieval) of the spatiotemporally linked series of scenes, which constitute an episode, are probably mediated primarily by those parts of the posterior neocortex that process perceptual and semantic information. However, some role of the frontal neocortex and medial temporal lobes in representing aspects of context and high-level visual object information at encoding and retrieval cannot currently be excluded. Nevertheless, it is widely believed that the frontal neocortex is mainly involved in coordinating episodic encoding and retrieval and that the medial temporal lobes store aspects of episodic information. Establishing where storage is located is very difficult and disagreement remains about the role of the posterior neocortex in episodic memory storage. One view is that this region stores all aspects of episodic memory ab initio for as long as memory lasts. This is compatible with evidence that the amygdala, basal forebrain, and midbrain modulate neocortical storage. Another view is that the posterior neocortex only gradually develops the ability to store some aspects of episodic information as a function of rehearsal over time and that this information is initially stored by the medial temporal lobes. A third view is that the posterior neocortex never stores these aspects of episodic information because the medial temporal lobes store them for as long as memory lasts in an increasingly redundant fashion. The last two views both postulate that the medial temporal lobes initially store contextual markers that serve to cohere featural information stored in the neocortex. Lesion and functional neuroimaging evidence still does not clearly distinguish between these views. Whether the feeling that an episodic memory is familiar depends on retrieving an association between a retrieved episode and this feeling, or by an attribution triggered by a priming process, is unclear. Evidence about whether the hippocampus and medial temporal lobe cortices play different roles in episodic memory is conflicting. Identifying similarities and differences between episodic memory and both semantic memory and priming will require careful componential analysis of episodic memory.     

Electrophysiologic study of the ascending connections of the hippocampus with various neocortical zones in the rabbit

In acute experiments on rabbits studies have been made on functional connections of hippocampal fields CA1 and CA3 with various zones of the neocortex. It was shown that these hippocampal structures are most closely connected with the limbic ancient associative cortex, as well as with the parietal and temporal regions. In the sensorimotor cortex, the EPs were rather irregular. Fields CA1 and CA3 exhibit different projections to the mentioned regions of the neocortex.     

The hippocampal-VTA loop: controlling the entry of information into long-term memory

In this article we develop the concept that the hippocampus and the midbrain dopaminergic neurons of the ventral tegmental area (VTA) form a functional loop. Activation of the loop begins when the hippocampus detects newly arrived information that is not already stored in its long-term memory. The resulting novelty signal is conveyed through the subiculum, accumbens, and ventral pallidum to the VTA where it contributes (along with salience and goal information) to the novelty-dependent firing of these cells. In the upward arm of the loop, dopamine (DA) is released within the hippocampus; this produces an enhancement of LTP and learning. These findings support a model whereby the hippocampal-VTA loop regulates the entry of information into long-term memory.     

Hippocampal CA3 NMDA receptors are crucial for memory acquisition of one-time experience

Lesion and pharmacological intervention studies have suggested that in both human patients and animals the hippocampus plays a crucial role in the rapid acquisition and storage of information from a novel one-time experience. However, how the hippocampus plays this role is poorly known. Here, we show that mice with NMDA receptor (NR) deletion restricted to CA3 pyramidal cells in adulthood are impaired in rapidly acquiring the memory of novel hidden platform locations in a delayed matching-to-place version of the Morris water maze task but are normal when tested with previously experienced platform locations. CA1 place cells in the mutant animals had place field sizes that were significantly larger in novel environments, but normal in familiar environments relative to those of control mice. These results suggest that CA3 NRs play a crucial role in rapid hippocampal encoding of novel information for fast learning of one-time experience.     

Prefrontal cortical activity predicts the occurrence of nonlocal hippocampal representations during spatial navigation

The receptive field of a neuron describes the regions of a stimulus space where the neuron is consistently active. Sparse spiking outside of the receptive field is often considered to be noise, rather than a reflection of information processing. Whether this characterization is accurate remains unclear. We therefore contrasted the sparse, temporally isolated spiking of hippocampal CA1 place cells to the consistent, temporally adjacent spiking seen within their spatial receptive fields (“place fields”). We found that isolated spikes, which occur during locomotion, are strongly phase coupled to hippocampal theta oscillations and transiently express coherent nonlocal spatial representations. Further, prefrontal cortical activity is coordinated with and can predict the occurrence of future isolated spiking events. Rather than local noise within the hippocampus, sparse, isolated place cell spiking reflects a coordinated cortical–hippocampal process consistent with the generation of nonlocal scenario representations during active navigation.

This study of active navigation shows that, rather than being local noise within the hippocampus, sparse, isolated place cell spiking reflects a coordinated cortical-hippocampal process consistent with the generation of non-local scenario representations.     

Spatial-area selective retrieval of multiple object–place associations in a hierarchical cognitive map formed by theta phase coding

The human cognitive map is known to be hierarchically organized consisting of a set of perceptually clustered landmarks. Patient studies have demonstrated that these cognitive maps are maintained by the hippocampus, while the neural dynamics are still poorly understood. The authors have shown that the neural dynamic “theta phase precession” observed in the rodent hippocampus may be capable of forming hierarchical cognitive maps in humans. In the model, a visual input sequence consisting of object and scene features in the central and peripheral visual fields, respectively, results in the formation of a hierarchical cognitive map for object–place associations. Surprisingly, it is possible for such a complex memory structure to be formed in a few seconds. In this paper, we evaluate the memory retrieval of object–place associations in the hierarchical network formed by theta phase precession. The results show that multiple object–place associations can be retrieved with the initial cue of a scene input. Importantly, according to the wide-to-narrow unidirectional connections among scene units, the spatial area for object–place retrieval can be controlled by the spatial area of the initial cue input. These results indicate that the hierarchical cognitive maps have computational advantages on a spatial-area selective retrieval of multiple object–place associations. Theta phase precession dynamics is suggested as a fundamental neural mechanism of the human cognitive map.     

An investigation of phase relations between theta-rhythm potentials in the neocortex and hippocampus of rabbits

Phase relations between rhythmic activity recorded from the hippocampus and from various levels of the neocortex were calculated on a two-dimensional model on the assumption of the passive spread of hippocampal activity. The calculation showed that if such a spread of activity takes place an appreciable phase shift, caused by the spatio-temporal structure of the hippocampal source of the theta-rhythm, may exist between the rhythmic components of potentials recorded from the neocortex and hippocampus. In some series of electrophysiological experiments on rabbits various consequences of the model calculations were tested. Phase relations of the theta-rhythm recorded in the neocortex and in the hippocampus in the presence of maximal correlation between cortical potentials cannot be explained, in the overwhelming majority of cases, purely by the passive spread of hippocampal activity to the surface of the neocortex.     

Attention Enhances the Retrieval and Stability of Visuospatial and Olfactory Representations in the Dorsal Hippocampus

A key question in the analysis of hippocampal memory relates to how attention modulates the encoding and long-term retrieval of spatial and nonspatial representations in this region. To address this question, we recorded from single cells over a period of 5 days in the CA1 region of the dorsal hippocampus while mice acquired one of two goal-oriented tasks. These tasks required the animals to find a hidden food reward by attending to either the visuospatial environment or a particular odor presented in shifting spatial locations. Attention to the visuospatial environment increased the stability of visuospatial representations and phase locking to gamma oscillations—a form of neuronal synchronization thought to underlie the attentional mechanism necessary for processing task-relevant information. Attention to a spatially shifting olfactory cue compromised the stability of place fields and increased the stability of reward-associated odor representations, which were most consistently retrieved during periods of sniffing and digging when animals were restricted to the cup locations. Together, these results suggest that attention selectively modulates the encoding and retrieval of hippocampal representations by enhancing physiological responses to task-relevant information.