Both neocortical and hippocampal networks organize the firing patterns of their neurons by prominent oscillations during sleep, but the functional role of these rhythms is not well understood. Here, we show a robust correlation of neuronal discharges between the somatosensory cortex and hippocampus on both slow and fine time scales in the mouse and rat. Neuronal bursts in deep cortical layers, associated with sleep spindles and delta waves͞ slow rhythm, effectively triggered hippocampal discharges related to fast (ripple) oscillations. We hypothesize that oscillation-mediated temporal links coordinate specific information transfer between neocortical and hippocampal cell assemblies. Such a neocortical-hippocampal interplay may be important for memory consolidation.T he means by which ensembles of neurons interact with each other for an effective transfer and storage of information are not well understood. It is generally believed that network oscillatory rhythms within and across structures support these functions (1, 2). One current working hypothesis is that information transfer at the hippocampal-neocortical interface in sleep-wake cycle is involved in the encoding and consolidation of memories (3-12). The oscillatory patterns in these structures are fundamentally different in states of waking and sleep (13-15). Attentive, exploratory behavior is characterized by neocortical fast gamma activity and hippocampal theta͞gamma oscillations (16-18). The most prominent hippocampal pattern during slow wave sleep is a transient burst of CA3-CA1 pyramidal cells associated with a sharp wave in stratum (str.) radiatum and fast field oscillation (140-to 200-Hz ripple) in the CA1 pyramidal layer (19-21). Sleep patterns of the neocortex include thalamocortical sleep spindles (12-18 Hz) and delta waves (1-4 Hz) (13,22). Whether and how these macroscopic rhythms support the coding, transfer, and consolidation of information is not understood.Recently, it has been suggested that hippocampal ripples and sleep spindles in the prefrontal cortex are temporally linked on the scale of Ϸ1 s (23). Whether neurons of the hippocampus and neocortex are involved in a more specific spatiotemporal interaction during sleep remains to be explored. To address this issue, we used multisite recording of unit and field activity in the hippocampus and somatosensory cortex. The somatosensory cortex was chosen because it is the most prominent source of sensory information in the rat (24), and, unlike the prefrontal cortex (25), it does not receive monosynaptic input from the hippocampus. Here, we demonstrate temporal coupling of neuronal activity between the somatosensory cortex and hippocampus on both slow and fine time scales and show that neocortical activity can time the occurrence of hippocampal sharp waves and ripples. Such coupling may assist linking neocortical and hippocampal cell assemblies during slow wave sleep. Materials and MethodsTen male mice (six progeny of C57B6͞J and 129S6͞SvEvTac hybrid mice and four connexin36 knockout; ref. 26;...

Summary Adult-born granule cells (GCs), a minor population of cells in the hippocampal dentate gyrus, are highly active during the first few weeks following functional integration into the neuronal network (young GCs), distinguishing them from less active older adult-born GCs and the major population of dentate GCs generated developmentally (together, old GCs). We created a transgenic mouse in which output of old GCs was specifically inhibited while leaving a substantial portion of young GCs intact. These mice exhibited enhanced or normal pattern separation between similar contexts that was reduced following removal of young GCs by X-ray irradiation. Furthermore, mutant mice exhibited deficits in rapid pattern completion. Therefore, pattern separation of similar contexts requires adult-born young GCs while old GCs are unnecessary, whereas older GCs contribute to the rapid recall by pattern completion. Our data suggest that as adult-born GCs age, their function switches from pattern separation to rapid pattern completion.

The hippocampus is an area of the brain involved in learning and memory. It contains parallel excitatory pathways referred to as the trisynaptic pathway (which carries information as follows: entorhinal cortex --> dentate gyrus --> CA3 --> CA1 --> entorhinal cortex) and the monosynaptic pathway (entorhinal cortex --> CA1 --> entorhinal cortex). We developed a generally applicable tetanus toxin-based method for transgenic mice that permits inducible and reversible inhibition of synaptic transmission and applied it to the trisynaptic pathway while preserving transmission in the monosynaptic pathway. We found that synaptic output from CA3 in the trisynaptic pathway is dispensable and the short monosynaptic pathway is sufficient for incremental spatial learning. In contrast, the full trisynaptic pathway containing CA3 is required for rapid one-trial contextual learning, for pattern completion-based memory recall, and for spatial tuning of CA1 cells.

Genetic engineering of the mouse brain allows investigators to address novel hypotheses in vivo. Because of the paucity of information on the network patterns of the mouse hippocampus, we investigated the electrical patterns in the behaving animal using multisite silicon probes and wire tetrodes. Theta (6-9 Hz) and gamma (40-100 Hz) oscillations were present during exploration and rapid eye movement sleep. Gamma power and theta power were comodulated and gamma power varied as a function of the theta cycle. Pyramidal cells and putative interneurons were phase-locked to theta oscillations. During immobility, consummatory behaviors and slow-wave sleep, sharp waves were present in cornu ammonis region CA1 of the hippocampus stratum radiatum associated with 140-200-Hz "ripples" in the pyramidal cell layer and population burst of CA1 neurons. In the hilus, large-amplitude "dentate spikes" occurred in association with increased discharge of hilar neurons. The amplitude of field patterns was larger in the mouse than in the rat, likely reflecting the higher neuron density in a smaller brain. We suggest that the main hippocampal network patterns are mediated by similar pathways and mechanisms in mouse and rat.

The importance of long-term synaptic plasticity as a cellular substrate for learning and memory is well established. By contrast, little is known about how learning and memory are regulated by voltage-gated ion channels that integrate synaptic information. We investigated this question using mice with general or forebrain-restricted knockout of the HCN1 gene, which we find encodes a major component of the hyperpolarization-activated inward current (Ih) and is an important determinant of dendritic integration in hippocampal CA1 pyramidal cells. Deletion of HCN1 from forebrain neurons enhances hippocampal-dependent learning and memory, augments the power of theta oscillations, and enhances long-term potentiation (LTP) at the direct perforant path input to the distal dendrites of CA1 pyramidal neurons, but has little effect on LTP at the more proximal Schaffer collateral inputs. We suggest that HCN1 channels constrain learning and memory by regulating dendritic integration of distal synaptic inputs to pyramidal cells.

Neural firing discharges are often temporally patterned, but it is often ambiguous as to whether the temporal features of these patterns constitute a useful code. Here we show in the mouse olfactory bulb that ensembles of projection neurons respond with complex odor- and concentration-specific dynamic activity sequences developing below and above sniffing frequency. Based on this activity, almost optimal discrimination of presented odors was possible during single sniffs, consistent with reported behavioral data. Within a sniff cycle, slower features of the dynamics alone (>100 ms resolution, including mean firing rate) were sufficient for maximal discrimination. A smaller amount of information was also observed in faster features down to 20-40 ms resolution. Therefore, mitral cell ensemble activity contains information at different timescales that could be separately or complementarily exploited by downstream brain centers to make odor discriminations. Our results also support suggestive analogies in the dynamics of odor representations between insects and mammals.

SUMMARY A widely held memory consolidation theory posits that memory of events and space is initially stored in the hippocampus (HPC) in a time-limited manner and is consolidated in the neocortex for permanent storage. Although post-training HPC lesions result in temporally graded amnesia, the precise HPC circuits and mechanisms involved in remote memory storage remain poorly understood. To investigate the role of the trisynaptic pathway in the consolidation process we employed the CA3-TeTX transgenic mouse, in which CA3 output can be specifically and inducibly controlled. We found that post-training blockade of CA3 output for up to four weeks impairs the consolidation of contextual fear memory. Moreover, in vivo hippocampal recordings revealed a reduced intrinsic frequency of CA1 ripples and a significant decrease in the experience-dependent, ripple-associated coordinated reactivation of CA1 cell pairs. Collectively, these results suggest that the post-training integrity of the trisynaptic pathway and the ripple-associated reactivation of hippocampal memory engram is crucial for memory consolidation.

The physiological roles of neuronal gap junctions in the intact brain are not known. The recent generation of the connexin-36 knock-out (Cx36 KO) mouse has offered a unique opportunity to examine this problem. Recent in vitro recordings in Cx36 KO mice suggested that Cx36 gap junction contributes to various oscillatory patterns in the theta (approximately 5-10 Hz) and gamma (approximately 30-80 Hz) frequency ranges and affects certain aspects of high-frequency (>100 Hz) patterns. However, the relevance of these pharmacologically induced patterns to the intact brain is not known. We recorded field potentials and unit activity in the CA1 stratum pyramidale of the hippocampus in the behaving wild-type (WT) and Cx36 KO mice. Fast-field "ripple" oscillations (140-200 Hz) were present in both WT and KO mice and did not differ significantly in power, intraepisode frequency, or probability of occurrence. Thus, fast-field oscillations either may not require electrical synapses or may be mediated by a hitherto unknown class of gap junctions. Theta oscillations, recorded during either wheel running or rapid eye movement sleep, were not different either. However, the power in the gamma frequency band and the magnitude of theta-phase modulation of gamma power were significantly decreased in KO mice compared with WT controls during wheel running. This suggests that Cx36 interneuronal gap junctions selectively contribute to gamma oscillations.