SUMMARY Although it has been tacitly assumed that the hippocampus exerts an influence on neocortical networks, the mechanisms of this process are not well understood. We examined whether and how hippocampal theta oscillations affect neocortical assembly patterns by recording populations of single cells and transient gamma oscillations in multiple cortical regions, including the somatosensory area and prefrontal cortex in behaving rats and mice. Laminar analysis of neocortical gamma bursts revealed multiple gamma oscillators of varying frequency and location, which were spatially confined and synchronized local groups of neurons. A significant fraction of putative pyramidal cells and interneurons as well as localized gamma oscillations in all recorded neocortical areas were phase-biased by the hippocampal theta rhythm. We hypothesize that temporal coordination of neocortical gamma oscillators by hippocampal theta is a mechanism by which information contained in spatially widespread neocortical assemblies can be synchronously transferred to the associative networks of the hippocampus.

Brain systems communicate by means of neuronal oscillations at multiple temporal and spatial scales. In anesthetized rats, we find that neocortical "slow" oscillation engages neurons in prefrontal, somatosensory, entorhinal, and subicular cortices into synchronous transitions between UP and DOWN states, with a corresponding bimodal distribution of their membrane potential. The membrane potential of hippocampal granule cells and CA3 and CA1 pyramidal cells lacked bimodality, yet it was influenced by the slow oscillation in a region-specific manner. Furthermore, in both anesthetized and naturally sleeping rats, the cortical UP states resulted in increased activity of dentate and most CA1 neurons, as well as the highest probability of ripple events. Yet, the CA3-CA1 network could self-organize into gamma bursts and occasional ripples during the DOWN state. Thus, neo/paleocortical and hippocampal networks periodically reset, self-organize, and temporally coordinate their cell assemblies via the slow oscillation.

The hippocampal formation is believed to be critical for the encoding, consolidation, and retrieval of episodic memories. Yet, how these processes are supported by the anatomically diverse hippocampal networks is still unknown. To examine this issue, we tested rats in a hippocampus-dependent delayed spatial alternation task on a modified T maze while simultaneously recording local field potentials from dendritic and somatic layers of the dentate gyrus, CA3, and CA1 regions by using high-density, 96-site silicon probes. Both the power and coherence of gamma oscillations exhibited layer-specific changes during task performance. Peak increases in the gamma power and coherence were found in the CA3-CA1 interface on the maze segment approaching the T junction, independent of motor aspects of task performance. These results show that hippocampal networks can be dynamically coupled by gamma oscillations according to specific behavioral demands. Based on these findings, we propose that gamma oscillations may serve as a physiological mechanism by which CA3 output can coordinate CA1 activity to support retrieval of hippocampusdependent memories.hippocampus ͉ local field potential ͉ retrieval ͉ synchrony B ased primarily on lesion studies, a consensus has emerged that the hippocampal formation is critical for episodic memories (1-3). In accord with lesion studies, the firing patterns of hippocampal and entorhinal neurons exhibit prospective and retrospective coding of episodic information (4-7). However, the specific roles of the various hippocampal subregions (8) responsible for encoding, consolidation, and retrieval of memory traces have been long debated. Computational models (9-12) have postulated the autoassociative recurrent network of the CA3 region as a suitable substrate for storing memories, which could be subsequently recalled via replay from CA3 to CA1. Circumscribed lesions in animals (13, 14) and genetic manipulations (15) also support the view that the integrity of the CA3 region is crucial in memory retrieval, but little is known about the physiological mechanisms of CA3-CA1 coordination that might support this process.Although recordings from multiple single neurons can assess the output representations of a network, the currently available large-scale unit recording methods do not have the ability to effectively monitor how information transfer is coordinated across several neuronal networks (16). On the other hand, although local field potentials (LFPs) lack single-neuron resolution, they reflect the temporal synchrony of local afferent activity and can effectively detect the changing modes of operation in local circuits (17)(18)(19). For example, synchronization of neuronal activity into coherent gamma-frequency oscillations can serve to bind representations (20, 21) and couple hippocampal and rhinal cortices during successful formation of declarative memories (22). To examine how regional networks within the hippocampal formation are dynamically coordinated during the retrieval process, we recorded LFP...

Summary Hippocampal sharp waves (SPW) and associated fast (‘ripple’) oscillations in the CA1 region are among the most synchronous physiological patterns in the mammalian brain. Using two-dimensional arrays of electrodes for recording local field potentials and unit discharges in freely moving rats, we studied the emergence of ripple oscillations (140–220 Hz) and compared their origin and cellular-synaptic mechanisms with fast gamma oscillations (90–140 Hz). We show that (a) hippocampal SPW-Rs and fast gamma oscillations are quantitatively distinct patterns but involve the same networks and share similar mechanisms, (b) both the frequency and magnitude of fast oscillations is positively correlated with the magnitude of SPWs, (c) during both ripples and fast gamma oscillations the frequency of network oscillation is higher in CA1 than in CA3, (d) SPWs and associated firing of neurons are synchronous in the dorsal hippocampus and dorso-medial entorhinal cortex but ripples are confined to the CA1 pyramidal layer and its downstream targets and (e) the emergence of CA3 population bursts, a prerequisite for SPW-ripples, is biased by activity patterns in the dentate gyrus and entorhinal cortex, with highest probability of ripples associated with an ‘optimum’ level of dentate gamma power. We hypothesize that each hippocampal subnetwork possesses distinct resonant properties, tuned by the magnitude of the excitatory drive.

Cannabinoids impair hippocampus-dependent memory in both humans and animals, but the network mechanisms responsible for this effect are unknown. Here we show that the cannabinoids Delta(9)-tetrahydrocannabinol and CP55940 decreased the power of theta, gamma and ripple oscillations in the hippocampus of head-restrained and freely moving rats. These effects were blocked by a CB1 antagonist. The decrease in theta power correlated with memory impairment in a hippocampus-dependent task. By simultaneously recording from large populations of single units, we found that CP55940 severely disrupted the temporal coordination of cell assemblies in short time windows (<100 ms) yet only marginally affected population firing rates of pyramidal cells and interneurons. The decreased power of local field potential oscillations correlated with reduced temporal synchrony but not with firing rate changes. We hypothesize that reduced spike timing coordination and the associated impairment of physiological oscillations are responsible for cannabinoid-induced memory deficits.