Hippocampal theta (5-10 Hz) and gamma (35-85 Hz) oscillations depend on an inhibitory network of GABAergic interneurons. However, the lack of methods for direct and cell-type-specific interference with inhibition has prevented better insights that help link synaptic and cellular properties with network function. Here, we generated genetically modified mice (PV-⌬␥ 2) in which synaptic inhibition was ablated in parvalbumin-positive (PV؉) interneurons. Hippocampal local field potential and unit recordings in the CA1 area of freely behaving mice revealed that theta rhythm was strongly reduced in these mice. The characteristic coupling of theta and gamma oscillations was strongly altered in PV-⌬␥ 2 mice more than could be accounted for by the reduction in theta rhythm only. Surprisingly, gamma oscillations were not altered. These data indicate that synaptic inhibition onto PV؉ interneurons is indispensable for theta-and its coupling to gamma oscillations but not for rhythmic gammaactivity in the hippocampus. Similar alterations in rhythmic activity were obtained in a computational hippocampal network model mimicking the genetic modification, suggesting that intrahippocampal networks might contribute to these effects.compartmental model ͉ GABA ͉ GABAA receptor ͉ knockout ͉ network synchrony

Neurons form transiently stable assemblies that may underlie cognitive functions, including memory formation. In most brain regions, coherent activity is organized by network oscillations that involve sparse firing within a well-defined minority of cells. Despite extensive work on the underlying cellular mechanisms, a fundamental question remains unsolved: how are participating neurons distinguished from the majority of nonparticipators? We used physiological and modeling techniques to analyze neuronal activity in mouse hippocampal slices during spontaneously occurring high-frequency network oscillations. Network-entrained action potentials were exclusively observed in a defined subset of pyramidal cells, yielding a strict distinction between participating and nonparticipating neurons. These spikes had unique properties, because they were generated in the axon without prior depolarization of the soma. GABA A receptors had a dual role in pyramidal cell recruitment. First, the sparse occurrence of entrained spikes was accomplished by intense perisomatic inhibition. Second, antidromic spike generation was facilitated by tonic effects of GABA in remote axonal compartments. Ectopic spike generation together with strong somatodendritic inhibition may provide a cellular mechanism for the definition of oscillating assemblies.antidromic action potentials | CA1 pyramidal cells | interneurons | ripples I nformation processing in neuronal networks has been proposed to rely on coordinated patterns of activity in transiently stable neuronal assemblies (1). Such patterns underlie different cognitive or behavioral tasks including motor patterns (2), perception (3), and spatial cognition (4). The functional coupling of neurons within distributed assemblies is believed to be organized by network oscillations that cover multiple frequency bands and follow distinct mechanisms (5). However, it is still unclear how neurons within an activated assembly are distinguished from the majority of nonparticipating cells. This distinction is essential for maintaining sparse and stable neural representations (6).Spatial memory formation in rodents has become an important model system for studying neuronal representations within networks. Place-selective neurons of the hippocampus are sequentially activated during exploration of an environment and reactivated during subsequent resting periods (7), indicating the formation of stable assemblies. During reactivation, temporal and spatial precision of pyramidal cell firing is organized by propagating sharp waves with superimposed high-frequency network oscillations [sharp wave ripple complexes (SPW-Rs)] (8, 9). While traveling through the CA1 area, each SPW-R recruits only a few selected cells to fire action potentials (8), whereas the majority of nonparticipating cells is silent, ensuring clear signal to noise separation (10). The mechanisms underlying this functional distinction between participating and nonparticipating cells are, however, unclear. Recordings in vivo (11) and in vitro (12) have ...

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.

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