Slow population activities (SPAs) exist in the brain and have frequencies below ϳ5 Hz. Despite SPAs being prominent in several cortical areas and serving many putative functions, their mechanisms are not well understood. We studied a specific type of in vitro GABAergic, inhibition-based SPA exhibited by C57BL/6 murine hippocampus. We used a multipronged approach consisting of experiment, simulation, and mathematical analyses to uncover mechanisms responsible for hippocampal SPAs. Our results show that hippocampal SPAs are an emergent phenomenon in which the "slowness" of the network is due to interactions between synaptic and cellular characteristics of individual fast-spiking, inhibitory interneurons. Our simulations quantify characteristics underlying hippocampal SPAs. In particular, for hippocampal SPAs to occur, we predict that individual fast-spiking interneurons should have frequency-current ( f-I) curves that exhibit a suitably sized kink where the slope of the curve decreases more abruptly in the gamma frequency range with increasing current. We also predict that these interneurons should be well connected with one another. Our mathematical analyses show that the combination of synaptic and intrinsic conditions, as predicted by our simulations, promotes network multistability. Population slow timescales occur when excitatory fluctuations drive the network between different stable network firing states. Since many of the parameters we use are extracted from experiments and subsequent measurements of experimental f-I curves of fast-spiking interneurons exhibit characteristics as predicted, we propose that our network models capture a fundamental operating mechanism in biological hippocampal networks.

The rate of the nuclear reaction 3 He + µ − → 3 H + γ + νµ has been calculated using both the elementary particle model (EPM) approach and the impulse approximation (IA) approach. Using the EPM approach, the exclusive statistical radiative muon capture (RMC) rate for photon energy greater than 57 MeV is found to be 0.245 s −1 and the ordinary muon capture (OMC) rate to be 1503 s −1 . The IA calculation exhibits a slight dependence on the type of trinucleon wave functions used. The difference between the IA and EPM calculation is larger for RMC than for OMC. To resolve the difference between the two approaches a more detailed investigation including meson exchange corrections will be required.23. 40.-s, 21.45.+v, 13.10.+q, 24.80.+y

We have assessed the balance of excitation and inhibition in in vitro rodent hippocampal slices exhibiting spontaneous, basal sharp waves (bSPWs). A defining signature of a network exhibiting bSPWs is the rise and fall in local field activities with frequencies ranging from 0.5 to 4.5 Hz. This variation of extracellular local field activities manifests at the intracellular level as postsynaptic potentials (PSPs). In correspondence with the local field bSPWs, we consider "sparse" and "synchronous" parts of bSPWs at the intracellular level. We have used intracellular data of bSPW-associated PSPs together with mathematical extraction techniques to quantify the mean and variance of synaptic conductances that a neuron experiences during bSPW episodes. We find that inhibitory conductances dominate in pyramidal cells and in a putative interneuron, and that inhibitory variances are much greater than excitatory ones during synchronous parts of bSPWs. Specifically, we find that there is at least a twofold increase in inhibitory conductance dominance from "sparse" to "synchronous" bSPW states and that this transition is associated with inhibitory fluctuations of greater than 10% of the change in mean inhibitory conductance. On the basis of our findings, we suggest that such inhibitory fluctuations during transition may be a physiological feature of systems expressing such population activities. In summary, our results provide a quantified basis for understanding the interaction of excitatory and inhibitory neuronal subpopulations in bSPW activities.

How focal seizures initiate and evolve in human neocortex remains a fundamental problem in neuroscience. Here, we use biophysical neuronal network models of neocortical patches to study how the interaction between inhibition and extracellular potassium ([K+]o) dynamics may contribute to different types of focal seizures. Three main types of propagated focal seizures observed in recent intracortical microelectrode recordings in humans were modelled: seizures characterized by sustained (∼30−60 Hz) gamma local field potential (LFP) oscillations; seizures where the onset in the propagated site consisted of LFP spikes that later evolved into rhythmic (∼2−3 Hz) spike-wave complexes (SWCs); and seizures where a brief stage of low-amplitude fast-oscillation (∼10−20 Hz) LFPs preceded the SWC activity. Our findings are fourfold: (1) The interaction between elevated [K+]o (due to abnormal potassium buffering by glial cells) and the strength of synaptic inhibition plays a predominant role in shaping these three types of seizures. (2) Strengthening of inhibition leads to the onset of sustained narrowband gamma seizures. (3) Transition into SWC seizures is obtained either by the weakening of inhibitory synapses, or by a transient strengthening followed by an inhibitory breakdown (e.g. GABA depletion). This reduction or breakdown of inhibition among fast-spiking (FS) inhibitory interneurons increases their spiking activity and leads them eventually into depolarization block. Ictal spike-wave discharges in the model are then sustained solely by pyramidal neurons. (4) FS cell dynamics are also critical for seizures where the evolution into SWC activity is preceded by low-amplitude fast oscillations. Different levels of elevated [K+]o were important for transitions into and maintenance of sustained gamma oscillations and SWC discharges. Overall, our modelling study predicts that the interaction between inhibitory interneurons and [K+]o glial buffering under abnormal conditions may explain different types of ictal transitions and dynamics during propagated seizures in human focal epilepsy.