Balance of excitation and inhibition is a fundamental feature of in vivo network activity and is important for its computations. However, its presence in the neocortex of higher mammals is not well established. We investigated the dynamics of excitation and inhibition using dense multielectrode recordings in humans and monkeys. We found that in all states of the wake-sleep cycle, excitatory and inhibitory ensembles are well balanced, and co-fluctuate with slight instantaneous deviations from perfect balance, mostly in slow-wave sleep. Remarkably, these correlated fluctuations are seen for many different temporal scales. The similarity of these computational features with a network model of self-generated balanced states suggests that such balanced activity is essentially generated by recurrent activity in the local network and is not due to external inputs. Finally, we find that this balance breaks down during seizures, where the temporal correlation of excitatory and inhibitory populations is disrupted. These results show that balanced activity is a feature of normal brain activity, and break down of the balance could be an important factor to define pathological states.

Key pointsr We recreated in vitro the fluctuation-driven regime observed at the soma during asynchronous network activity in vivo and we studied the firing rate response as a function of the properties of the membrane potential fluctuations.r We provide a simple analytical template that captures the firing response of both pyramidal neurons and various theoretical models.r We found a strong heterogeneity in the firing rate response of layer V pyramidal neurons: in particular, individual neurons differ not only in their mean excitability level, but also in their sensitivity to fluctuations.r Theoretical modelling suggest that this observed heterogeneity might arise from various expression levels of the following biophysical properties: sodium inactivation, density of sodium channels and spike frequency adaptation.Abstract Characterizing the input-output properties of neocortical neurons is of crucial importance for understanding the properties emerging at the network level. In the regime of low-rate irregular firing (such as in the awake state), determining those properties for neocortical cells remains, however, both experimentally and theoretically challenging. Here, we studied this problem using a combination of theoretical modelling and in vitro experiments. We first identified, theoretically, three somatic variables that describe the dynamical state at the soma in this fluctuation-driven regime: the mean, standard deviation and time constant of the membrane potential fluctuations. Next, we characterized the firing rate response of individual layer V pyramidal cells in this three-dimensional space by means of perforated-patch recordings and dynamic clamp in the visual cortex of juvenile mice in vitro. We found that individual neurons strongly differ not only in terms of their excitability, but also, and unexpectedly, in their sensitivities to fluctuations. Finally, using theoretical modelling, we attempted to reproduce these results. The model predicts that heterogeneous levels of biophysical properties such as sodium inactivation, sharpness of sodium activation and spike frequency adaptation account for the observed diversity of firing rate responses. Because the firing rate response will determine population rate dynamics during asynchronous neocortical activity, our results show that cortical populations are functionally strongly inhomogeneous in young mouse visual cortex, which should have important consequences on the strategies of cortical computation at early stages of sensory processing. Abbreviations EIF, exponential integrate-and-fire model; iLIF, inactivating leaky integrate-and-fire; LIF, leaky integrate and fire model; sfaLIF, LIF model with spike-frequency adaptation only.

Beta (β)-and gamma (γ)-oscillations are present in different cortical areas and are thought to be inhibition-driven, but it is not known if these properties also apply to γ-oscillations in humans. Here, we analyze such oscillations in high-density microelectrode array recordings in human and monkey during the wake-sleep cycle. In these recordings, units were classified as excitatory and inhibitory cells. We find that γ-oscillations in human and β-oscillations in monkey are characterized by a strong implication of inhibitory neurons, both in terms of their firing rate and their phasic firing with the oscillation cycle. The β-and γ-waves systematically propagate across the array, with similar velocities, during both wake and sleep. However, only in slow-wave sleep (SWS) β-and γ-oscillations are associated with highly coherent and functional interactions across several millimeters of the neocortex. This interaction is specifically pronounced between inhibitory cells. These results suggest that inhibitory cells are dominantly involved in the genesis of β-and γ-oscillations, as well as in the organization of their large-scale coherence in the awake and sleeping brain. The highest oscillation coherence found during SWS suggests that fast oscillations implement a highly coherent reactivation of wake patterns that may support memory consolidation during SWS.excitation | inhibition | state-dependent firing | wave propagation | synchrony N eocortical beta (β)-and gamma (γ)-oscillations have been largely studied in the context of action/cognition during wakefulness (1-3). Although numerous studies have focused intensely on the information-processing role of β and γ during wakefulness, these rhythms do also occur during deep anesthesia and natural sleep (4-6). Additionally, although very-high-frequency allocortical oscillations (e.g., ripples at 80-200 Hz and fast ripples at 200-500 Hz in rodent/human hippocampus) have been thoroughly implicated in sleep-dependent memory consolidation (ref. 7 and reviewed in refs. 8 and 9), the occurrence and role of neocortical β-and γ-oscillations during sleep remain largely unexplored and related studies have been limited to macroscopic (whole-brain) scales (e.g., ref. 10). A recent study using microwires and intracranial electroencephalography (iEEG) recordings in the neocortex of epileptics has verified the strong presence of γ-oscillations during slow-wave sleep (SWS) (11). That study also showed a marked increase of spiking during γ, a suggestive indicator of association with cortical UP states. Here, we evaluate the presence of neocortical β-and γ-oscillations during the wake-sleep cycle at the level of local circuitry using dense 2D multielectrode recordings with identified excitatory and inhibitory cells (12, 13).Experimental and theoretical studies suggest that thalamocortical oscillations (including β and γ) are generated through a combination of intrinsic mechanisms involving the interplay between different ionic currents and extrinsic interaction of inhibitory and excitatory c...