RESUMEN
KEY POINTS: 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. We provide a simple analytical template that captures the firing response of both pyramidal neurons and various theoretical models. 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. 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.
Asunto(s)
Modelos Neurológicos , Células Piramidales/fisiología , Corteza Visual/fisiología , Animales , Femenino , Técnicas In Vitro , Masculino , Potenciales de la Membrana , Ratones , Técnicas de Placa-Clamp , Canales de Sodio/fisiologíaRESUMEN
OBJECTIVE: Scalp-derived human somatosensory evoked potentials (SEPs) contain high-frequency oscillations (600 Hz; 'sigma-burst') reflecting concomitant bursts of spike responses in primary somatosensory cortex that repeat regularly at 600 Hz. Notably, recent human intracranial SEP have revealed also 1 kHz responses ('kappa-burst'), possibly reflecting non-rhythmic spiking summed over multiple cells (MUA: multi-unit activity). However, the non-invasive detection of EEG signals at 1 kHz typical for spikes has always been limited by noise contributions from both, amplifier and body/electrode interface. Accordingly, we developed a low-noise recording set-up optimised to map non-invasively 1 kHz SEP components. METHODS: SEP were recorded upon 4 Hz left median nerve stimulation in 6 healthy human subjects. Scalp potentials were acquired inside an electrically and magnetically shielded room using low-noise custom-made amplifiers. Furthermore, in order to reduce thermal Johnson noise contributions from the sensor/skin interface, electrode impedances were adjusted to ≤ 1 kΩ. Responses averaged after repeated presentation of the stimulus (n=4000 trials) were evaluated by spatio-temporal pattern analyses in complementary spectral bands. RESULTS: Three distinct spectral components were identified: N20 (<100 Hz), sigma-burst (450-750 Hz), and kappa-burst (850-1200 Hz). The two high-frequency bursts (sigma, kappa) exhibited distinct and partially independent spatiotemporal evolutions, indicating subcortical as well as several cortical generators. CONCLUSIONS: Using a dedicated low-noise set-up, human SEP 'kappa-bursts' at 1 kHz can be non-invasively detected and their scalp distribution be mapped. Their topographies indicate a set of subcortical/cortical generators, at least partially distinct from the topography of the 600 Hz sigma-bursts described previously. SIGNIFICANCE: The non-invasive detection and surface mapping of 1 kHz EEG signals presented here provides an essential step towards non-invasive monitoring of multi-unit spike activity.