Detection of neuronal OFF periods as low amplitude neural activity segments

Abstract

Background During non-rapid eye movement sleep (NREM), alternating periods of synchronised high (ON period) and low (OFF period) neuronal activity are associated with high amplitude delta band (0.5–4 Hz) oscillations in neocortical electrophysiological signals termed slow waves. As this oscillation is dependent crucially on hyperpolarisation of cortical cells, there is an interest in understanding how neuronal silencing during OFF periods leads to the generation of slow waves and whether this relationship changes between cortical layers. A formal, widely adopted definition of OFF periods is absent, complicating their detection. Here, we grouped segments of high frequency neural activity containing spikes, recorded as multiunit activity from the neocortex of freely behaving mice, on the basis of amplitude and asked whether the population of low amplitude (LA) segments displayed the expected characteristics of OFF periods. Results Average LA segment length was comparable to previous reports for OFF periods but varied considerably, from as short as 8 ms to > 1 s. LA segments were longer and occurred more frequently in NREM but shorter LA segments also occurred in half of rapid eye movement sleep (REM) epochs and occasionally during wakefulness. LA segments in all states were associated with a local field potential (LFP) slow wave that increased in amplitude with LA segment duration. We found that LA segments > 50 ms displayed a homeostatic rebound in incidence following sleep deprivation whereas short LA segments (< 50 ms) did not. The temporal organisation of LA segments was more coherent between channels located at a similar cortical depth. Conclusion We corroborate previous studies showing neural activity signals contain uniquely identifiable periods of low amplitude with distinct characteristics from the surrounding signal known as OFF periods and attribute the new characteristics of vigilance-state-dependent duration and duration-dependent homeostatic response to this phenomenon. This suggests that ON/OFF periods are currently underdefined and that their appearance is less binary than previously considered, instead representing a continuum.

Deficient synaptic neurotransmission results in a persistent sleep-like cortical activity across vigilance states in mice

“…These EEG and LFP results raised the following question: what is it in the brain activity of rlss mice that is different for such sleep-architecture and spectral variations to arise? Using MUA recordings and our recently developed 'OFF-period' detection algorithm (Harding et al, 2023), we discovered that neuronal firing in rlss mice ceases for seconds at a time during NREMS, in a locally synchronised manner (Figure 2a and Movie 1). Compared to WTs, in rlss animals, periods of such synchronised neuronal silence ('OFF-periods') lasted significantly longer and coincided with very low-amplitude, nearly isoelectric EEG and LFP traces (Figure 2a,b and Movie 1).…”

“…Local field potentials (LFP) and multi-unit activity (MUA) instead allow us to look at sleepwake dynamics at a more local level. In addition, as the initiation of slow-waves (depth positive/surface negative deflections) correspond to periods of neuronal silence (Calvet et al, 1973;Contreras and Steriade, 1995;Harding et al, 2023;Mukovski et al, 2007;Steriade et al, 1993;Steriade et al, 2001;Vyazovskiy et al, 2009), which also depend on the levels of network synchrony (Vyazovskiy et al, 2009), multi-unit activity allows us to investigate the underlying patterns of neuronal silence ('OFF-periods') (Harding et al, 2023).…”