Ultrafast (>400 Hz) network oscillations induced in thalamorecipient cortical layers by optogenetic activation of thalamocortical axons

Abstract

Oscillations of extracellular voltage, reflecting synchronous rhythmic activity in large populations of neurons, are a ubiquitous feature in the mammalian brain and are thought to subserve critical, if not fully understood cognitive functions. Oscillations at different frequency bands are hallmarks of specific brain or behavioral states. At the higher end of the scale, ultrafast (400-600 Hz) oscillations in the somatosensory cortex, in response to peripheral stimulation, were observed in human and a handful of animal studies; however, their synaptic basis and functional significance remain largely unexplored. Here we report that brief optogenetic activation of thalamocortical axons ex-vivo elicited precisely reproducible, ~410 Hz local field potential wavelets ("ripplets") in middle layers of mouse somatosensory (barrel) cortex. Fast-spiking (FS) inhibitory interneurons were exquisitely synchronized with each other and fired spike bursts in anti-phase with ripplets, while excitatory neurons fired only 1-2 spikes per stimulus. Both subtypes received shared excitatory inputs at ripplet frequency, and bursts in layer 5 FS cells required intact connection with layer 4, suggesting that layer 4 excitatory cells were driving FS bursts in both layers. Ripplets may be a ubiquitous cortical response to exceptionally salient sensory stimuli, and could provide increased bandwidth for encoding and transmitting sensory information. Lastly, optogenetically-induced ripplets are a uniquely accessible model system for studying synaptic mechanisms of fast and ultrafast oscillations.

Single closed‐loop acoustic stimulation targeting memory consolidation suppressed hippocampal ripple and thalamo‐cortical spindle activity in mice

“…Acoustic stimuli evoke not only brainstem but also hippocampal responses within 50 ms post‐stimulation (Brankack & Buzsáki, 1986). Thus, we presume that strong depolarizing input of the acoustic stimulus, impacting the hippocampus in a state prone to generate ripples, can facilitate pyramidal cell‐interneuron interactions producing increased ripple activity (Hu et al, 2023; Stark et al, 2014). The finding that cortical activity in the ripple range (Figure 3) is of lower magnitude than hippocampal ripples indicates that the transient increase in hippocampal ripples occurring shortly after onset of the acoustic stimulation is a direct physiological response to stimulation.…”

Excitability modulations of somatosensory perception do not depend on feedforward neuronal population spikes

“…The principal aim of the current study was to test whether high-frequency oscillations (HFO), interpreted as a measure of population spiking activity (Baker et al, 2003;Curio, 2000;Waterstraat et al, 2021;Hu et al, 2023;Shimazu et al, 2000;Ozaki & Hashimoto, 2011), respond to the physical intensity of the presented stimulus as well as encode fluctuations of the subjectively perceived stimulus intensity. Previous studies, based on local field potentials, extracellular single unit recordings and surface EEG in non-human animals concluded that it is very likely that the intracortical component of HFO originate from the same pyramidal cells as the N20 potential (Shimazu et al, 2000;Ikeda et al, 2005;Baker et al, 2003).…”

“…Following the notion that HFO are generated at basal regions of cortical pyramidal cells (Baker et al, 2003;Curio, 2000;Shimazu et al, 2000;Hu et al, 2023) while the N20 component reflects postsynaptic membrane potentials that propagate back along the apical dendrites towards superficial layers (Wikström et al, 1996;Bruyns-Haylett et al, 2017;Thorpe et al, 2024), the lack of behaviorally relevant HFO fluctuations in the current study in combination with the effects of N20 and alpha band amplitudes in our previous study (Stephani et al, 2021) suggests that moment-to-moment changes of the perceived stimulus intensity are mediated by top-down modulations in apical rather than basal dendritic compartments. This is not only well in line with Dendritic Integration Theory (Bachmann et al, 2020;Aru et al, 2020;Larkum, 2022) but also complies with recent observations of alpha band activity exerting a top-down influence on superficial layers of primary sensory regions (Halgren et al, 2019), as well as with earlier conceptions of the interplay between re-entrant bottom-up and top-down signals in superficial layers at early stages of the somatosensory response cascade (Cauller, 1995;Cauller & Kulics, 1991).…”

“…While HFO before the peak of the N20 may reflect thalamo-cortical spiking, HFO of purely cortical origin in BA 3b can be identified based on their tangential dipole topography (Gobbelé et al, 2004) and their onset at or just after the N20 peak (Baker et al, 2003;Ritter et al, 2008). It has been shown that the cortical HFO in BA 3b originate from very similar sources as the N20 (Ikeda et al, 2005;Shimazu et al, 2000), engage in initial cortical processing of naturalistic tactile information like the N20 (Baker et al, 2003), but reflect a physiologically different process than the N20 on a cellular level, that is, the interplay of incoming and outgoing action potentials of the involved pyramidal cells (likely in a fast exchange with neighboring interneurons in cortex layer 4; Hu et al, 2023;Ozaki & Hashimoto, 2011). Thus, in the context of our question, HFO allow to test whether the excitability modulations we observed in our previous study (Stephani et al, 2021) are manifested in neuronal population spikes that occur around the basal compartments of S1 pyramidal cells (middle layers) or rather unfold in post-synaptic membrane potentials -as reflected by the N20 potential -that propagate from the soma "back" towards the apical dendrites (superficial layers).…”