Ultrafast (400 Hz) network oscillations induced in mouse barrel cortex 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 important, if not fully understood cognitive functions. Oscillations at different frequency bands are hallmarks of specific brain and behavioral states. At the higher end of the spectrum, ultrafast (400-600 Hz) oscillations in the somatosensory cortex, in response to peripheral nerve stimulation or punctate sensory stimuli, were previously observed in humans and in 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, in brain slices from mouse somatosensory (barrel) cortex, elicited in the thalamorecipient layer local field potential (LFP) oscillations which we dubbed 'ripplets', consisting of a sequence of precisely reproducible 2-5 negative transients at ~400 Hz which originated in the postsynaptic cortical network. Fast-spiking (FS) inhibitory interneurons fired ~400 Hz spike bursts entrained to the LFP oscillation, while regular-spiking (RS) excitatory neurons typically fired only 1-2 spikes per ripplet, preceding FS spikes by ~1.5 ms. Spike bursts were exquisitely synchronized between neighboring FS cells, while RS cells received synchronous, precisely repeating sequences of alternating excitatory and inhibitory postsynaptic currents (E/IPSCs) phase-locked to the LFP oscillation. Spikes in FS cells followed at short (~0.4 ms) latency onset of EPSCs and preceded (by ~0.8 ms) onset of IPSCs in simultaneously recorded RS cells, suggesting that FS cells were driven to fire by phasic inputs from excitatory cells, and in turn evoked volleys of inhibition which enforced synchrony on excitatory cells. We suggest that ripplets are an intrinsically generated cortical response to a strong, synchronous thalamocortical volley. Ripplets and the associated spike sequences in excitatory cells could provide increased bandwidth for encoding and transmitting sensory information. In addition, optogenetically induced ripplets are a uniquely accessible model system for studying synaptic mechanisms of fast and ultrafast cortical and hippocampal 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.…”

Exploring sensory, motor, and pain responses as potential side or therapeutic effects of sub-2 mA, 400 Hz transcranial pulsed current stimulation

“…Although currently limited to Singapore, the introduction of the AscenZ-IV Stimulator marks a significant advancement in patient-centric healthcare. The decision to utilize 400 Hz tPCS draws inspiration from theoretical models proposing the role of high-frequency brain activities in signal transmission and the identification of cortical circuits in the primary motor cortex [6][7][8]. Furthermore, 400 Hz stimulation has demonstrated the ability to enhance the detection of rapid changes in ultra-fast EEG activity (60-1000 Hz).…”