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.
Figure 1- Source Data 1 contains the cell count data used for Figure 1 - Figure Supplement 1;Figure 2- Source Data 1 contains the electrophysiological parameters data used for Figure 2 - Figure Supplement 1;Code used to calculate synchrony indices has been deposited to GitHub.
- Ariel Agmon
- Rachel E Hostetler
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Animal experimentation: Animals used in this study were housed at the AAALAC-accredited WVU Lab Animal Research Facility according to institutional, federal and AAALAC guidelines. Animal use followed the Public Health Service Policy on Humane Care and Use of Laboratory Animals, and was approved by the WVU Institutional Animal Care and Use Committee (protocol #1604002316). West Virginia University has a PHS-approved Animal Welfare Assurance D16-00362 (A3597-01).
- Eunji Cheong, Yonsei University, Republic of Korea
© 2023, Hu et al.
This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.
Blindness affects millions of people around the world. A promising solution to restoring a form of vision for some individuals are cortical visual prostheses, which bypass part of the impaired visual pathway by converting camera input to electrical stimulation of the visual system. The artificially induced visual percept (a pattern of localized light flashes, or ‘phosphenes’) has limited resolution, and a great portion of the field’s research is devoted to optimizing the efficacy, efficiency, and practical usefulness of the encoding of visual information. A commonly exploited method is non-invasive functional evaluation in sighted subjects or with computational models by using simulated prosthetic vision (SPV) pipelines. An important challenge in this approach is to balance enhanced perceptual realism, biologically plausibility, and real-time performance in the simulation of cortical prosthetic vision. We present a biologically plausible, PyTorch-based phosphene simulator that can run in real-time and uses differentiable operations to allow for gradient-based computational optimization of phosphene encoding models. The simulator integrates a wide range of clinical results with neurophysiological evidence in humans and non-human primates. The pipeline includes a model of the retinotopic organization and cortical magnification of the visual cortex. Moreover, the quantitative effects of stimulation parameters and temporal dynamics on phosphene characteristics are incorporated. Our results demonstrate the simulator’s suitability for both computational applications such as end-to-end deep learning-based prosthetic vision optimization as well as behavioral experiments. The modular and open-source software provides a flexible simulation framework for computational, clinical, and behavioral neuroscientists working on visual neuroprosthetics.
Extinction is a specific example of learning where a previously reinforced stimulus or response is no longer reinforced, and the previously learned behaviour is no longer necessary and must be modified. Current theories suggest extinction is not the erasure of the original learning but involves new learning that acts to suppress the original behaviour. Evidence for this can be found when the original behaviour recovers following the passage of time (spontaneous recovery) or reintroduction of the reinforcement (i.e. reinstatement). Recent studies have shown that pharmacological manipulation of noradrenaline (NA) or its receptors can influence appetitive extinction; however, the role and source of endogenous NA in these effects are unknown. Here, we examined the role of the locus coeruleus (LC) in appetitive extinction. Specifically, we tested whether optogenetic stimulation of LC neurons during extinction of a food-seeking behaviour would enhance extinction evidenced by reduced spontaneous recovery in future tests. LC stimulation during extinction trials did not change the rate of extinction but did serve to reduce subsequent spontaneous recovery, suggesting that stimulation of the LC can augment reward-related extinction. Optogenetic inhibition of the LC during extinction trials reduced responding during the trials where it was applied, but no long-lasting changes in the retention of extinction were observed. Since not all LC cells expressed halorhodopsin, it is possible that more complete LC inhibition or pathway-specific targeting would be more effective at suppressing extinction learning. These results provide further insight into the neural basis of appetitive extinction, and in particular the role of the LC. A deeper understanding of the physiological bases of extinction can aid development of more effective extinction-based therapies.