Biology subjects

Sirota, A.

Publications and source records attributed to Sirota, A..

6 recordsLinked to original sources

bioRxiv2024

Large-scale infra-slow dynamics of extracellular potentials linked to synchronous states revealed by graphene neural probes

Infra-slow (<0.5 Hz) brain dynamics reflect homeostatic and neuromodulatory processes that modulate neuronal excitability and shape faster oscillations across brain regions. Infra-slow brain activity is typically inferred from magnetic or optical imaging, but these methods are limited in temporal resolution and compatibility with unconstrained behavior. Infra-slow local field potentials (isLFPs) could provide a direct measure of infra-slow network dynamics, but have remained poorly characterized due to the absence of scalable, DC-coupled recording methods. Here, we introduce DC-coupled electrophysiological imaging based on arrays of up to 512 multiplexed graphene transistors enabling stable, high-density recordings across cortical regions and cortical layers in freely moving rats. We developed an analytical framework for the analysis of wide-band LFP, revealing that synchronous oscillatory states of variable duration and spatial scale are consistently linked to topographically and translaminarly structured DC potential shifts. We propose a physiological model linking these DC shifts to sustained gradients of extracellular K+ concentration, providing a mechanistic connection between neuronal synchrony and isLFP dynamics. By integrating DC-coupled sensing, multiplexed scalability, and depth-surface co-registration, this work establishes a new modality for imaging-like electrophysiology in freely moving animals and a framework for interpreting infra-slow dynamics.

neuroscience↗

bioRxiv2024

Anatomically resolved oscillatory bursts orchestrate visual thalamocortical activity during naturalistic stimulus viewing

Natural vision involves encoding of complex visual input, which engages a plethora of interacting circuit mechanisms. In the mammalian forebrain, one signature of such interacting circuit mechanisms is fast oscillatory dynamics, which can be reflected in the local field potential (LFP). We here used data from the Allen Neuropixels Visual Coding project to show that local visual features in naturalistic stimuli induce retinotopically specific V1 oscillations in various frequency bands. These LFP oscillations occurred in bursts, were localized to specific V1 layers, and were associated with phase coupling of V1 translaminar spiking, pointing to feature-specific circuit motifs. Finally, we discovered that these visually-induced circuit motifs occurred across a range of stimuli, suggesting that they might constitute general routes for feature-specific information flow. Together, our analyses demonstrate visually-induced, fast oscillations, which likely reflect the operation of distinct mesoscale circuits for the differential and multiplexed coding of complex visual input and feature-specific thalamo-cortical information propagation.

neuroscience↗

bioRxiv2020

Phasic oxygen dynamics underlies fast choline-sensitive biosensor signals in the brain of behaving rodents

Fast time-scale modulation of synaptic and cellular physiology by acetylcholine is critical for many cognitive functions, but direct local measurement of neuromodulator dynamics in freely-moving behaving animals is technically challenging. Recent in vivo brain measurements using choline oxidase (ChOx)-based electrochemical biosensors have reported surprising fast cholinergic transients associated with reward-related behavioral events. However, in vivo recordings with conventional ChOx biosensors could be biased by phasic local field potential and O2-evoked enzymatic responses. Here, we have developed a Tetrode-based Amperometric ChOx (TACO) sensor enabling minimally invasive artifact-free simultaneous measurement of cholinergic activity and O2. Strikingly, the TACO sensor revealed highly-correlated O2 and ChOx transients following spontaneous locomotion and sharp-wave/ripples fluctuations in the hippocampus of behaving rodents. Quantitative analysis of spontaneous activity, in vivo and in vitro exogenous O2 perturbations revealed a directional effect of O2 on ChOx phasic signals. Mathematical modeling of biosensors identified O2-evoked non-steady-state ChOx kinetics as a mechanism underlying artifactual biosensor phasic transients. This phasic O2-dependence of ChOx-based biosensor measurements confounds phasic cholinergic dynamics readout in vivo, challenging previously proposed ACh role in reward-related learning. The discovered mechanism and quantitative modeling is generalizable to any oxidase-based biosensor, entailing rigorous controls and new biosensor designs.

neuroscience↗

bioRxiv2019

Multi-shanks SiNAPS Active Pixel Sensor CMOSprobe: 1024 simultaneously recording channels for high-density intracortical brain mapping

The advent of implantable active dense CMOS neural probes opened a new era for electrophysiology in neuroscience. These single shank electrode arrays, and the emerging tailored analysis tools, provide for the first time to neuroscientists the neurotechnology means to spatiotemporally resolve the activity of hundreds of different single-neurons in multiple vertically aligned brain structures. However, while these unprecedented experimental capabilities to study columnar brain properties are a big leap forward in neuroscience, there is the need to spatially distribute electrodes also horizontally. Closely spacing and consistently placing in well-defined geometrical arrangement multiple isolated single-shank probes is methodologically and economically impractical. Here, we present the first high-density CMOS neural probe with multiple shanks integrating thousands of closely spaced and simultaneously recording microelectrodes to map neural activity across 2D lattice. Taking advantage from the high-modularity of our electrode-pixels-based SiNAPS technology, we realized a four shanks active dense probe with 256 electrode-pixels/shank and a pitch of 28 {micro}m, for a total of 1024 simultaneously recording channels. The achieved performances allow for full-band, whole-array read-outs at 25 kHz/channel, show a measured input referred noise in the action potential band (300-7000 Hz) of 6.5 {+/-} 2.1{micro}VRMS, and a power consumption <6 {micro}W/electrode-pixel. Preliminary recordings in awake behaving mice demonstrated the capability of multi-shanks SiNAPS probes to simultaneously record neural activity (both LFPs and spikes) from a brain area >6 mm2, spanning cortical, hippocampal and thalamic regions. High-density 2D array enables combining large population unit recording across distributed networks with precise intra- and interlaminar/nuclear mapping of the oscillatory dynamics. These results pave the way to a new generation of high-density and extremely compact multi-shanks CMOS-probes with tunable layouts for electrophysiological mapping of brain activity at the single-neurons resolution.

bioengineering↗

bioRxiv2018

Breathing coordinates limbic network dynamics underlying memory consolidation

The coordinated activity between remote brain regions underlies cognition and memory function. Although neuronal oscillations have been proposed as a mechanistic substrate for the coordination of information transfer and memory consolidation during sleep, little is known about the mechanisms that support the widespread synchronization of brain regions and the relationship of neuronal dynamics with other bodily rhythms, such as breathing. Here we address this question using large-scale recordings from a number of structures, including the medial prefrontal cortex, hippocampus, thalamus, amygdala and nucleus accumbens in mice. We identify a dual mechanism of respiratory entrainment, in the form of an intracerebral corollary discharge that acts jointly with an olfactory reafference to coordinate limbic network dynamics, such as hippocampal ripples and cortical UP and DOWN states, involved in memory consolidation. These results highlight breathing, a perennial rhythmic input to the brain, as an oscillatory scaffold for the functional coordination of the limbic circuit, enabling the segregation and integration of information flow across neuronal networks.

neuroscience↗

bioRxiv2017

Virtual Reality system for freely-moving rodents.

Spatial navigation, active sensing, and most cognitive functions rely on a tight link between motor output and sensory input. Virtual reality (VR) systems simulate the sensorimotor loop, allowing flexible manipulation of enriched sensory input. Conventional rodent VR systems provide 3D visual cues linked to restrained locomotion on a treadmill, leading to a mismatch between visual and most other sensory inputs, sensory-motor conflicts, as well as restricted naturalistic behavior. To rectify these limitations, we developed a VR system (ratCAVE) that provides realistic and low-latency visual feedback directly to head movements of completely unrestrained rodents. Immersed in this VR system, rats displayed naturalistic behavior by spontaneously interacting with and hugging virtual walls, exploring virtual objects, and avoiding virtual cliffs. We further illustrate the effect of ratCAVE-VR manipulation on hippocampal place fields. The newly-developed methodology enables a wide range of experiments involving flexible manipulation of visual feedback in freely-moving behaving animals.

animal behavior and cognition↗