Biology subjects

Marmelshtein, A.

Publications and source records attributed to Marmelshtein, A..

6 recordsLinked to original sources

bioRxiv2025

An early surge of norepinephrine along brainstem pathways drives sensory-evoked awakening

The locus coeruleus norepinephrine (LC-NE) system regulates arousal and awakening; however, it remains unclear whether the LC does this in a global or circuit specific manner. We hypothesized that sensory-evoked awakenings are predominantly regulated by specific LC-NE efferent pathways. Anatomical, physiological, and functional modularities of LC-NE pathways involving the mouse basal forebrain (BF) and pontine reticular nucleus (PRN) were tested. We found partial anatomical segregation between the LC->PRN and LC->BF circuits. Extracellular NE dynamics in BF and PRN exhibited distinct sound-evoked activation during sleep, including a fast sound-evoked NE peak specific to PRN. Causal optogenetic interrogation of LC efferent pathways, by retro-ChR2 activation or PdCO silencing of synapses in target regions, revealed a pivotal role for early LC->PRN activity in driving arousal and sound-evoked awakenings. Together, our results uncover a prominent role for early LC-NE PRN activity in connecting sensory and arousal pathways and establish LC heterogeneity in regulating arousal. O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=200 SRC="FIGDIR/small/635485v1_ufig1.gif" ALT="Figure 1"> View larger version (49K): org.highwire.dtl.DTLVardef@eb7b3eorg.highwire.dtl.DTLVardef@1e85006org.highwire.dtl.DTLVardef@ddfa7eorg.highwire.dtl.DTLVardef@1687606_HPS_FORMAT_FIGEXP M_FIG C_FIG

neuroscience↗

bioRxiv2024

Changes in responses of auditory cortex neurons upon falling asleep and awakening

The neural processes that change when falling asleep are only partially understood. At the cortical level, features of both spontaneous neural activity and sensory responses change between wakefulness and sleep. For example, in early auditory cortex, sleep increases the occurrence of post-onset silent (OFF) periods and elevates population synchrony. However, it remains unknown whether such changes occur abruptly or gradually around sleep onset and awakening. Here, we recorded spontaneous and sound-evoked neuronal spiking activity in early auditory cortex along with polysomnography during thousands of episodes when male rats fell asleep or woke up. We found that when falling asleep, stimulus-induced neuronal silent periods (OFF periods), characteristic of non-rapid eye movement (NREM) sleep, increased within few seconds around sleep onset. By contrast, a gradual increase in neuronal population synchrony built up over tens of seconds until reaching maximal levels. EEG auditory-evoked potentials likely representing stimulus-triggered "K complexes" changed along with post-onset neuronal firing, whereas ongoing EEG slow wave activity was associated with neuronal population synchrony. Similar effects, but with opposite direction, were observed around awakenings. The results highlight late stimulus-induced neuronal silence as a key feature changing abruptly around transitions between vigilance states, likely reflecting neuronal bistability and manifesting also in EEG evoked potentials. More generally, these findings emphasize the added value of going beyond monitoring ongoing activity and perturbing the nervous system to reveal its state - an insight that could also help guide development of more sensitive non-invasive monitors of falling asleep in humans.

neuroscience↗

bioRxiv2022

Sleep-like changes in neural processing emerge during sleep deprivation in early auditory cortex

Insufficient sleep is commonplace in modern lifestyle and can lead to grave outcomes, yet the changes in neuronal activity accumulating over hours of extended wakefulness remain poorly understood. Specifically, which aspects of cortical processing are affected by sleep deprivation (SD), and whether they also affect early sensory regions, remains unclear. Here, we recorded spiking activity in rat auditory cortex along with polysomnography while presenting sounds during SD followed by recovery sleep. We found that frequency tuning, onset responses, and spontaneous firing rates were largely unaffected by SD. By contrast, SD decreased entrainment to rapid ([≥]20 Hz) click-trains, increased population synchrony, and increased the prevalence of sleep-like stimulus-induced silent periods, even when ongoing activity was similar. Recovery NREM sleep was associated with similar effects as SD with even greater magnitude, while auditory processing during REM sleep was similar to vigilant wakefulness. Our results show that processes akin to those in NREM sleep invade the activity of cortical circuits during SD, already in early sensory cortex.

neuroscience↗

bioRxiv2021

Impaired top-down auditory processing despite extensive single-neuron responses during human sleep

Sleep in all species is universally defined as a reversible, homeostatically-regulated state of a reduced behavioral responsiveness, with a high arousal threshold in response to external sensory stimulation1. However, it remains unclear whether sleep mainly gates motor output or affects responses along sensory pathways, and whether sleep primarily modulates specific aspects of the sensory response such as feedforward vs. feedback signaling2-7. Here, we simultaneously recorded polysomnography, iEEG, microwire LFPs, and neuronal spiking activity during wakefulness and sleep in 13 epilepsy patients implanted with clinical depth electrodes, while presenting auditory stimuli (e.g. click-trains, words, music). The results revealed robust spiking and induced LFP high-gamma (80-200Hz) power responses during both NREM and REM sleep across the lateral temporal lobe. The magnitude of the responses was only moderately attenuated in sleep, most notably for late responses beyond the early auditory cortex. Nonetheless, sleep responses maintained their tight locking with soundwave envelopes and their information content was only minimally affected. In contrast, a decrease in LFP alpha-beta (10-30Hz) power responses was prevalent in wakefulness but significantly disrupted in sleep. Entrainment to 40 Hz click-trains was comparable across REM sleep and wakefulness, but reduced in NREM sleep. In conclusion, our results establish the presence of extensive and robust auditory responses during sleep while LFP alpha-beta power decrease, likely reflecting top-down processes8-10, is deficient. More broadly, our findings suggest that feedback signalling is key to conscious sensory processing11-13.

neuroscience↗

bioRxiv2020

Anesthetic Drug Concentration Rather Than Abrupt Behavioral Unresponsiveness Linearly Degrades Responses in the Rat Primary Auditory Cortex

Despite extensive knowledge of its molecular and cellular effects, how anesthesia affects sensory processing remains poorly understood. In particular, it remains unclear whether anesthesia modestly or robustly degrades activity in primary sensory regions, and whether such changes are linked to anesthesia drug concentration vs. behavioral unresponsiveness, since these are typically confounded. Here, we employed slow gradual intravenous propofol anesthesia induction together with auditory stimulation and intermittent assessment of behavioral responsiveness while recording epidural EEG, and neuronal spiking activity in the primary auditory cortex (PAC) of eight rats. We found that all main components of neuronal activity including spontaneous firing rates, onset response magnitudes, onset response latencies, post-onset neuronal silence duration, and late-locking to 40Hz click-trains, gradually deteriorated in a dose- dependent manner with increasing anesthesia levels without showing abrupt changes around loss of righting reflex or other time-points. Thus, the dominant factor affecting PAC responses is the anesthesia drug concentration rather than any sudden, dichotomous behavioral state changes. Our findings explain a wide array of seemingly conflicting results in the literature that, depending on the precise definition of wakefulness (vigilant vs. drowsy) and anesthesia (light vs. deep/surgical), report a spectrum of effects in primary regions ranging from minimal to dramatic differences.

neuroscience↗

bioRxiv2018

Anesthesia-induced loss of consciousness disrupts auditory responses beyond primary cortex

Despite its ubiquitous use in medicine, and extensive knowledge of its molecular and cellular effects, how anesthesia induces loss of consciousness (LOC) and affects sensory processing remains poorly understood. Specifically, it is unclear whether anesthesia primarily disrupts thalamocortical relay or intercortical signaling. Here we recorded intracranial EEG (iEEG), local field potentials (LFPs), and single-unit activity in patients during wakefulness and light anesthesia. Propofol infusion was gradually increased while auditory stimuli were presented and patients responded to a target stimulus until they became unresponsive. We found widespread iEEG responses in association cortices during wakefulness, which were attenuated and restricted to auditory regions upon LOC. Neuronal spiking and LFP responses in primary auditory cortex (PAC) persisted after LOC, while responses in higher-order auditory regions were variable, with neuronal spiking largely attenuated. Gamma power induced by word stimuli increased after LOC while its frequency profile slowed, thus differing from local spiking activity. In summary, anesthesia-induced LOC disrupts auditory processing in association cortices while relatively sparing responses in PAC, opening new avenues for future research into mechanisms of LOC and the design of anesthetic monitoring devices.

neuroscience↗