Single Unit publications

The neural representations of acoustic features that differ in the location or timbre of the emitter elicit similar perceptions, suggesting the existence of a robust stimulus‐response function between complex sounds and the activity of neural populations at all stages of the auditory system. This hypothesis is tested by decoding a random sound stream, using spike trains from a biophysical model of the auditory nerve and from large‐scale recordings in the inferior colliculus, the auditory thalamus, and the auditory cortex of awake mice. At the level of individual neurons, the reliability of temporal and rate codes is found to decrease along the ascending auditory pathways. Rate coding is progressively favored with increasing independence of neuron frequency tuning. Firing in the auditory cortex is found to be synergistic, whereas that in subcortical areas is more redundant. Finally, combinatorial codes involving neural firing and neural silence within neuron pairs are shown to efficiently encode sound information, particularly in the auditory cortex. Overall, these findings reveal a progressive transformation of the neural code from an individual, redundant, and temporal code at the periphery to a more distributed rate‐based code in the auditory cortex.

Aging disrupts brain network integration and is a significant risk factor for cognitive decline and neurological diseases, yet the circuit-level mechanisms underlying these changes remain unclear. Most previous studies have utilized cross-sectional or acute approaches, limiting insights into the longitudinal dynamics of the neural network. In this study, we chronically recorded laminar electrophysiological activity in both the primary visual cortex (V1) and hippocampal CA1 region of young (2-month-old) and aged (13-month-old) mice over 16 weeks. This approach allowed us to directly assess how aging modulates functional connectivity within hierarchically connected cortical and hippocampal circuits. We found that single-unit spiking activity and the signal-to-noise ratio were largely preserved in aged versus young mice, suggesting intact neuronal firing properties. However, aged mice showed global reductions in local field potential (LFP) power and a selective decrease in coherence across delta, alpha-beta, and gamma frequency bands within and between cortical layers and V1-CA1 pathways, while phase amplitude coupling remained unaffected. Interestingly, population level excitatory activity in CA1 was increased in aged animals. These findings indicate that aging selectively impairs network-level synchrony and temporal coordination in specific frequency bands and regions, with minimal loss of single-neuron function. Our results highlight the necessity of longitudinal, multi-region measurements to uncover the multi-scale vulnerabilities of the aging brain. Understanding the depth- and region-dependent circuit changes will guide strategies to preserve cortical-hippocampal communication and cognitive function in aging, as well as enhance neural interface technologies for older populations. NEW & NOTEWORTHY Aging non-uniformly degrades cortico-hippocampal networks, leading to region- and frequency-specific breakdowns in coordinated activity. While single-neuron activity remains preserved, disruptions in frequency-selective synchrony (delta and alpha-beta) were observed in aged mice, indicating impaired V1-CA1 communication as a marker of aging rather than neuronal degeneration. By separating single-neuron activity and large-scale dynamics, we reveal that aging alters communication between sensory and memory systems, underscoring the need for longitudinal approaches to capture age-related impairments in laminar connectivity.

How the brain organizes discrete actions into fluid sequences is a central problem in motor neuroscience. Competing models of basal ganglia (BG) function propose that BG neurons either signal sequence boundaries or encode movements across ordinal positions. Prior studies have largely examined fixed sequences with end-of-sequence rewards, leaving open whether such findings generalize to more naturalistic conditions. We trained four rhesus macaques to perform a visuomotor sequence task requiring four or five out-and-back joystick movements to peripheral targets. Sequences were completed under two conditions: a random condition, in which target order varied across trials, and a fixed condition, in which order was predictable and consistent. Rewards were delivered after each movement, dissociating reward timing from sequence completion. We recorded single-unit activity in arm-related regions of the globus pallidus (GP; n = 458) and primary motor cortex (M1; n = 306). Regression analyses revealed that many neurons in both GP and M1 encoded ordinal position within a sequence. Order effects were more frequent in the fixed condition, but were also present during random sequences. We found no evidence for preferential encoding of sequence initiation or termination in overlearned sequences, in contrast to prior studies reporting start/stop signals in basal ganglia. Weak effects appeared under the random condition in one animal pair, but these did not generalize across animals or conditions. Instead, neurons exhibited heterogeneous order-related responses spanning the full sequence. These results demonstrate that GP neurons, like those in M1, encode ordinal position throughout a sequence rather than acting solely as sequence initiators or terminators. This challenges boundary-specific models of BG function and highlights the BG’s broader role in representing serial order during motor sequence production.

Brain-computer interfaces (BCIs) enable direct communication between the brain and computers. However, their long-term functionality remains limited due to signal degradation caused by acute insertion trauma, chronic foreign body reaction (FBR), and biofouling at the device-tissue interface. To address these challenges, we introduce a multifunctional surface modification strategy called targeting-specific interaction and blocking nonspecific adhesion (TAB) coating for flexible fiber, achieving a synergistic integration of mechanical compliance and biochemical stability. The coating combines brain-derived neurotrophic factor (BDNF) conjugation and a lubricant-infused surface. This dual-functional design enables selective interaction with neurons and astrocytes while preventing nonspecific adhesion. Notably, high-quality single-unit neural signals were stably recorded for more than 12 months after implantation, demonstrating exceptional long-term recording performance. Integrating mechanical compatibility, antifouling properties, and selective neural cell interaction, the TAB-coated multifunctional fiber represents a transformative approach for neural implants, bridging biological systems with computational systems.

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-channelrhodopsin (ChR2) activation or Platynereis dumerilii ciliary opsin (PdCO) silencing of synapses in target regions, revealed a role for early LC → PRN activity in driving arousal and sound-evoked awakenings. Together, our results uncover a role for early LC-NE PRN activity in connecting sensory and arousal pathways and establish LC heterogeneity in regulating arousal.

Layer 6 corticothalamic (L6CT) neurons project to both cortex and thalamus, inducing multiple effects including the modulation of cortical and thalamic firing, and the emergence of high gamma oscillations in the cortical local field potential (LFP). We hypothesize that the high gamma oscillations driven by L6CT neuron activation reflect the dynamic engagement of intracortical and cortico-thalamo-cortical circuits. To test this, we optogenetically activated L6CT neurons in NTSR1-cre mice (both male and female) expressing channelrhodopsin-2 in L6CT neurons. Leveraging the vibrissal pathway in awake, head-fixed mice, we presented ramp-and-hold light at different intensities while recording neural activity in the primary somatosensory barrel cortex (S1) and the ventral posteromedial nucleus (VPm) of the thalamus using silicon probes. We found that the activation of S1 L6CT neurons induces high-frequency LFP oscillations in S1 that are modulated in frequency, but not in amplitude, across light intensities and over time. To identify which neuronal classes contribute to these oscillations, we examined the temporal evolution of firing rate in S1 and VPm. While most S1 neurons were steadily suppressed, VPm and S1 layer 4 fast spiking (L4 FS) neurons evolved from being suppressed to facilitated within 500 ms, suggesting differential recruitment of the intracortical versus cortico-thalamo-cortical pathways. Finally, we found that LFP frequency selectively correlates with VPm firing rate. Taken together, our data suggests that L6CT neurons sculpt the frequency of S1 LFP oscillations through cortico-thalamo-cortical circuits, linking the recurrent interactions mediated by L6CT neurons to the high gamma oscillations observed across physiological and pathological conditions.

Early sensory experience can exert lasting perceptual consequences. For example, a brief period of auditory deprivation early in life can lead to persistent spatial hearing deficits. Some forms of hearing loss (i.e., conductive; CHL) can distort acoustical cues needed for spatial hearing, which depend on inputs from both ears. We hypothesize that asymmetric acoustic input during development disrupts auditory circuits that integrate binaural information. Here, we identify prolonged maturation of the binaural auditory brainstem in the guinea pig by tracking auditory evoked potentials across development. Using this age range, we induce a reversible unilateral CHL and ask whether behavioral and neural maturation are disrupted. We find that developmental CHL is associated with alterations in a brainstem readout of binaural function, an effect that was not observed in a separate cohort with adult-onset CHL. Startle-based behavioral measures suggest that Early CHL animals exhibit reduced spatial resolution for high-frequency sound sources. Finally, single-unit recordings of auditory midbrain neurons reveal significantly poorer neural acuity to a sound location cue that largely depends on high-frequency sounds. Thus, these findings show that unilateral deprivation can disrupt developing auditory circuits that integrate binaural information and may give rise to lingering spatial hearing deficits.

Internal motive states, such as sexual arousal, drive behaviour in response to social cues. However, little is known about how internal states and external cues are integrated to release appropriate behaviours at the correct moment during a social interaction, such as the transition from the appetitive to the consummatory phases of mating 1,2 . Here we identify a neural circuit in male mice that gates the onset of consummatory reproductive behaviours on contact with a mating partner. Stimulating MPOA Esr1 ∩ Vgat hypothalamic neurons promotes mounting of conspecifics and three-dimensional dummy objects 3 . We find that such mounting depends on mechanosensory but not visual cues. Through a large-scale electrophysiological screen, we identify neurons in the subparafascicular thalamic nucleus that nonlinearly integrate medial preoptic area of the hypothalamus (MPOA) and mechanosensory input to encode contact with a potential mate. Circuit tracing and perturbations demonstrated that this conjunctive coding occurs by means of convergent disinhibition from MPOA and excitation from the spinal trigeminal nucleus. Functional manipulations and calcium recordings showed these social-contact neurons, marked by parathyroid hormone 2, were essential for and able to promote mounting. These data indicate that subparafascicular thalamic nucleus-parathyroid hormone 2 neurons integrate internal drive with social touch to trigger mounting at opportune moments during mating. More generally, our findings uncover a brain mechanism whereby an internal state can attribute a social quality to a generic touch to initiate purposeful reproductive actions.

The ability to recognize speakers by their voice despite acoustical variation plays a substantial role in primate social interactions. Although neurons in the macaque anterior temporal lobe (ATL) show invariance to face viewpoint, whether they also encode abstract representations of caller identity is not known. Here, we demonstrate that neurons in the voice-selective ATL of two macaques support invariant voice identity representations through dynamic population-level coding. These representations minimize neural distances across different vocalizations from the same individual while preserving distinct trajectories for different callers. This structure emerged from the coordinated activity of the broader neuronal ensemble, although a small subset of highly identity-selective neurons carried high identity information. Our findings provide a neural basis for voice identity recognition in primates and highlight the ATL as a key hub for integrating perceptual voice features into higher-level identity representations.

Purpose Present-day cochlear implants (CIs) can deliver usable speech reception in quiet surroundings. Most CI users, however, show impaired sensitivity to temporal fine structure, which hampers their use of pitch contours and spatial cues to segregate competing talkers. In previous short-term animal studies, we used intraneural (IN) electrodes to stimulate pathways originating from various cochlear turns. Neurons in the inferior colliculus synchronized to apical stimulation at higher rates than to stimulation of the middle-to-basal pathways that are stimulated primarily by today’s CIs. Here, we use non-invasive recordings to test the safety and efficacy of up to 6 months of IN implantation and stimulation in cats. Methods Deafened cats (ten female, two male) were implanted with IN and/or conventional CI electrodes. The IN electrodes were single activated-iridium shanks that targeted apical-turn fibers. Scalp recordings were made from sedated animals at 2–3-week intervals. Auditory brainstem responses to single electrical pulses (eABR) tracked sensitivity and growth of responses. Frequency following responses to electrical pulse trains (eFFR) assessed brainstem temporal transmission at varying pulse rates. Results Thresholds for eABR were lower for IN than for CI stimulation, dynamic ranges were wider, and (by inference) spread of activation was more restricted. The eFFR evaluated at latencies comparable to those of inferior-colliculus spikes synchronized at maximum pulse rates averaging > 360 pulses/s for IN compared to ~ 240 pulses/s for CI stimulation. The eABR thresholds and eFFR cutoff rates were stable out to 6 months after implantation. Conclusions The results demonstrate the safety and efficacy of chronic IN stimulation in an animal model. In a future clinical device, an IN electrode could augment cochlear-implant performance by enhancing temporal acuity, thereby improving speech reception amid competing sounds.

Migratory locusts ( Locusta migratoria ) emit two key odorants during aggregation: 4-vinylanisole (4VA), which serves as an aggregation pheromone attracting conspecifics to form swarms, and phenylacetonitrile (PAN), which acts as an aposematic signal and a precursor of a defense toxin, deterring conspecifics from cannibalism and protecting against predators. However, how locusts reconcile these two conflicting olfactory signals while aggregating is not yet understood. Our study addresses this by examining the release dynamics of the two signals, their behavioral effects, and the neural mechanisms underlying their perception. 4VA is released earlier and at lower locust densities than PAN, with PAN’s release increasing as aggregation progresses. Although PAN’s emission levels eventually exceed those of 4VA, locusts consistently exhibit a preference for the emitted blend, regardless of variations in proportions and concentrations. Notably, increasing amounts of 4VA added to PAN can counteract PAN’s repellent effects, but this is not the case when PAN is added to 4VA. Mechanistically, we found that antennal neurons responsive to 4VA suppress the activity of neurons responsive to PAN. In the antennal lobe, it is the conduction velocities of projection neurons, rather than other neural properties, that are responsible for the observed behavioral pattern, leading to an overall attractive response. Collectively, our findings imply that insects are capable of harmonizing the effects of two distinct pheromones to optimize both social cohesion and chemical defense.

Auditory perception can be modulated by other sensory stimuli. However, we do not fully understand the neural mechanisms that support multisensory behavior. Here, while male nonhuman primates detected a target vocalization that was embedded in a background chorus of vocalizations, we recorded spiking activity from the primary auditory cortex (A1). We found that a congruent video of a monkey eliciting the target vocalization improved the monkeys' behavior, relative to their performance when we only presented a static image of the monkey. As a proxy for the functional organization of A1, we compared the contribution of neurons with significant spectrotemporal response fields (STRFs) with those that had nonsignificant STRFs (nSTRFs). Because, on average, STRF and nSTRF neurons have different spike waveform shapes, firing rates, and neural-correlation structure, we hypothesized that they might belong to different neural populations. Consistent with this, we found that, although STRF neurons encode stimulus information through synchronized activity, task-related information in the primate A1 is encoded more as a structured dynamic process in the population of nSTRF neurons. Together, these findings suggest that modulatory multisensory behavior is supported by nSTRF neurons and identifies, for the first time, a functional differentiation between the role that STRF and nSTRF neurons contribute to behavior.

Diverse biological factors, such as sex and age, confer heterogeneity on sensory processing challenges in autism. These factors result in major difficulties in the processing of contextual information in social and non-social situations. To assess divergence in autistic traits, it is critical to consider sex- and age-related variability. Nevertheless, these differences remain largely elusive. Animal models of autism offer the possibility to examine contextual processing at the single-neuron level. Here, we investigated predictive processing of contextual auditory cues in the auditory midbrain of control and prenatally valproic acid-induced rats, a well-established animal model of autism. The rats were prepubertal and adult female and male animals. We performed single-unit recordings in the inferior colliculus of control and prenatally, or in utero , exposed rats under the classical oddball paradigm and non-repetitive cascade control sequences to study neuronal mismatch. This is the neuronal correlate of mismatch negativity, the brain’s automatic response to interruptions in environmental regularity. When comparing control and exposed rats, our results demonstrated a reduction in neuronal mismatch in rats exposed to valproic acid. However, exposed adult females exhibited an increased neuronal mismatch compared to their control counterparts. With respect to sex distinctions, valproic acid induced sex differences in neuronal mismatch of prepubertal and adult rats that are not observable in control animals. Moreover, we detected an age-dependent refinement in prediction error that is not affected by the drug. But valproic acid altered typical developmental trajectory of neuronal mismatch in both sexes. Such observations support sex- and age-related effects of in utero valproic acid exposure in contextual auditory processing at the neural level of the inferior colliculus. In autism, atypical predictive processing of environmental regularities underlies unusual responses to novel experiences. The present study highlights the importance of sex and age, that confer heterogeneity to these challenges.

Fragile X Syndrome (FXS) is a leading genetic cause of autism spectrum disorders (ASD)- associated behaviors, including sensory processing deficits. Sensory sensitivity and temporal processing deficits in the auditory domain will affect development of language and cognitive functions. The mouse model for FXS, Fmr1 KO, has shown remarkably similar auditory processing phenotypes to patients with FXS. In vitro cortical slice recordings show layer-specific differences in Fmr1 KO mouse local circuits, but it is unclear how these differences translate to changes in sensory processing. In this study, we used a depth multielectrode to record in vivo spikes and local field potentials across layers of the auditory cortex in Fmr1 KO and wildtype mice (WT), converting the latter to current source density (CSD) profiles for improved spatial resolution analysis. We observed reduced CSD sink amplitudes and inter-trial phase coherence, and an increase in trial-to-trial variability for temporally modulated stimuli in the KO mice. Results indicated a differential cortical layer pattern of activity in KO mice, with higher baseline gamma power in superficial and deep layers and higher resting delta and theta power in granular layers. Significantly elevated inter-trial variability was observed for CSD and spikes in KO mice. Auditory steady state responses to clicks or gaps at 40 Hz showed considerable trial-to-trial variability in a layer-specific manner in KO mice. Neural generators in the Fmr1 KO mouse auditory cortex failed to detect short gaps in noise, indicating severe temporal processing deficits. Altogether, this study indicates layer-specific cortical mechanisms of sensory hypersensitivity and temporal processing deficits in FXS.

The insular cortex is involved in a wide range of auditory functions in the mammalian brain. We studied the organization and basic response properties of auditory neurons in the insular cortex and adjacent areas by recording responses to sound stimuli in anesthetized female rats. Auditory neurons were present in an insulo-parietal auditory field that spans the boundary between the posterior insula, particularly in the granular insular cortex, and the ventral part of the adjacent nonprimary somatosensory fields. Confirming previous reports, neurons in this field had narrow tuning and were preferentially tuned to relatively low frequencies (<16 kHz). Intriguingly, auditory units in this field displayed shorter minimal latencies than units in the primary auditory cortex, as well as weaker sensitivity to deviance. These results establish the existence of a rapid auditory information stream with distinct properties through the insulo-parietal cortex that may parallel the pathway through the primary and anterior auditory fields.

Brain-machine interfaces (BMIs) offer a viable option for restoring function in patients with motor disabilities post-stroke. Most BMI systems rely on signals from the motor cortex (M1), which is often compromised after stroke. The cerebellum, a subcortical structure involved in motor control, remains an underexplored source for neuroprosthetic control. Using chronic electrophysiological recordings in a rat stroke model, we show that cerebellar neural activity can effectively drive BMI control, performing comparably to M1-driven control. We observed this even in animals with motor impairments post-stroke. Simultaneous M1-cerebellum recordings during cerebellar BMI control revealed that cerebellar "direct" neurons driving the interface were influenced by both local cerebellar and distant M1 neurons. While cerebellar influence remained stable, M1's interaction with cerebellar direct neurons shifted from longer to shorter timescales after stroke. These findings highlight that cerebellar direct neural control is possible in the stroke brain and reveal changes in M1-cerebellar network dynamics post-stroke.

Intracortical microelectrode arrays (MEAs) are vital tools for brain‐machine interface applications and basic neuroscience research, with the potential to advance treatments for neurological disorders and enhance the understanding of the nervous system. However, implanting intracortical electrodes can damage native tissue along the insertion path and trigger inflammatory responses characterized by neuronal loss and glial activation. While flexible electrodes reduce some of these adverse effects compared to rigid counterparts, their mechanical compliance often leads to buckling during insertion, necessitating the use of insertion aids such as stiff shuttles or dissolvable coatings. These aids, however, introduce additional complexity and can cause further tissue damage. In this work, microfabricated polyimide MEAs featuring a buckling‐resistant, trace‐stacked (BRATS) design are presented. It is demonstrated that BRATS MEAs can penetrate agarose brain phantoms and the rat cerebral cortex without the need for insertion aids. Once implanted, BRATS MEAs established a stable and functional electrical interface with the brain, enabling high‐fidelity, single‐unit electrophysiological recordings. Compared to conventional flexible MEAs inserted with a stiff shuttle, BRATS MEAs elicited significantly lower inflammatory responses and preserved a higher density of neurons near the implant site one week post‐implantation.

The central nervous system controls movement by combining neuromotor modules, known as muscle synergies. Previous studies suggest that spinal premotor interneurons (PreM‐INs) contribute to the encoding of stable muscle synergies for voluntary movement. But descending and sensory inputs also influence motor outputs through the spinal interneuronal network, which may be configured by its inputs to encode different sets of muscle synergies depending on the network state, thereby recruiting different selections of synergies. Here we tested this possibility of state‐dependent synergy encoding by examining the muscle synergies represented by the same upstream spinal interneurons under different activity states induced by various optogenetic stimulation patterns. Lumbosacral spinal units and electromyographic (EMG) activities of hindlimb muscles were simultaneously recorded from anaesthetized Thy1‐ChR2 mice as the spinal cord was stimulated by one or two optic fibres at different intensities. The synergy encoded by each unit was revealed as a ‘muscle field’ derived from spike‐triggered averages of EMG, whereas the entire muscle synergy set was factorized from the EMG. We found that although the muscle synergy set remained stable across stimulation conditions, the muscle fields of the same units were matched to different synergies within the set in different states. Thus the interneurons may flexibly adjust their connectivity with the motoneurons of the muscles as descending and sensory afferents impose different states on the spinal network. State‐dependent encoding of muscle synergies may allow different synergies to be selected for producing stable movement in an ever‐changing workspace environment. image Key points Muscle synergies for locomotion can be represented by spinal interneurons, as revealed by the interneurons’ muscle fields derived from spike‐triggered averages of EMG. The muscle field of a single spinal interneuron may vary under different stimulation conditions, as demonstrated by optogenetic stimulation. Encoding of muscle synergies is dependent on the state of spinal activities, thus facilitating the selection of appropriate synergies in different dynamic environments.

The neural mechanisms of consciousness remain elusive. Previous studies on both human and non-human animals, through manipulation of level of conscious arousal, have reported that specific time-series features correlate with level of consciousness, such as spectral power in certain frequency bands. However, such features often lack principled, theoretical justifications as to why they should be related with level of consciousness. This raises two significant issues: firstly, many other types of times-series features which could also reflect conscious level have been ignored due to researcher biases toward specific analyses; and secondly, it is unclear how to interpret identified features to understand the neural activity underlying consciousness, especially when they are identified from recordings which summate activity across large areas such as electroencephalographic recordings. To address the first concern, here we propose a new approach: in the absence of any theoretical priors, we should be maximally agnostic and treat as many known features as feasible as equally promising candidates. To apply this approach, we use h ighly c omparative t ime- s eries a nalysis ( hctsa ), a toolbox which provides over 7,700 different univariate time-series features originating from different research fields. To address the second issue, we employ hctsa to high-quality neural recordings from a relatively simple brain, the fly brain ( Drosophila melanogaster ), extracting features from local field potentials during wakefulness, general anesthesia, and sleep. At Stage 1 of this registered report, we constructed a classifier for each feature, for discriminating wakefulness and anesthesia in a discovery group of flies ( N = 13). At Stage 2, we assessed their performances on four independent groups of evaluation flies, from which recordings were made during anesthesia and sleep, and which were originally blinded to the data analysis team ( N = 49). We found only 47 time-series features, applied to recordings obtained from the center of the fly brain, to also significantly classify wake from anesthesia or sleep in all 4 of these evaluation datasets. Most of these were related to autocorrelation, and they indicated that signals during wakefulness remained correlated to their past for a longer timescale than during anesthesia and sleep. Meanwhile, time-series features related to well-known potential markers of consciousness, such as those related to complexity or spectral power, failed to generalize across all the flies. However, many of these complexity and spectral features have a consistent direction of effect due to anesthesia or sleep across flies, suggesting that even slight variations in experiment setup can reduce generalizability of classifiers. These results caution the current state of frequent discoveries of new potential consciousness markers, which may not generalize across datasets, and point to autocorrelation as a class of dynamical properties which does.

Intracortical microelectrodes are used for recording activity from individual neurons, providing both a valuable neuroscience tool and an enabling medical technology for individuals with motor disabilities. Standard neural probes carrying the microelectrodes are rigid silicon-based structures that can penetrate the brain parenchyma to interface with the targeted neurons. Unfortunately, within weeks after implantation, neural recording quality from microelectrodes degrades, owing largely to a neuroinflammatory response. Key contributors to the neuroinflammatory response include mechanical mismatch at the device-tissue interface and oxidative stress. We developed a mechanically-adaptive, resveratrol-eluting (MARE) neural probe to mitigate both mechanical mismatch and oxidative stress and thereby promote improved neural recording quality and longevity. In this work, we demonstrate that compared to rigid silicon controls, highly-flexible MARE probes exhibit improved recording performance, more stable impedance, and a healing tissue response. With further optimization, MARE probes can serve as long-term, robust neural probes for brain-machine interface applications.