Biology subjects

Wright, N. C.

Publications and source records attributed to Wright, N. C..

10 recordsLinked to original sources

bioRxiv2024

Multiple distinct timescales of rapid sensory adaptation in the thalamocortical circuit

Numerous studies have shown that neuronal representations in sensory pathways are far from static but are instead strongly shaped by the complex properties of the sensory inputs they receive. Adaptation dynamically shapes the neural signaling that underlies our perception of the world yet remains poorly understood. We investigated rapid adaptation across timescales from hundreds of milliseconds to seconds through simultaneous multi-electrode recordings from the ventro-posteromedial nucleus of the thalamus (VPm) and layer 4 of the primary somatosensory cortex (S1) in male and female anesthetized mice in response to controlled, persistent whisker stimulation. Observations in VPm and S1 reveal a degree of adaptation that progresses through the pathway. Signatures of two distinct timescales of rapid adaptation in the firing rates of both thalamic and cortical neuronal populations were revealed, also reflected in the synchrony of the thalamic population and in the thalamocortical synaptic efficacy that was measured in putatively monosynaptically connected thalamocortical pairs. Controlled optogenetic activation of VPm further demonstrated that the longer timescale adaptation observed in S1 is likely inherited from slow decreases in thalamic firing rate and synchrony. Despite the degraded sensory responses, adaptation resulted in a shift in coding strategy that favors theoretical discrimination over detection across the observed timescales of adaptation. Overall, although multiple mechanisms contribute to rapid adaptation at distinct timescales, they support a unifying framework on the role of adaptation in sensory processing. Significance StatementAlthough the perceptual effects of persistent sensory stimulation have been known for centuries, the rapid sensory adaptation of the underlying neural signaling to these persistent inputs are not well understood. Here, we present evidence for two distinct timescales of adaptation over several seconds across the thalamocortical circuit in mice. We identify both the overall level of neural activity and the corresponding population synchrony of the thalamic inputs to primary somatosensory cortex as key role players shaping the cortical adaptation.

neuroscience↗

bioRxiv2023

Dynamic corticothalamic modulation of the somatosensory thalamocortical circuit during wakefulness

The feedback projections from cortical layer 6 (L6CT) to sensory thalamus have long been implicated in playing a primary role in gating sensory signaling but remain poorly understood. To causally elucidate the full range of effects of these projections, we targeted silicon probe recordings to the whisker thalamocortical circuit of awake mice selectively expressing Channelrhodopsin-2 in L6CT neurons. Through optogenetic manipulation of L6CT neurons, multi-site electrophysiological recordings, and modeling of L6CT circuitry, we establish L6CT neurons as dynamic modulators of ongoing spiking in the ventro-posterior-medial nucleus of thalamus (VPm), either suppressing or enhancing VPm spiking depending on L6CT neurons firing rate and synchrony. Differential effects across the cortical excitatory and inhibitory sub-populations point to an overall influence of L6CT feedback on cortical excitability that could have profound implications for regulating sensory signaling across a range of ethologically relevant conditions.

neuroscience↗

bioRxiv2021

Thalamic state controls timing and synchronization of primary somatosensory cortical representations in the awake mouse

The thalamus controls transmission of sensory signals from periphery to cortex, ultimately shaping perception. Despite this significant role, dynamic thalamic gating and the consequences for downstream cortical sensory representations have not been well studied in the awake brain. We optogenetically modulated the ventro-posterior medial thalamus in the vibrissa pathway of the awake mouse, and measured spiking activity in the thalamus, and activity in primary somatosensory cortex (S1) using extracellular electrophysiology and genetically encoded voltage imaging. Thalamic hyperpolarization significantly enhanced thalamic sensory-evoked bursting, yet surprisingly the S1 cortical response was not amplified, but instead timing precision was significantly increased, spatial activation more focused, and there was an increased synchronization of cortical inhibitory neurons. A thalamocortical network model implicates the modulation of precise timing of feedforward thalamic population spiking, presenting a highly sensitive, timing-based gating of sensory signaling to cortex.

neuroscience↗

bioRxiv2020

Rapid Cortical Adaptation and the Role of Thalamic Synchrony During Wakefulness

Rapid sensory adaptation is observed across all sensory systems, and strongly shapes sensory percepts in complex sensory environments. Yet despite its ubiquity and likely necessity for survival, the mechanistic basis is poorly understood. A wide range of primarily in-vitro and anesthetized studies have demonstrated the emergence of adaptation at the level of primary sensory cortex, with only modest signatures in earlier stages of processing. The nature of rapid adaptation and how it shapes sensory representations during wakefulness, and thus the potential role in perceptual adaptation, is underexplored, as are the mechanisms that underlie this phenomenon. To address these knowledge gaps, we recorded spiking activity in primary somatosensory cortex (S1) and the upstream ventral posteromedial (VPm) thalamic nucleus in the vibrissa pathway of awake male and female mice, and quantified responses to whisker stimuli delivered in isolation and embedded in an adapting sensory background. We found that cortical sensory responses were indeed adapted by persistent sensory stimulation; putative excitatory neurons were profoundly adapted, and inhibitory neurons only modestly so. Further optogenetic manipulation experiments and network modeling suggest this largely reflects adaptive changes in synchronous thalamic firing combined with robust engagement of feedforward inhibition, with little contribution from synaptic depression. Taken together, these results suggest that cortical adaptation in the regime explored here results from changes in the timing of thalamic input, and the way in which this differentially impacts cortical excitation and feedforward inhibition, pointing to a prominent role of thalamic gating in rapid adaptation of primary sensory cortex. Significance StatementRapid adaptation of sensory activity strongly shapes representations of sensory inputs across all sensory pathways over the timescale of seconds, and has profound effects on sensory perception. Despite its ubiquity and theoretical role in the efficient encoding of complex sensory environments, the mechanistic basis is poorly understood, particularly during wakefulness. In this study in the vibrissa pathway of awake mice, we show that cortical representations of sensory inputs are strongly shaped by rapid adaptation, and that this is mediated primarily by adaptive gating of the thalamic inputs to primary sensory cortex and the differential way in which these inputs engage cortical sub-populations of neurons.

neuroscience↗

bioRxiv2020

Compensation of physiological motion enables high-yield whole-cell recording in vivo

1.1.1Whole-cell patch-clamp recording in vivo is the gold-standard method for measuring subthreshold electrophysiology from single cells during behavioural tasks, sensory stimulations, and optogenetic manipulation. However, these recordings require a tight, gigaohm resistance, seal between a glass pipette electrodes aperture and a cells membrane. These seals are difficult to form, especially in vivo, in part because of a strong dependence on the distance between the pipette aperture and cell membrane. We elucidate and utilize this dependency to develop an autonomous method for placement and synchronization of pipettes tip aperture to the membrane of a nearby, moving neuron, which enables high-yield seal formation and subsequent recordings in the deep in the brain of the living mouse, in the thalamus. This synchronization procedure nearly doubles the reported gigaseal yield in the thalamus (>3 mm below the pial surface) from 26% (n=17/64) to 48% (n=32/66). Whole-cell recording yield improved from 10% (n = 9/88) to 24% (n=18/76) when motion compensation was used during the gigaseal formation. As an example of its application, we utilized this system to investigate the role of the sensory environment and ventral posterior medial region (VPM) projection synchrony on intracellular dynamics in the barrel cortex. This method results in substantially greater subcortical whole-cell recording yield than previously reported and thus makes pan-brain whole-cell electrophysiology practical in the living mouse brain.

neuroscience↗

bioRxiv2018

Single-cell membrane potential fluctuations evince network scale-freeness and quasicriticality

What information single neurons receive about general neural circuit activity is a fundamental question for neuroscience. Somatic membrane potential fluctuations are driven by the convergence of synaptic inputs from a diverse cross-section of upstream neurons. Furthermore, neural activity is often scale-free implying that some measurements should be the same, whether taken at large or small scales. Together, convergence and scale-freeness support the hypothesis that single membrane potential recordings carry useful information about high-dimensional cortical activity. Conveniently, the theory of \"critical branching networks\" (a purported explanation for scale-freeness) provides testable predictions about scale-free measurements which are readily applied to membrane potential fluctuations. To investigate, we obtained whole-cell current clamp recordings of pyramidal neurons in visual cortex of turtles with unknown genders. We isolated fluctuations in membrane potential below the firing threshold and analyzed them by adapting the definition of \"neuronal avalanches\" (spurts of population spiking). The membrane potential fluctuations we analyzed were scale-free and consistent with critical branching. These findings recapitulated results from large-scale cortical population data obtained separately in complementary experiments using microelectrode arrays (previously published (Shew et al., 2015)). Simultaneously recorded single-unit local field potential did not provide a good match; demonstrating the specific utility of membrane potential. Modeling shows that estimation of dynamical network properties from neuronal inputs is most accurate when networks are structured as critical branching networks. In conclusion, these findings extend evidence for critical branching while also establishing subthreshold pyramidal neuron membrane potential fluctuations as an informative gauge of high-dimensional cortical population activity.

neuroscience↗

bioRxiv2017

Visual Response Properties In The Three Layer Turtle Visual Cortex

Turtle dorsal cortex provides us with unique insights into cortical processing. It is known to share many features with the mammalian hippocampus and olfactory cortex as well as geniculo-cortical areas in stem amniotes from which mammals evolved. To this end, we have used data from extracellular recordings from microelectrode arrays to study spatial and temporal patterns of responses to visual stimuli as seen in both local field potential and action potentials. We discovered surprisingly large receptive fields, responsiveness to a broad range of stimuli, and high correlation between distant neural ensembles across recording array. Moreover, we found significant response variability regarding latency and strength in the presence of adaptation to both ongoing and visually evoked activity.

neuroscience↗

bioRxiv2016

Network activity influences the subthreshold and spiking visual responses of pyramidal neurons in a three-layer cortex

A primary goal of systems neuroscience is to understand cortical function, which typically involves studying spontaneous and sensory-evoked cortical activity. Mounting evidence suggests a strong and complex relationship between the ongoing and evoked state. To date, most work in this area has been based on spiking in populations of neurons. While advantageous in many respects, this approach is limited in scope; it records the activities of a minority of neurons, and gives no direct indication of the underlying subthreshold dynamics. Membrane potential recordings can fill these gaps in our understanding, but are difficult to obtain in vivo. Here, we record subthreshold cortical visual responses in the ex vivo turtle eye-attached whole-brain preparation, which is ideally-suited to such a study. In the absence of visual stimulation, the network is \"synchronous\"; neurons display network-mediated transitions between low- and high-conductance membrane potential states. The prevalence of these slow-wave transitions varies across turtles and recording sessions. Visual stimulation evokes similar high-conductance states, which are on average larger and less reliable when the ongoing state is more synchronous. Responses are muted when immediately preceded by large, spontaneous high-conductance events. Evoked spiking is sparse, highly variable across trials, and mediated by concerted synaptic inputs that are in general only very weakly correlated with inputs to nearby neurons. Together, these results highlight the multiplexed influence of the cortical network on the spontaneous and sensory-evoked activity of individual cortical neurons.

neuroscience↗

bioRxiv2016

Response variability and population coupling of cortical synaptic inputs are strongly influenced by network properties

The highly variable spiking of a cortical neuron is \"coupled\" to that of other neurons in the network. This has implications for sensory coding, and appears to represent a fundamental property of cortical sensory processing. To date, most studies of population coupling have focused on recorded spiking activity, an approach that suffers from several confounding issues. Moreover, the contributions of various network properties to population coupling are largely unexplored. To this end, we recorded the membrane potential (V) and the nearby LFP in the visual cortex of the turtle ex vivo wholebrain preparation during ongoing and visually-evoked activity. We used an algorithm to infer the excitatory conductance (g) from V, and calculated the g-LFP coupling. We found that g-LFP coupling was highly variable across neurons, and increased following visual stimulation before relaxing to intermediate values. To investigate the role of the network, we implemented a driven small-world network of leaky integrate-and-fire neurons. This model reproduces the large across-trial response variability and g-LFP coupling dynamic, and suggests crucial roles for anatomical and emergent network properties.

neuroscience↗

bioRxiv2016

Adaptation modulates correlated response variability in visual cortex

Cortical sensory responses are highly variable across stimulus presentations. This variability can be correlated across neurons (due to some combination of dense intracortical connectivity, cortical activity level, and cortical state), with fundamental implications for population coding. Yet the interpretation of correlated response variability (or \"noise correlation\") has remained fraught with difficulty, in part because of the restriction to extracellular neuronal spike recordings. Here, we measured response variability and its correlation at the most microscopic level of electrical neural activity, the membrane potential, by obtaining dual whole-cell recordings from pairs of cortical pyramidal neurons during visual processing. We found that during visual stimulation, correlated variability adapts towards an intermediate level and that this correlation dynamic is mediated by intracortical mechanisms. A model network with external inputs, synaptic depression, and structure reproduced the observed dynamics of correlated variability. These results establish that intracortical adaptation self-organizes cortical circuits towards a balanced regime at which network coordination maintains an intermediate level.

neuroscience↗