Biology subjects

Borden, P. Y.

Publications and source records attributed to Borden, P. Y..

6 recordsLinked to original sources

bioRxiv2022

Cortical networks relating to arousal are differentially coupled to neural activity and hemodynamics

Even in the absence of specific sensory input or a behavioral task, the brain produces structured patterns of activity. This organized activity is modulated by changes in arousal. Here, we use wide-field voltage imaging to establish how arousal relates to cortical network voltage and hemodynamic activity in spontaneously behaving head-fixed male and female mice expressing the voltage-sensitive fluorescent FRET sensor Butterfly 1.2. We find that global voltage and hemodynamic signals are both positively correlated with changes in arousal with a maximum correlation of 0.5 and 0.25 respectively at a time lag of 0 seconds. We next show that arousal influences distinct cortical regions for both voltage and hemodynamic signals. These include a broad positive correlation across most sensory-motor cortices extending posteriorly to the primary visual cortex observed in both signals. In contrast, activity in prefrontal cortex is positively correlated to changes in arousal for the voltage signal while it is a slight net negative correlation observed in the hemodynamic signal. Additionally, we show that coherence between voltage and hemodynamic signals relative to arousal is strongest for slow frequencies below 0.15 Hz and is near zero for frequencies greater than 1Hz. We finally show that coupling patterns are dependent on the behavioral state of the animal with correlations being driven by periods of increased orofacial movement. Our results indicate that while hemodynamic signals show strong relations to behavior and arousal, these relations are distinct from those observed by voltage activity. Significance StatementWe leverage wide-field voltage imaging to examine the relation between cortical changes in membrane potential dynamics and hemodynamics. These two signals are then examined with respect to changes in arousal, as measured by pupil diameter, in awake head fixed mice. Our results show similarities as well as important differences in the correlation of arousal with neuronal population activity dynamics and the hemodynamic signal. Further, the spatial activity correlation maps with arousal depended differentially on the behavioral state of the animal in a frequency dependent manner. Our results indicate that the modulation of brain networks by arousal is dynamically regulated, and only partly overlap between functional networks determined from hemodynamic or voltage activity.

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↗

bioRxiv2021

Adaptive Behavior and the Role of Primary Somatosensory Cortex

Behavioral experience and flexibility are crucial for survival in a constantly changing environment. Despite evolutionary pressures to develop adaptive behavioral strategies in a dynamically changing sensory landscape, the underlying neural correlates have not been well explored. Here, we use genetically encoded voltage imaging to measure signals in primary somatosensory cortex (S1) during sensory learning and behavioral adaptation in the mouse. In response to changing stimulus statistics, mice adopt a strategy that modifies their detection behavior in a context dependent manner as to maintain reward expectation. Surprisingly, neuronal activity in S1 shifts from simply representing stimulus properties to transducing signals necessary for adaptive behavior in an experience dependent manner. Our results suggest that neuronal signals in S1 are part of an adaptive framework that facilitates flexible behavior as individuals gain experience, which could be part of a general scheme that dynamically distributes the neural correlates of behavior during learning.

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

Unilateral optogenetic inhibition and excitation of basal ganglia output show opposing effects on left/right lick choices and movement initiation in mice

Models of basal ganglia function predict that tonic inhibitory output to motor thalamus suppresses unwanted movements, and that a decrease in such activity leads to action selection. A direct test of these outcomes of thalamic inhibition has not been performed, however. To conduct such a direct test, we utilized rapid optogenetic activation and inactivation of the GABAergic output of the substantia nigra pars reticulata (SNr) to motor thalamus in mice that were trained in a sensory cued left/right licking task. Directional licking tasks have previously been shown to depend on a thalamocortical feedback loop between ventromedial motor thalamus and antero-lateral premotor cortex (Li et al., 2015; Guo et al., 2017). In confirmation of model predictions, we found that 1s of unilateral optogenetic inhibition of GABAergic output from the SNr biased decision making towards the contralateral lick spout with ipsilaterally cued trials while leaving motor performance intact. In contrast, 1s of optogenetic excitation of SNr terminals in motor thalamus resulted in an opposite bias towards the ipsilateral direction confirming a bidirectional effect of tonic nigral output on directional decision making. In a second variant of the task we disallowed anticipatory licking and found that successful suppression of anticipatory licking was also impacted by our optogenetic manipulations in agreement with the suppressive effect of tonic nigral output. Nevertheless, direct unilateral excitation of SNr cell bodies resulted in bilateral movement suppression, suggesting that descending motor pathways from the SNr to superior colliculus also play an important role in the control of licking behavior.\n\nSignificance StatementThis study provides the first evidence that basal ganglia output to motor thalamus can control decision making in left/right licking choices and suppress anticipatory movement initiation. Unilateral optogenetic inhibition or excitation of basal ganglia output via the substantia nigra resulted in opposite changes of directional lick choices and could override the sensory information on lick direction provided by a whisker stimulus. These results suggest that basal ganglia output gates activity in a thalamo-cortical feedback loop previously shown to underlie the control of forced choice directional licking behavior. The results substantiate models stating that tonic inhibition of motor thalamus from the basal ganglia directs action selection and suppresses unwanted movements.

neuroscience↗