Biology subjects

McGinley, M. J.

Publications and source records attributed to McGinley, M. J..

8 recordsLinked to original sources

bioRxiv2024

Combining pupillometry and drift-diffusion models reveals auditory category learning dynamics

Pupillometry and drift-diffusion models (DDM) have emerged as powerful tools to offer insights into learning processes and decisional dynamics. Specifically, pupillary dilation can serve as a metric of arousal and cognitive processing, and DDMs examine processes underlying perceptual decision-making using behavioral accuracies and response times. Methodological constraints have complicated the combination of the two methods in the study of learning. DDMs require precise response times, yet pupillary responses are slow and are impacted by motor movements. Here, we developed a learning task that separately optimized measurement of behavioral response times and pupil dilation during learning. We modified a standard learning paradigm to include trials with and without timing delays between stimulus presentation and response. Delayed trials optimized measurement of the pupil, while immediate trials optimized behavioral response times. We tested whether decision-making processes estimated with DDMs could be recovered from delayed trials where pupil response measurement was optimized. Our results indicated that pupil responses on delayed trials showed distinct markers of learning that were not present on immediate trials. DDM parameters from delayed trials also showed expected trends for learning. Finally, we demonstrated that DDM parameters elicit differential pupillary responses. Together, these results indicate that learning dynamics and decisional processes can be decoded from pupillary responses.

physiology↗

bioRxiv2023

Simultaneously-recorded cholinergic axons and cortical acetylcholine are highly correlated with pupil size and locomotion under spontaneous conditions

Even under spontaneous conditions and in the absence of changing environmental demands, awake animals alternate between increased or decreased periods of alertness. These changes in brain state can occur rapidly, on a timescale of seconds, and neuromodulators such as acetylcholine (ACh) are thought to play an important role in driving these spontaneous state transitions. Here, we perform the first simultaneous imaging of ACh sensors and GCaMP-expressing axons in vivo, to examine the spatiotemporal properties of cortical ACh activity and release during spontaneous changes in behavioral state. We observed a high correlation between simultaneously recorded basal forebrain axon activity and neuromodulator sensor fluorescence around periods of locomotion and pupil dilation. Consistent with volume transmission of ACh, increases in axon activity were accompanied by increases in local ACh levels that fell off with the distance from the nearest axon. GRAB-ACh fluorescence could be accurately predicted from axonal activity alone, providing the first validation that neuromodulator axon activity is a reliable proxy for nearby neuromodulator levels. Deconvolution of fluorescence traces allowed us to account for the kinetics of the GRAB-ACh sensor and emphasized the rapid clearance of ACh for smaller transients outside of running periods. Finally, we trained a predictive model of ACh fluctuations from the combination of pupil size and running speed; this model performed better than using either variable alone, and generalized well to unseen data. Overall, these results contribute to a growing understanding of the precise timing and spatial characteristics of cortical ACh during fast brain state transitions.

neuroscience↗

bioRxiv2023

Comprehensively defining cellular specializations for initiating parallel auditory pathways in the mouse cochlear nucleus

The cochlear nuclear complex (CN), the starting point for all central auditory processing, comprises a suite of neuronal cell types that are highly specialized for neural coding of acoustic signals, yet molecular logic governing cellular specializations remains unknown. By combining single-nucleus RNA sequencing and Patch-seq analysis, we reveal a set of transcriptionally distinct cell populations encompassing all previously observed types and discover multiple new subtypes with anatomical and physiological identity. The resulting comprehensive cell-type taxonomy reconciles anatomical position, morphological, physiological, and molecular criteria, enabling the determination of the molecular basis of the remarkable cellular phenotypes in the CN. In particular, CN cell-type identity is encoded in a transcriptional architecture that orchestrates functionally congruent expression across a small set of gene families to customize projection patterns, input-output synaptic communication, and biophysical features required for encoding distinct aspects of acoustic signals. This high-resolution account of cellular heterogeneity from the molecular to the circuit level illustrates molecular logic for cellular specializations and enables genetic dissection of auditory processing and hearing disorders with unprecedented specificity.

neuroscience↗

bioRxiv2022

Auditory accessory stimulus boosts pupil-linked arousal and reduces choice bias

AO_SCPLOWBSTRACTC_SCPLOWRecent work indicates that pupil-linked phasic arousal signals reduce the impact of prior expectations and biases on decision formation. It has remained unclear whether phasic arousal (i) causes the bias reduction, if (ii) choosing against ones bias causes phasic arousal, or if (iii) a third variable is driving both. Here, using an auditory accessory stimulus, we found evidence for the first scenario: on accessory stimulus vs normal trials, pupil-linked phasic arousal was robustly elevated and choice bias was reduced. With computational modeling of behavior, we established that the bias reduction was not due to a change in response caution (i.e., speed-accuracy tradeoff), but due to a change in a bias in the accumulation of evidence leading up to a choice. Thus, pupil-linked phasic arousal shapes choice behavior.

neuroscience↗

bioRxiv2022

Mice regulate their attentional intensity and arousal to exploit increases in task utility

Changes in autonomic arousal, such as mounting sleep pressure, and changes in motivation, such as fluctuating environmental reward statistics, both profoundly influence behavior. Our experience tells us that we have some capacity to control our arousal when doing so is important, such as staying awake while driving a motor vehicle. However, little is known about how decision computations are jointly influenced by arousal and motivation, including whether animals, such as rodents, can adapt their arousal state to their needs. Here, we developed and show results from an auditory feature-based sustained-attention task with intermittently shifting task utility. We use pupil size to estimate arousal across a wide range of states and apply novel signal detection theoretic and accumulation-to-bound modeling approaches in a large behavioral cohort. We find that both pupil-linked arousal and task utility have major impacts on multiple aspects of performance. Although substantial arousal fluctuations persist across utility conditions, mice partially stabilize their arousal near an intermediate, and optimal, level when task utility is high. Behavioral analyses show that multiple elements of behavior improve during high task utility and that arousal influences some, but not all, of them. Specifically, arousal influences the likelihood and timescale of sensory evidence accumulation, but not the quantity of evidence accumulated per time step while attending. In sum, the results establish specific decision-computational signatures of arousal, motivation, and their interaction, in attention. So doing, we provide an experimental and analysis framework for studying arousal self-regulation in neurotypical brains and diseases such as attention-deficit/hyperactivity disorder.

neuroscience↗

bioRxiv2022

Vagus nerve stimulation recruits the central cholinergic system to enhance perceptual learning

Perception can be refined by experience up to certain limits. It is unclear if perceptual limitations are absolute or could be partially overcome via enhanced neuromodulation and/or plasticity. Recent studies suggest the utility of peripheral nerve stimulation - specifically vagus nerve stimulation (VNS) - for altering neural activity and augmenting experience-dependent plasticity, although little is known about central mechanisms recruited by VNS. Here we developed an auditory discrimination task for mice implanted with a VNS electrode. VNS occurring during behavior gradually improved discrimination abilities beyond the level achieved by training alone. Using two-photon imaging, we identified changes to auditory cortical responses and activation of cortically-projecting cholinergic axons with VNS. Anatomical and optogenetic experiments indicated that VNS could enhance task performance via activation of the central cholinergic system. These results highlight the importance of cholinergic modulation for the efficacy of VNS, perhaps enabling further refinement of VNS methodology for clinical conditions.

neuroscience↗

bioRxiv2019

Graded recruitment of pupil-linked neuromodulation by parametric stimulation of the vagus nerve

AO_SCPLOWBSTRACTC_SCPLOWVagus nerve stimulation (VNS) is thought to affect neural activity by recruiting brain-wide release of neuromodulators. VNS is used in treatment-resistant epilepsy, and is increasingly being explored for other disorders, such as depression, and as a cognitive enhancer. However, the promise of VNS is only partially fulfilled due to a lack of mechanistic understanding of the transfer function between stimulation parameters and neuromodulatory response, together with a lack of biosensors for assaying stimulation efficacy in real time. We here develop an approach to VNS in head-fixed mice on a treadmill and show that pupil dilation is a reliable and convenient biosensor for VNS-evoked cortical neuromodulation. In an optimal zone of stimulation parameters, current leakage and off-target effects are minimized and the extent of pupil dilation tracks VNS-evoked basal-forebrain cholinergic axon activity in neocortex. Thus, pupil dilation is a sensitive readout of the moment-by-moment, titratable effects of VNS on brain state.

neuroscience↗

bioRxiv2018

Phasic arousal optimizes decision computations in mice and humans

Decisions are often made by accumulating ambiguous evidence over time. The brains arousal systems are activated during such decisions. In previous work in humans, we showed that evoked responses of arousal centers during decisions are reported by rapid dilations of the pupil, and predict a suppression of biases in the accumulation of decision-relevant evidence (de Gee et al. 2017). Here, we show that this arousal-related suppression in decision bias acts on both conservative and liberal biases, and generalizes across species (humans / mice), sensory systems (visual / auditory), and domains of decision-making (perceptual / memory-based). In challenging sound-detection tasks, the impact of spontaneous or experimentally induced choice biases was reduced under high arousal. Similar bias suppression occurred when evidence was drawn from memory. All these behavioral effects were explained by reduced evidence accumulation biases. Our results pinpoint a general principle of the interplay between phasic arousal and decision-making.

neuroscience↗