Strategic stabilization of arousal boosts sustained attention

bioRxiv (Cold Spring Harbor Laboratory), Год журнала: 2022, Номер unknown

Опубликована: Март 6, 2022

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

Язык: Английский

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Electrophysiological correlates of attention in the locus coeruleus - anterior cingulate cortex circuit during the rodent continuous performance test

bioRxiv (Cold Spring Harbor Laboratory), Год журнала: 2023, Номер unknown

Опубликована: Апрель 20, 2023

ABSTRACT Sustained attention, the ability to focus on an activity or stimulus over time, is significantly impaired in many psychiatric disorders, and there remains a major unmet need treating attention. Continuous performance tests (CPTs) were developed measure sustained attention humans, non-human primates, rats, mice, similar neural circuits are engaged across species during CPT performance, supporting their use translational studies identify novel therapeutics. Here, we identified electrophysiological correlates of attentional touchscreen-based rodent (rCPT) locus coeruleus (LC) anterior cingulate cortex (ACC), two inter-connected regions that implicated processes. We used viral labeling molecular techniques demonstrate recruited LC-ACC projections rCPT, this recruitment increases with cognitive demand. implanted male mice depth electrodes within LC ACC for local field potential (LFP) recordings rCPT training, increase delta theta power, power correct responses rCPT. also found leads frequencies while gamma incorrect responses. These findings may represent biomarkers can be screen therapeutics drug discovery

Язык: Английский

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Stimulation of locus coeruleus inputs to the frontal cortex in mice induces cell type-specific expression of the Apoe gene

bioRxiv (Cold Spring Harbor Laboratory), Год журнала: 2024, Номер unknown

Опубликована: Июль 23, 2024

Abstract Deficits in attention are common across a range of neuropsychiatric disorders. A multitude brain regions, including the frontal cortex (FC) and locus coeruleus (LC), have been implicated attention. Regulators these regions at molecular level not well understood, but might elucidate underlying mechanisms disorders with attentional deficits. To probe this, we used chemogenetic stimulation neurons LC axonal projections to FC, subsequent bulk RNA-sequencing from mouse FC. We found that this circuit caused an increase transcription Apoe gene. investigate cell type-specific expression dual-virus approach express either excitatory DREADD receptor hM3Dq or control virus, increases FC following depolarization inputs is enriched GABAergic sex-dependent manner. The results experiments yield insights into how affects function cortical microcircuits important for attention-guided behavior, point interneuron-specific as potential target amelioration symptoms such attention-deficit hyperactivity disorder (ADHD), schizophrenia, Alzheimer’s disease (AD). Significance Statement Identifying patterns gene specific circuits first step toward developing treatments cognitive behavioral rely on those circuits. In paper, describe transcriptome-scale motif one - project This has attention, deficits many disorders, suggesting targeting could therapeutic ameliorating further explored top differentially expressed genes, Apoe, identify it distinct types circuit, paving way spatially- genetically-specific

Язык: Английский

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Strategic stabilization of arousal boosts sustained attention

Current Biology, Год журнала: 2024, Номер 34(18), С. 4114 - 4128.e6

Опубликована: Авг. 15, 2024

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

Язык: Английский

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The Projection-Specific Noradrenergic Modulation of Perseverative Spatial Behavior in Adult Male Rats

eNeuro, Год журнала: 2024, Номер 11(8), С. ENEURO.0063 - 24.2024

Опубликована: Авг. 1, 2024

Adaptive behavior relies on efficient cognitive control. The anterior cingulate cortex (ACC) is a key node within the executive prefrontal network. reciprocal connectivity between locus ceruleus (LC) and ACC thought to support behavioral reorganization triggered by detection of an unexpected change. We transduced LC neurons with either excitatory or inhibitory chemogenetic receptors in adult male rats trained spatial task. Subsequently, we altered activity confronted change reward locations. In new context, decreased noradrenaline (NA) entered unbaited maze arms more persistently which was indicative perseveration. contrast, suppression global NA transmission reduced Neither manipulation nor inactivation muscimol affected rate learning, possibly due partial virus transduction and/or compensatory engagement other regions. Importantly, observed deficits damage caused injection. latter finding highlights importance careful histological assessment virus-transduced brain tissue as inadvertent targeted cell population neurotoxicity factors might cause unwanted side effects. Although specific role flexibility has not been convincingly demonstrated, our results beneficial noradrenergic for optimal function ACC. Overall, findings suggest exerts projection-specific modulation neural circuits mediating behavior.

Язык: Английский

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