Arousal

When we attend a demanding task, our performance is poor at low arousal (when drowsy) or high arousal (when anxious), but we achieve optimal performance at intermediate arousal. This celebrated Yerkes-Dodson inverted-U law relating performance and arousal is colloquially referred to as being "in the zone." In this talk, I will elucidate the behavioral and neural mechanisms linking arousal and performance under the Yerkes-Dodson law in a mouse model. During decision-making tasks, mice express an array of discrete strategies, whereby the optimal strategy occurs at intermediate arousal, measured

…these intrinsic and evoked dynamics is arousal, an internal state variable that determines an animal's level of engagement with its environment. In this work, we show that a continuous Hopfield network embellished with a single additional parameter---recurrent gain---captures some essential effects of arousal state at neural and cognitive levels. Using the model

The mammalian Prefrontal Cortex (PFC) has been suggested to modulate sensory information processing across multiple cortical regions via long-range axonal projections. These axonal projections arise from discrete PFC subregions with unique brain-wide connectivity and functional repertoires, which may provide the architecture for modular feedback intended to shape sensory processing. Here, we used axonal tracing, axonal and somatic 2-photon calcium imaging, and chemogenetic manipulations in mice to delineate how projections from the Anterior Cingulate Cortex (ACA) and ventrolateral Orbitofronta

…behavioral states of wakefulness and arousal, but the relationship between these two domains of function is not well understood. On one hand, serotonin activity is negatively associated with locomotor behavior, which has been seen as behavioral inhibition. On the other hand, serotonin transients are also associated with surprise or uncertainty, as well as novelty responses, including exploration-related facial movements (e.g., whisking, sniffing). Because ther

Arousal influences episodic memory retrieval, improving performance for arousing to-be-remembered stimuli, but its effect on later memory processes remains unclear. This functional Magnetic Resonance Imaging (fMRI) study investigated the effect of negative and positive arousal on memory of unrelated, neutral information presented following arousal exposure. Considering a decline in episodic memory retrieval and alterations in emotion regulation processes that occur in healthy ageing, we aimed to examine the effect of arousal on memory in young and old adults. Our findings indicate that both gr

Understanding the cellular mechanisms underlying learning and their alteration in Alzheimer’s disease (AD) is crucial for developing targeted therapies. We aimed to elucidate coordinated astrocytic and neuronal activities in learning, with a specific focus on their dynamics influenced by experience and alterations in AD. Using calcium imaging of neurons and astrocytes in the APP/PS1 double transgenic Alzheimer’s disease mouse model, we investigated behavioural and cellular responses to repetitive visual stimuli, in comparison with littermate wild type (WT) mice.We collected data from 32 female

(Jammal Salameh et al., Science_2024)​​Heartbeat transmission through the cerebral vascular system is known to cause intracranial pressure pulsations. Here we show for the first time that arterial pressure pulsations can directly modulate neuronal activity within the central nervous system via baroreceptive transduction. We recorded local-field-potentials (LFP) within the rat olfactory bulb (OB) using a semi-intact, perfused nose-brain preparation, while monitoring the pressure pulsations induced by the peristaltic perfusion pump that in our setup operated within the physiological range of hea

…We hypothesized that arousal, which impacts a variety of internal states and behaviours, could be one of these signals that orexin neurons transmit. To test this, we investigated the causal and correlative links between orexin neurons and pupil size, which is often taken as a readout of arousal. Optogenetic stimulation, 2-photon imaging, photometry, ablation, and pharmac

…pivotal role in modulating stress and arousal states. In the accompanying poster (Kota et al.), we defined several brain regions containing glutamatergic, GABAergic or mixed populations of neurons that project to PVT. In this study, we mapped cortical and subcortical afferents in the PVT and examined their distribution relative to the PVT/CR+ neuron population. We used vGLUT2-Cre, vGAT-Cre, and vGLUT2-Cre/vGAT-Flp double transgenic mouse strains to explore subcortical inputs via ant

…recently learned that locomotion and arousal strongly modulate visual processing, even at the retina level. Here, we aim to understand how locomotion impacts visual adaptation in the superior colliculus (SC), the most prominent visual centre in mice, which integrates retinal input in its superficial layers and performs sensorimotor transformations in its deeper layers. We r

Ascending neuromodulatory projections from deep brain nuclei generate internal brain states that differentially engage specific neuronal cell types. Because neurovascular coupling is cell-type specific and neuromodulatory transmitters have vasoactive properties, we hypothesized that the impulse response function (IRF) linking spontaneous neuronal activity with hemodynamics would depend on brain state. To test this hypothesis, we used mesoscopic optical imaging to measure (1) release of neuromodulatory transmitters norepinephrine (NE) or acetylcholine (ACh), (2) Ca2+ activity of local cortic

…locomotor region, and in arousal and sleep/wake states as part of theascending reticular activating system. In addition, several studies indicate that the PPN isinvolved in several other functions such as path integration, visual and auditory processing,attention and action-selection. As it was recently discovered thatoptogenetic stimulation of the rostral PPN can induce full body motor arrest, we wanted to investigateif this behavior was limited to motor output, or if sensory input was halt

Time perception can be distorted by factors such as arousal, attention or emotions. Recently, it has been demonstrated that stimulation of the vestibular system causes a contraction of subjective time (1). Conversely, the greater the amplitude of a whole-body rotation, the longer it seems to last, i.e. it causes a dilation of subjective time (2).To resolve this apparent inconsistency, and to better understand mechanisms of time perception during whole-body rotations, we evaluated time reproduction (2 or 4 seconds) in static (shakes) vs. two rotatory conditions (40° and 80°).The perceived time

The neurobiological mechanisms of arousal and anesthesia remain poorly understood. Recent evidence highlights the key role of interactions between the cerebral cortex and the diffusely projecting matrix thalamic nuclei. Here, we interrogate these processes in a whole-brain corticothalamic neural mass model endowed with targeted and diffusely projecting thalamocortical nuclei inferred from empirical data. This model captures key features seen in propofol anesthesia, including diminished network integration, lowered state diversity, impaired susceptibility to perturbation, and decreased corticoc

…theoretical framework that casts arousal as a dynamical process unfolding along a low-dimensional manifold that segreg

Recent work has shown that global signals related to arousal are embedded in the population activity of cortical neurons. In mice, slow fluctuations in neural activity are correlated with whisking and locomotion, while in monkeys a similar pattern has been identified (termed “slow drift”) that is: 1) present in visual/prefrontal cortices; 2) correlated with pupil size; and 3) associated with performance on cognitive tasks. These results demonstrate that changes in brain state are represented in the coordinated activity of cortical neurons. However, it is unknown if these fluctuations are also

…sensory decision-making and that arousal modulates task performance. However, it remains a challenge to understand (i) the relationships between arousal and task strategy during sensory discrimination and (ii) the neural mechanisms underlying optimal performance states. To address these topics, we combined behavioral, neurophysiological, and computational approaches to uncover the neural mechanisms underlying arousal-dependent sensory discrimination. We implemented two-alternative-choice tasks, prompting mi

Fluctuations in arousal, controlled by subcortical neuromodulatory systems, continuously shape cortical state, with profound consequences for information processing. Yet, how arousal signals influence cortical population activity in detail has so far only been characterized for a few selected brain regions. Traditional accounts conceptualize arousal as a homogeneous modulator of neural population activity across the cerebral cortex. Recent insights, however, point to a higher specificity of arousal effects on different components of neural activity and across cortical regions. Here, we provide

The arousal construct underlies a spectrum of behaviors that include sleep, exploration, feeding, sexual activity and adaptive stress. Pathological arousal conditions include stress, anxiety disorders, and addiction. The dynamics between arousal state transitions are modulated by norepinephrine neurons in the locus coeruleus, histaminergic neurons in the hypothalamus, dopaminergic neurons in the mesencephalon and cholinergic neurons in the basal forebrain. The hypocretin/orexin system in the lateral hypothalamus I will also present a new mechanism underlying sleep fragmentation during aging.

…fluctuations in internal states (e.g., arousal, attention, and motivation). Neural variability may reflect changes in these internal cognitive factors and can influence our perceptual and decision-making abilities. For instance, when tasked with shooting consecutive free throws on a basketball court, we may experience changes in our arousal, and our minds might wander. Such trial-to-trial variability can

…general functions of attention and arousal, recent studies using novel techniques to measure and manipulate this system with increasing exactitude have revealed intri

…inverted-U relationship between arousal and performance on signal detection tasks. However, there is currently a need for mechanistic models that can explain these state-dependent effects. Here we address this challenge in the context of arousal-dependent auditory processing in rodents. In experiments where mice were presented tones of different frequencies, we found that frequency information could be best decoded from popu

…to release NE ubiquitously to regulate arousal and attention. However, LC-NE is implicated in more precise roles such as mediating learning, promoting task execution, and signaling unexpected uncertainty. Whether and how LC-NE activity facilitates these distinct aspects of behavior is unknown. Here, we show that LC-NE activity displays distinct spatiotemporal dynamics to enable two functions during a learne

…While many arousal-associated neuromodulators—including norepinephrine (NE)—reduce cortical synchrony, how the cortex resynchronizes following NE signaling remains unknown. Using in vivo two-photon imaging and electrophysiology in mouse visual cortex, we describe a critical role for cortical astrocytes in circuit resynchronization. We characterize astrocytes’ sensitive calcium responses to changes in behavioral arousal and NE, identify that astrocyte signaling precedes in