Norepinephrine

Animals constantly decide how to allocate mental resources to thrive in their environments. Managing learning is a key challenge, and recent experiments show that animals often incur attentional costs for the potential of greater future rewards, or disengage when a task appears unlearnable, exhibiting nuanced cognitive control over learning. However, optimizing time-dependent control requires complex computations, including integrating an agent's learning dynamics and predicting how control affects future rewards. Here, we present a solution for optimal control of integrated non-linear learnin

…regulated by the neuromodulator norepinephrine, can cause both attentiveness and anxiety. Thus, adaptive decision making that scales with threat valence is crucial. To study proper decision-making under threat and the role of norepinephrine, we developed a novel task in which mice descend from a height toward an illusion of safe and unsafe visual cues. This virtual stimulus --- where there is a mismatch between actual safety and perceived safety --- relies on the evolutionarily conserved, innate fe

cAMP is a ubiquitous second messenger and plays a central role in the regulation of gene expression and synaptic transmission. While calcium imaging is a well-established technique with a variety of different chemical and genetically encoded sensors, cAMP sensors have been lacking until recently and hence cAMP signaling is not well studied in astrocytes so far. Flamindo2 from Odaka et al. (PLOS One 9:6, 2014) is a genetically encoded cAMP sensor, which fluorescence intensity decreases in response to increased cAMP levels. In this study we investigated noradrenergic cAMP signaling in astrocytes

Internal states and behavior are associated with brain-wide changes in the activity of neuronal circuits. Such global shifts are believed to be implemented by changes in neuromodulatory tone. Neuromodulators originate from a few neurons and are released widely throughout the brain to alter the function of target circuits.The amygdala plays an essential role in the processing of emotional stimuli. Salience and synaptic alterations in this region are critical for emotional processing and learning. The amygdala is innervated by all major neuromodulators, yet we know little about the dynamics of n

Locus Coeruleus (LC) is a neuromodulatory system that is heavily affected at an early stage of Alzheimer´s Disease (AD) progression. In human AD patients, the LC shows an extensive loss of neurons. Therefore, the goals of this project are to examine the influence of the LC on HPC-dependent mnemonic processes and on their impairment in AD. To achieve this, we explored, whether the structural and functional connectivity between the LC and the HPC is altered in an APPswe/PSEN1dE9 mouse model of AD. We found a significant reduction of LC to HPC projections identified by immunohistochemically stain

Norepinephrine (NE) is one of the main neuromodulators in the brain influencing a plethora of behavioral outputs including both autonomic and cognitive functions, such as emotional learning and stress responses, through a brain-wide network of projections emanating from the Locus Coeruleus (LC). Genetically encoded indicators engineered from G-protein-coupled receptors (GPCRs) have been proven essential tools for neuroscience enabling in vivo imaging of neuromodulators with high spatiotemporal resolution. Current state-of-the-art NE sensors allow for in vivo optical detection of NE, however, t

…critical role in behavior by supplying norepinephrine to the brain. Understanding how LC-NA neurons are regulated is essential to understanding the role of the LC-NA system in behavior. Since previous studies have identified a population of inhibitory pre-LC neurons that regulate LC-NA neurons, this study investigates whether there are excitatory pre-LC neurons responsible for the regulation of LC-NA neurons. We infused AAVs into the LC of TH-Cre crossed with vGluT2-FLP mice expressing wheat germ agglutinin (WGA) and eYFP in a Cre-

We aimed to investigate the role of dopamine (DA), acetylcholine (ACh), norepinephrine (NE) and serotonin (5-HT) in associative learning and the correlation of their release with the reward prediction error (RPE). To address this, we trained mice on a sound detection Pavlovian conditioning task with a 50% reward schedule that allowed examining clean representations of postivite (rewarded trials) and negative RPE (reward omission trials), while we measured DA, ACh, NE and 5-HT release by fiber photometry. Behavioral updating of value representations based on the outcome of the previous trial wa

…of neuromodulatory transmitters norepinephrine (NE) or acetylcholine (ACh), (2) Ca2+ activity of local cortic

The different behavioral states inherent to the wake-sleep cycle are reflected in the electrical activity of the cerebral cortex. Slow-wave sleep (SWS) and deep anesthesia are dominated by high amplitude slow-wave oscillations (SWO, < 1 Hz). With the increase in arousal, desynchronization and low-amplitude fast rhythms arise. While SWS and wakefulness dynamics have been comprehensively described, their transition remains relatively unexplored. Tort-Colet et al (2021) previously reported the emergence of an intermediate brain state, the microarousal brain state, characterized by the rhythmic

The formation of new inhibitory synapses is essential to counterbalance a strong excitatory activity and maintain dendritic coordination between excitation and inhibition. We recently demonstrated that the activation of excitatory spines is followed by the production of endocannabinoids in dendrites, which mediates the formation of new inhibitory boutons via axonal CB1 receptors. Bouton formation was found to depend on an increase of the second messenger cyclic adenosine monophosphate (cAMP) and the activation of the downstream protein kinase A (PKA). We ask whether other neuromodulators are a

…that alter extracellular levels of norepinephrine (NE) and dopamine (DA), respectively. However, the dynamics of neurotransmitter release in these brain regions during stress has not been systematically explored. We used pharmacology and fiber photometric analysis to elucidate the impact of

The locus coeruleus (LC) is the primary source of norepinephrine in the brain and is known to modulate brain-wide arousal state. Recent evidence suggests that it also regulates immediate attentional responses by modulating the gain or reset of downstream cortical networks to optimize behavioral outcomes. Accordingly, cortical regions of high cognitive function, such as the medial prefrontal cortex (mPFC), are thought to directly influence LC output for this purpose. However, physiological evidence for monosynaptic connections between mPFC and LC neurons and their properties are still limited.

…striatum but their role, and that of norepinephrine (NE) as a potential striatal neuromodulator, is poorly understood. Given only a sparse norepinephrinergic input of the striatum but the dense innervation by DA, the endogen

…neuromodulators like cortisol and norepinephrine which may in turn affect foraging.Method:To this end, we collected data from 55 participants who played the virtual patch foraging game (Ba

An animal’s ability to evaluate environmental threats and mount an appropriate behavioral response is critical to survival. Based on previous literature in rodents and humans, we developed a novel rodent fear of heights task which is highly controllable and can be used to interrogate neural computations underlying innate threat processing. We developed a virtual height threat task in which animals are placed on a pole and must choose to exit to either a “close” or “far” virtual platform. We find that animals perform around chance levels when the discrepancy between visual stimuli is small (5cm

Norepinephrine (NE) is a neuromodulator that is released from projections of the locus coeruleus via extra-synaptic vesicle exocytosis (Fuxe, Borroto-Escuela, front. Physiol 2012). Previously, NE in the prefrontal cortex (PFC) was thought to be a homogenous field created by bulk release, but it remains unknown whether phasic (fast, short-term) fluctuations in NE can produce a spatially heterogeneous field, which could then structure cell firing at a fine spatial scale. To understand how spatiotemporal dynamics of NE release in the PFC affect neuronal firing, we performed a novel in-vivo two-ph

…Norepinephrine (NE) is released by surprise and uncertainty, and causal manipulations demonstrate a role for NE in threat learning. Thus, we hypothesized that NE encodes a threat prediction error signal, and compared NE release measurements in mice undergoing threat learning with predictions of TD learning. NE release scales with the strength of fear associations and threat imminence. Ho

To survive, animals must respond appropriately to changing external conditions. To do so quickly, animals use their past experiences to inform future actions. However, how past experience modulate information processing which ultimately influence behavior is still not well understood. Here we addressed this question by investigating how larval zebrafish use past action-outcome relationships to influence future responses to stimuli at the perceptual and behavioral levels. Fish were first made to adapt to changing locomotor efficacy, the difficulty of translating oneself through space. Fish inc

With the rapid growth of optical imaging technologies, the simultaneous observation of brain-wide activity and behavior in small organisms offers a unique opportunity to study how distributed neuronal networks interact to process sensory information and generate behavior. While neuromodulators have been shown to grant flexible state-switching mechanisms to circuits, their influence on global network dynamics is poorly characterized. Using resonant-scanning two-photon microscopy, we measured brain-wide calcium dynamics in head-restrained larval zebrafish while monitoring tail movements to inves

…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.

…that release the neurotransmitter norepinephrine (NE) throughout the brain. NE release may drive behavioral flexibility by facilitating the reorganization of neural activity in target brain areas, including the OFC. To test this hypothesis, mice were assessed in a T-maze reversal learning task, which requires subjects to reverse a previo

…catecholamine system, in particular, norepinephrine (NE) and dopamine (DA). Although both molecules have been implicated in decision making, their contributions have not been directly compared. When each neuromodulatory system is examined in isolation, they have been assigned similar roles in the latent cognitive processes that

The locus coeruleus (LC) serves as the primary source of the neuromodulator, norepinephrine (NE), in the brain. Through a widely divergent set of projections, LC neurons have been suggested 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