Noradrenaline

Noradrenaline (NA) is a ubiquitous neuromodulator largely produced by locus coeruleus (LC) neurons that impacts multiple cognitive processes. Non-invasive methods are used to track LC-NA activity. For instance, pupillometry is shown to be linked to arousal state, LC-NA, and other neuromodulator activity. However, given that pupillometry is a relatively slow process, the extent by which LC-NA can be predicted by pupil is limited. Since movements are linked with increased LC activity, orofacial movements could potentially be used as an additional psychophysiological marker for arousal and LC-N

Neuromodulation by the locus coeruleus (LC) plays a crucial role in cognitive processes related to learning, as well as memory consolidation (DOI: 10.1038/s41583-020-0360-9). Less is known about its role in memory retrieval. In this study, we explored this aspect following training of adult rats over a period of multiple days in an 8-arm radial maze to achieve robust spatial working memory (WM) and reference memory (RM) of the task. We then examined the consequence of patterned electrophysiological activation of the LC on the retrieval of recent (24h after the conclusion of training) or remote

Rebound depolarization (RD) is a form of membrane depolarization triggered in some neurons following hyperpolarization. Typically, a series of action potentials are evoked during RD plateau. RD converts an inhibitory signal arriving to the neuron into an excitation signal, which is subsequently synaptically transmitted to other cells. The nature of RD in cortical neurons has been tested for several years without satisfactory explanation. The aim of our study was to evaluate the influence of adrenergic receptors activation in RD generation. Alpha-1, alpha-2, and beta-receptors have been tested.

Noradrenaline is released via volume transmission from axons originating in the locus coeruleus and released into the parenchyma to be detected by both neurons and astrocytes. Noradrenergic α-1 receptors are Gq-coupled receptors that induce intracellular calcium release from the endoplasmic reticulum as a key pathway for astrocyte calcium signalling. Due to interactions between astrocytes and synapses including their known roles in structural isolation of synapses, metabolic support, potassium buffering and gliotransmitter release, fluctuations of intracellular calcium in astrocytes can influe

Neuromodulators such as monoamines or neuropeptides play crucial roles in modulating diverse brain functions. They can be released phasically, i.e. in response to stimuli, or tonically, in a spontaneous and more discrete manner. Understanding how these spontaneous releases occur is challenging yet essential, as their disruption is associated with behavioral and psychiatric disorders. A paradigm shift in this domain has been the generation of fluorescent probes sensitive enough to detect, using 2-photons microscopy, discrete tonic release of specific neuromodulators including dopamine, noradren

The brainstem locus coeruleus (LC) is the sole source of noradrenaline in the neocortex, hippocampus and cerebellum. Noradrenaline (NA) is a neuromodulator involved in the regulation of excitability of brain networks. In this study, we investigated whether chemogenetic activation of the LC is able to induce hippocampal noradrenaline release and affects hippocampal excitability.Male Sprague Dawley rats (n=8) were injected with the viral vector CAV2-PRSx8-hM3Dq in the LC for expression of hM3Dq, which allows chemogenetic LC activation upon systemic injection with deschloroclozapine (DCZ). Rats w

Noradrenaline (NA) is a strong modulator of neuronal activity and many autism spectrum disorder (ASD) symptoms can be attributed to maladaptive activity of locus coeruleus (LC), the main source of forebrain NA. Our lab recently uncovered a role for dysregulated LC-NA function in motor learning delays of the 16p11.2 deletion (+/-) mouse-model of ASD. We found that reduced NA levels in primary motor cortex (M1) caused delays in motor learning and increased neuronal activity in M1 pyramidal neurons. Both behavioral and neuronal phenotypes were rescued by chemogenetic activation of LC-NA. We next

Neuromodulatory systems, more specifically dopamine, noradrenaline, serotonin, and acetylcholine can dynamically change brain states and rapidly alter information processing of large number of neurons. Therefore, they can play a crucial role in cognitive functions, including learning and memory, and are accordingly severely implicated in neurodegenerative diseases. Interestingly, neuromodulatory systems often regulate seemingly overlapping cognitive processes and show similar modes of action. To reveal possible synergistic or antagonistic relations and to better understand the exact role of th

…CRF2 antagonist) on the release of noradrenaline (NA) in the locus coeruleus (LC) and serotonin (5HT3) in the raphe nuclei (RN). For this purpose, male Wistar rats were used, t

…The LC generates large noradrenaline (NA) signals that are key for the architecture of sleep in mice. In contrast, how LC malfunctions relate to sleep disturbances in AD remains unknown.We explore the real-time functionality of the noradrenergic system during AD’s prodromal phase in an established A

…Although monoamines such as noradrenaline (NE) and dopamine (DA) are key neuromodulators implicated in these cognitive functions, the modus operandi of monoaminergic systems and their relevance to cerebellar functioning remains poorly understood. Interestingly, we found that while in this brain region monoaminergic innervations are sparse, the main vesicular transpo

…novelty induces dopamine and noradrenaline release in the hippocampus which similarly enhances memories (Moncada et al., 2011; Duszkiewicz et al., 2019). However, the synaptic and molecular changes induced by novelty

…the locus coeruleus releases noradrenaline, a candidate for modulating synaptic plasticity within the PER. We explored the hypothesis that noradrenaline could transiently increase the excitability of the PER network, enhancing information transfer toward the hippocampus and ultimately leading to

Octopamine, the invertebrate analog of noradrenaline, induces locomotor activity in many invertebrate species. The position and structure of octopamine-synthesising neurons in the brain and ventral nerve cord of larval Drosophila have been documented using the expression patterns of tyrosine decarboxylase (TDC2+). Previous work documents that the larval locomotor network is composed of multiple rhythm generating networks that compete for dominance, with headsweep rhythm generators opposing forward rhythm generators. The role octopamine and TDC2+ neurons play in acute modulation and selection o

The brainstem locus coeruleus (LC) is a major source of noradrenaline to the forebrain and plays important roles in emotional learning. Though the LC receives synaptic inputs from the medial prefrontal cortex, a brain region important in cognitive and emotional processing, it is unclear whether and how prefrontal regions influence the LC particularly during fear extinction learning. To address this question, we first examined the detailed anatomical connectivity from prefrontal subregions to the LC in rats. Retrograde and anterograde tracing experiments showed that LC noradrenergic neurons rec

Arousal state has a major impact on perceptual ability, task performance, and diverse aspects of physiology and behavior. During wakefulness, spontaneous fluctuations in arousal state strongly modulate neural activity in numerous brain regions in mice, but the lack of large-scale, deep imaging methods has prevented testing whether these fluctuations affect the entire brain uniformly. Moreover, it remains unclear whether spontaneous and sensory-evoked fluctuations in arousal state engage the same brain circuits or are fundamentally distinct processes. To address this gap, we used functional ult

The Locus coeruleus (LC), the main noradrenaline-producing nucleus in the brain, is affected in a wide range of neurological conditions such as Parkinson's disease and Alzheimer's disease. Notably, the locus coeruleus-noradrenergic (LC-NA) system can be a therapeutic target through Vagus Nerve Stimulation. Transcutaneous auricular Vagus Nerve Stimulation (taVNS), an alternative technique that stimulates the auricular branch of the vagus nerve, is being studied as it’s less invasive, yet the nuanced neurocircuitry linking this branch of the vagus and LC remains unelucidated, as does the optimal

…to test the hypothesis that bursts of noradrenaline from the locus coeruleus help to facilitate shifts in perception by increasing neural gain across the cortex and flattening the whole brain ‘energy landscape’. In line with our hypothesis, shifts in the perceptual interpretation of an ambiguous image were associated with peaks in pupil diameter – a correlate of adrenergic tone. We trained a recurrent neural network (RNN) to perform an analog

…forebrain with the primary source of noradrenaline (NA), a neuromodulator important for a range of core behavioral and physiological functions (Aston-Jones & Cohen, 2005; Martins & Froemke, 2015; Poe et al., 2020). While early theories described the LC as a homogeneous structure whose neurons release NA uniformly to broadly coordinate brain states, recent studies have begun to reveal that complex behavioral contexts can lead to engagement of specific subpopulations of LC neurons depending on their inputs, outputs,

The pupil provides a rich, non-invasive measure of the neural bases of perception and cognition, and has been of particular value in uncovering the role of arousal-linked neuromodulation, which alters cortical processing as well as pupil size. But pupil size is subject to a multitude of influences, which complicates unique interpretation. We measured pupils of observers experiencing perceptual multistability -- an ever-changing subjective percept in the face of unchanging but inconclusive sensory input. In separate conditions the endogenously generated perceptual changes were either task-relev

My research uses a range of methods to better understand how the brain’s natural chemicals control complex behaviours, thoughts and perceptions. I also have a particular fascination about the factors that determine the contents of an individual’s conscious experience. In this talk I will present work that sits at the intersection of these two research areas looking at the role of different neurotransmitter systems in driving changes in conscious state. Specifically, I will discuss a series of studies using ambiguous stimuli to explore the neuropharmacological processes that underly alternation

…neuromodulators such as acetylcholine, noradrenaline, and serotonin, often non-synaptically. The mechanisms that underlie the interaction between these “wireless” non-synaptic signals and the “wired” cortical circuit are not well understood. Furthermore, neuromodulatory signaling is traditionally conside