Noradrenaline
noradrenaline
Dr. Melissa Caras
We are looking for a postdoctoral fellow to study neuromodulatory mechanisms supporting auditory perceptual learning in Mongolian gerbils. The successful applicant will measure and manipulate neuromodulatory release, and assess its impact on cortical activity in freely-moving animals engaged in auditory detection tasks. A variety of techniques will be used, including in vivo multichannel electrophysiology and pharmacology, fiber photometry, novel genetically-encoded fluorescent biosensors, chemogenetics and/or optogenetics. The candidate will be highly involved in all aspects of the research, from design to publication, and will additionally have the opportunity to mentor graduate and undergraduate students.
Separable pupillary signatures of perception and action during perceptual multistability
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-relevant or not, allowing a separation between perception-related and task-related pupil signals. Perceptual changes were marked by a complex pupil response that could be decomposed into two components: a dilation tied to task execution and plausibly indicative of an arousal-linked noradrenaline surge, and an overlapping constriction tied to the perceptual transient and plausibly a marker of altered visual cortical representation. Constriction, but not dilation, amplitude systematically depended on the time interval between perceptual changes, possibly providing an overt index of neural adaptation. These results show that the pupil provides a simultaneous reading on interacting but dissociable neural processes during perceptual multistability, and suggest that arousal-linked neuromodulation shapes action but not perception in these circumstances. This presentation covers work that was published in e-life
Context-Dependent Relationships between Locus Coeruleus Firing Patterns and Coordinated Neural Activity in the Anterior Cingulate Cortex
Ascending neuromodulatory projections from the locus coeruleus (LC) affect cortical neural networks via the release of norepinephrine (NE). However, the exact nature of these neuromodulatory effects on neural activity patterns in vivo is not well understood. Here we show that in awake monkeys, LC activation is associated with changes in coordinated activity patterns in the anterior cingulate cortex (ACC). These relationships, which are largely independent of changes in firing rates of individual ACC neurons, depend on the type of LC activation: ACC pairwise correlations tend to be reduced when tonic (baseline) LC activity increases but are enhanced when external events drive phasic LC responses. Both relationships covary with pupil changes that reflect LC activation and arousal. These results suggest that modulations of information processing that reflect changes in coordinated activity patterns in cortical networks can result partly from ongoing, context-dependent, arousal-related changes in activation of the LC-NE system.
The pharmacology of consciousness
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 alternations in perceptual awareness. By comparing different methods and neurotransmitter systems including: serotonin (psychedelics), noradrenaline (pupillometry) and Glutamate/GABA (Magnetic Resonance Spectroscopy MRS) we can start to tease apart the distinct role that different neurotransmitter systems play in coordinating conscious experience across time.
Circuit mechanisms underlying the dynamic control of cortical processing by subcortical neuromodulators
Behavioral states such as arousal and attention can have profound effects on sensory processing, determining how – sometimes whether – a stimulus is processed. This state-dependence is believed to arise, at least in part, as a result of inputs to cortex from subcortical structures that release 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 considered broad in its impact across cortex (within a species) and consistent in its form and function across species (at least in mammals). The work I will present approaches the challenge of understanding neuromodulatory action in the cortex from a number of angles: anatomy, physiology, pharmacology, and chemistry. The overarching goal of our effort is to elucidate the mechanisms behind local neuromodulation in the cortex of non-human primates, and to reveal differences in structure and function across cortical model systems.
Using a recurrent neural network to predict noradrenaline release by locus coeruleus neurons based on facial features in mice
COSYNE 2025
Astrocyte noradrenaline α-1A receptor activation induces changes to inhibitory synaptic transmission in the hippocampus and reduces the frequency of pharmacoresistant spontaneous seizures
FENS Forum 2024
Chemogenetic activation of the locus coeruleus increases hippocampal noradrenaline levels leading to modulation of hippocampal excitability
FENS Forum 2024
Chronic in vivo two-photon imaging of cortical noradrenaline reveals altered spatiotemporal release dynamics during motor learning in a mouse model of autism
FENS Forum 2024
The effects of CRF agonists and antagonists on the noradrenaline released from the locus coeruleus and the serotonin released from the raphe nuclei
FENS Forum 2024
Noradrenaline-mediated glial calcium wave: A physiological fuse evoking motor arrest
FENS Forum 2024
Prefrontal cortical subregions bidirectionally control fear extinction through projections to the brainstem noradrenaline system
FENS Forum 2024
The role of noradrenaline in medial forebrain bundle deep brain stimulation: A physiological and anatomical approach
FENS Forum 2024