Spatiotemporal dynamics of noradrenaline during learned behaviour

Breton-Provencher, Vincent; Drummond, Gabrielle T.; Feng, Jiguang; Li, Yulong; Sur, Mriganka

doi:10.1038/s41586-022-04782-2

Cited by 82 publications

(96 citation statements)

References 66 publications

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“…Early recordings from the LC in awake, behaving rodents or monkeys revealed tonic increases in average firing rate related to arousal and phasic, often synchronous, discharge associated with short-term increases in behavioral vigilance to external environment and stimuli (reviewed in Aston-Jones and Cohen 2005; Sara and Bouret 2012; Sara 2009). More recent investigations reveal at least some degree of heterogeneity and specialization in LC neuronal signaling (see below; Poe et al 2020; Totah, Logothetis, and Eschenko 2019; Breton-Provencher et al 2022; Uematsu et al 2017; Chandler, Gao, and Waterhouse 2014). Our observation of a common signal across noradrenergic axons related to behavioral state (e.g.…”

Section: Discussionmentioning

confidence: 99%

“…In addition to a global behavioral state-linked signal, ACh and LC-NA may also provide heterogeneous signals throughout the brain. These targeted signals may support a range of brain processes and behaviors, including selective sensory processing, cortical plasticity, and memory formation (Janitzky et al 2015;Aston-Jones and Cohen 2005;Sara 2009;Sara and Bouret 2012;Usher 1999;Deitcher et al, 2019;Breton-Provencher et al 2022;Uematsu et al 2017;Polack, Friedman, and Golshani 2013;Pinto et al 2013;Nelson and Mooney 2016a;Goard and Dan 2009;Ego-Stengel et al 2001). Specificity of cholinergic cortical signaling has been demonstrated both anatomically and functionally.…”

Section: Heterogeneous Ach and Lc-na Signalingmentioning

confidence: 99%

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Cholinergic and noradrenergic axonal activity contains a behavioral-state signal that is coordinated across the dorsal cortex

Collins

Francis

Emanuel

et al. 2022

Preprint

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Fluctuations in brain and behavioral state are supported by broadly projecting neuromodulatory systems. In this study, we use mesoscale two-photon calcium imaging to examine spontaneous activity of cholinergic and noradrenergic axons in awake mice, in order to determine the interaction between arousal/movement state transitions and neuromodulatory activity across the dorsal cortex at distances separated by up to 4 mm. We confirm that GCaMP6s activity within axonal projections of both basal forebrain cholinergic and locus coeruleus noradrenergic neurons track arousal, indexed as pupil diameter, and changes in behavioral engagement, as reflected by bouts of whisker movement and/or locomotion. The broad coordination in activity between even distant axonal segments indicates that both of these systems can operate in a global fashion, especially in relation to changes in behavioral state. In addition to this broadly coordinated activity, we also find that a subpopulation of both cholinergic and noradrenergic axons exhibit heterogeneity in activity that appears to be independent of our measures of behavioral state. By monitoring the activity of cholinergic interneurons in the cortex we found that a subpopulation of these cells exhibit state-dependent (arousal/movement) activity. These results demonstrate that cholinergic and noradrenergic systems not only provide a prominent and broadly synchronized signal related to behavioral state, but may also provide more heterogeneous activity independent of this general signal. Together, these two systems may prepare the cortex for both broad behavioral state transitions as well as regionally or temporally specific cortical dynamics.

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Section: Discussionmentioning

confidence: 99%

Section: Heterogeneous Ach and Lc-na Signalingmentioning

confidence: 99%

Cholinergic and noradrenergic axonal activity contains a behavioral-state signal that is coordinated across the dorsal cortex

Collins

Francis

Emanuel

et al. 2022

Preprint

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“…In particular, electrophysiological signatures have been observed for multiple outputs, and these may be liable to plasticity induced by experience (stressors) (Borodovitsyna et al, 2020; Chandler et al, 2014; Li et al, 2016). Moreover, there appear to be discrete modules that influence different motivated behaviors (Breton-Provencher et al, 2022; Hickey et al, 2014; Hirschberg et al, 2017). Future studies investigating how tau pathology and ethanol alter these individual modules would be undoubtedly insightful.…”

Section: Discussionmentioning

confidence: 99%

Tauopathy and alcohol consumption interact to alter locus coeruleus excitatory transmission and excitability in male and female mice

Downs¹,

Catavero

Kasten

et al. 2022

Preprint

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Alcohol use disorder is a major public health concern in the United States. Recent work has suggested a link between chronic alcohol consumption and the development of tauopathy disorders, such as Alzheimers Disease and Frontal-Temporal Dementia. However, relatively little work has investigated changes in neural circuitry involved in both tauopathy disorders and alcohol use disorder. The locus coeruleus (LC) is the major noradrenergic nuclei in the brain and is one of the earliest sites to be affected by tau lesions. The LC is also implicated in the rewarding effects of ethanol and alcohol withdrawal. In this study we assessed effects of long-term ethanol consumption and tauopathy on the physiology of LC neurons. Male and female P301S mice, a humanized transgenic mouse model of tauopathy, underwent 16 weeks of intermittent access to 20% ethanol from 3 to 7 months of age. We observed higher total alcohol consumption in female mice regardless of genotype. Male P301S mice consumed more ethanol and had a greater preference for ethanol than WT males. At the end of the drinking study, LC function was assessed using ex vivo whole cell electrophysiology. We found significant changes in excitatory inputs to the LC due to both ethanol and genotype. We found significantly increased excitability of the LC due to ethanol with greater effects in female P301S mice than WT. Our study identifies significant changes in the LC due to interactions between tauopathy and long-term ethanol use. These findings could have important implications regarding LC activity and changes in behavior due to both ethanol and tauopathy related dementia.

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“…In addition, there are theoretical reasons to believe that the finite nature of biological networks may imbue specific limits on the number of possible tasks that can be run in parallel, although we expect that the high-dimensional architecture of the cerebellum 11 will likely boost this capacity, particularly as a function of experience 26, 27 . Precisely which systems in the brain help to control this balance remains an open question, however there is intriguing results to suggest that the neuromodulatory system may play a crucial role in this process 26, 51, 52 .…”

Section: Discussionmentioning

confidence: 99%

Parallel processing relies on a distributed, low-dimensional cortico-cerebellar architecture

Müller

Hou

Palesi

et al. 2022

Preprint

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A characteristic feature of human cognition is our ability to 'multi-task' - performing two or more tasks in parallel - particularly when one task is well-learned. How the brain supports this capacity remains poorly understood. Most past studies have focussed on identifying the areas of the brain - typically the dorsolateral prefrontal cortex - that are required to navigate information processing bottlenecks. In contrast, we take a systems neuroscience approach to test the hypothesis that the capacity to conduct effective parallel processing relies on a distributed architecture that interconnects the cerebral cortex with the cerebellum. The latter structure contains over half of the neurons in the adult human brain, and is well-suited to support the fast, effective, dynamic sequences required to perform tasks relatively automatically. By delegating stereotyped within-task computations to the cerebellum, the cerebral cortex can be freed up to focus on the more challenging aspects of performing the tasks in parallel. To test this hypothesis, we analysed task-based fMRI data from 50 participants who performed a task in which they either balanced an avatar on a screen ('Balance'), performed serial-7 subtractions ('Calculation') or performed both in parallel ('Dual-Task'). Using a set of approaches that include dimensionality reduction, structure-function coupling and time-varying functional connectivity, we provide robust evidence in support of our hypothesis. We conclude that distributed interactions between the cerebral cortex and cerebellum are crucially involved in parallel processing in the human brain.

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Spatiotemporal dynamics of noradrenaline during learned behaviour

Cited by 82 publications

References 66 publications

Cholinergic and noradrenergic axonal activity contains a behavioral-state signal that is coordinated across the dorsal cortex

Cholinergic and noradrenergic axonal activity contains a behavioral-state signal that is coordinated across the dorsal cortex

Tauopathy and alcohol consumption interact to alter locus coeruleus excitatory transmission and excitability in male and female mice

Parallel processing relies on a distributed, low-dimensional cortico-cerebellar architecture

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