Noradrenaline release from the locus coeruleus shapes stress-induced hippocampal gene expression DOI Creative Commons
Mattia Privitera, Lukas von Ziegler, Amalia Floriou‐Servou

et al.

eLife, Journal Year: 2023, Volume and Issue: 12

Published: Aug. 1, 2023

Exposure to an acute stressor triggers a complex cascade of neurochemical events in the brain. However, deciphering their individual impact on stress-induced molecular changes remains major challenge. Here, we combine RNA sequencing with selective pharmacological, chemogenetic, and optogenetic manipulations isolate contribution locus coeruleus-noradrenaline (LC-NA) system stress response mice. We reveal that NA release during exposure regulates large reproducible set genes dorsal ventral hippocampus via β-adrenergic receptors. For smaller subset these genes, show triggered by LC stimulation is sufficient mimic transcriptional response. observe effects both sexes, independent pattern frequency activation. Using retrograde approach, demonstrate hippocampus-projecting neurons directly regulate hippocampal gene expression. Overall, highly astrocyte-enriched emerges as key targets LC-NA activation, most prominently several subunits protein phosphatase 1 (Ppp1r3c, Ppp1r3d, Ppp1r3g) type II iodothyronine deiodinase (Dio2). These results highlight importance astrocytic energy metabolism thyroid hormone signaling LC-mediated function offer new for understanding how impacts brain health disease.

Language: Английский

Lights, fiber, action! A primer on in vivo fiber photometry DOI Creative Commons
Eleanor H. Simpson, Thomas Akam, Tommaso Patriarchi

et al.

Neuron, Journal Year: 2023, Volume and Issue: 112(5), P. 718 - 739

Published: Dec. 15, 2023

Fiber photometry is a key technique for characterizing brain-behavior relationships in vivo. Initially, it was primarily used to report calcium dynamics as proxy neural activity via genetically encoded indicators. This generated new insights into brain functions including movement, memory, and motivation at the level of defined circuits cell types. Recently, opportunity discovery with fiber has exploded development an extensive range fluorescent sensors biomolecules neuromodulators peptides that were previously inaccessible critical advance, combined availability affordable "plug-and-play" recording systems, made monitoring molecules high spatiotemporal precision during behavior highly accessible. However, while opening exciting avenues research, rapid expansion applications occurred without coordination or consensus on best practices. Here, we provide comprehensive guide help end-users execute, analyze, suitably interpret studies.

Language: Английский

Citations

51

Distinct neurochemical influences on fMRI response polarity in the striatum DOI Creative Commons
Domenic H. Cerri, Daniel L. Albaugh, Lindsay R. Walton

et al.

Nature Communications, Journal Year: 2024, Volume and Issue: 15(1)

Published: March 1, 2024

Abstract The striatum, known as the input nucleus of basal ganglia, is extensively studied for its diverse behavioral roles. However, relationship between neuronal and vascular activity, vital interpreting functional magnetic resonance imaging (fMRI) signals, has not received comprehensive examination within striatum. Here, we demonstrate that optogenetic stimulation dorsal striatal neurons or their afferents from various cortical subcortical regions induces negative fMRI responses in rats, manifesting vasoconstriction. These occur even with heightened confirmed by electrophysiology fiber-photometry. In parallel, midbrain dopaminergic neuron modulation, coupled electrochemical measurements, establishes a link vasodilation dopamine release. Intriguingly, vivo intra-striatal pharmacological manipulations during highlight critical role opioidergic signaling generating This observation substantiated detecting vasoconstriction brain slices after synthetic opioid application. humans, aimed at increasing activity likewise elicit responses. Our results emphasize necessity considering vasoactive neurotransmission alongside when signal.

Language: Английский

Citations

17

Brain-heart interactions in the neurobiology of consciousness DOI Creative Commons
Diego Candia‐Rivera

Current Research in Neurobiology, Journal Year: 2022, Volume and Issue: 3, P. 100050 - 100050

Published: Jan. 1, 2022

Recent experimental evidence on patients with disorders of consciousness revealed that observing brain-heart interactions helps to detect residual consciousness, even in absence behavioral signs consciousness. Those findings support hypotheses suggesting visceral activity is involved the neurobiology and sum existing healthy participants which neural responses heartbeats reveal perceptual self-consciousness. More obtained through mathematical modeling physiological dynamics emotion processing prompted by an initial modulation from ascending vagal inputs brain, followed sustained bidirectional interactions. long-lasting causal role bodily emotions, feelings, potentially In this paper, theoretical landscape potential cognition reviewed, as well supporting these hypotheses. I advocate for methodological developments estimation uncover cardiac origin, levels, contents The ongoing depicts further than cortical evoked each heartbeat, presence non-linear, complex, communication between brain heartbeat dynamics. Further methodologies analyze may contribute a better understanding homeostatic-allostatic control, cognitive functions,

Language: Английский

Citations

56

Noradrenergic and cholinergic systems take centre stage in neuropsychiatric diseases of ageing DOI Creative Commons
Isabella F. Orlando, James M. Shine, Trevor W. Robbins

et al.

Neuroscience & Biobehavioral Reviews, Journal Year: 2023, Volume and Issue: 149, P. 105167 - 105167

Published: April 11, 2023

Noradrenergic and cholinergic systems are among the most vulnerable brain in neuropsychiatric diseases of ageing, including Alzheimer's disease, Parkinson's Lewy body dementia, progressive supranuclear palsy. As these fail, they contribute directly to many characteristic cognitive psychiatric symptoms. However, their contribution symptoms is not sufficiently understood, pharmacological interventions targeting noradrenergic have met with mixed success. Part challenge complex neurobiology systems, operating across multiple timescales, non-linear changes adult lifespan disease course. We address challenges a detailed review outlining roles cognition behaviour, how influence disease. By bridging levels analysis, we highlight opportunities for improving drug therapies pursuing personalised medicine strategies.

Language: Английский

Citations

33

Optogenetic stimulation of anterior insular cortex neurons in male rats reveals causal mechanisms underlying suppression of the default mode network by the salience network DOI Creative Commons
Vinod Menon, Domenic H. Cerri, Byeongwook Lee

et al.

Nature Communications, Journal Year: 2023, Volume and Issue: 14(1)

Published: Feb. 16, 2023

Abstract The salience network (SN) and default mode (DMN) play a crucial role in cognitive function. SN, anchored the anterior insular cortex (AI), has been hypothesized to modulate DMN activity during stimulus-driven cognition. However, causal neural mechanisms underlying changes its functional connectivity with SN are poorly understood. Here we combine feedforward optogenetic stimulation fMRI computational modeling dissect of AI neurons dynamic interactions between nodes male rat brain. Optogenetic Chronos-expressing suppressed activity, decreased AI-DMN intra-DMN connectivity. Our findings demonstrate that induces suppression decoupling elucidates previously unknown features rodent brain organization. study advances foundational knowledge cross-network switching.

Language: Английский

Citations

31

Neuronal dynamics of the default mode network and anterior insular cortex: Intrinsic properties and modulation by salient stimuli DOI Creative Commons
Tzu-Hao Harry Chao, Byeongwook Lee, Li‐Ming Hsu

et al.

Science Advances, Journal Year: 2023, Volume and Issue: 9(7)

Published: Feb. 15, 2023

The default mode network (DMN) is critical for self-referential mental processes, and its dysfunction implicated in many neuropsychiatric disorders. However, the neurophysiological properties task-based functional organization of rodent DMN are poorly understood, limiting translational utility. Here, we combine fiber photometry with magnetic resonance imaging (fMRI) computational modeling to characterize dynamics putative rat nodes their interactions anterior insular cortex (AI) salience network. Our analysis revealed neuronal activity changes AI preceding fMRI-derived activations cyclical transitions between brain states. Furthermore, demonstrate that salient oddball stimuli suppress enhance causally inhibits retrosplenial cortex, a prominent node. These findings elucidate foundations DMN, spatiotemporal dynamical properties, modulation by stimuli, paving way future studies.

Language: Английский

Citations

30

Mapping and comparing fMRI connectivity networks across species DOI Creative Commons
Marco Pagani, Daniel Gutierrez‐Barragan, A. Elizabeth de Guzman

et al.

Communications Biology, Journal Year: 2023, Volume and Issue: 6(1)

Published: Dec. 7, 2023

Abstract Technical advances in neuroimaging, notably fMRI, have allowed distributed patterns of functional connectivity to be mapped the human brain with increasing spatiotemporal resolution. Recent years seen a growing interest extending this approach rodents and non-human primates understand mechanism fMRI complement investigations connectome. Here, we discuss current challenges opportunities mapping across species. We underscore critical importance physiologically decoding neuroimaging measures (dys)connectivity via multiscale mechanistic animals. next highlight set general principles governing organization mammalian networks These include presence evolutionarily conserved network systems, dominant cortical axis connectivity, common repertoire topographically modes. finally describe emerging approaches allowing comparisons extrapolations findings As neuroscientists gain access increasingly sophisticated perturbational, computational recording tools, cross-species offers novel investigate large-scale health disease.

Language: Английский

Citations

25

Impaired value-based decision-making in Parkinson’s disease apathy DOI Creative Commons

William Gilmour,

Graeme Mackenzie,

Mathias Feile

et al.

Brain, Journal Year: 2024, Volume and Issue: 147(4), P. 1362 - 1376

Published: Feb. 2, 2024

Abstract Apathy is a common and disabling complication of Parkinson’s disease characterized by reduced goal-directed behaviour. Several studies have reported dysfunction within prefrontal cortical regions projections from brainstem nuclei whose neuromodulators include dopamine, serotonin noradrenaline. Work in animal human neuroscience confirmed contributions these on aspects motivated decision-making. Specifically, overlapping to encoding the value decisions, influence whether explore alternative courses action or persist an existing strategy achieve rewarding goal. Building upon this work, we hypothesized that apathy should be associated with impairment value-based learning. Using four-armed restless bandit reinforcement learning task, studied decision-making 75 volunteers; 53 patients disease, without clinical apathy, 22 age-matched healthy control subjects. Patients exhibited impaired ability choose highest bandit. Task performance predicted individual patient’s severity measured using Lille Rating Scale (R = −0.46, P < 0.001). Computational modelling choices group made decisions were indifferent learnt options, consistent previous reports reward insensitivity. Further analysis demonstrated shift away exploiting option reduction perseveration, which also correlated scores −0.5, We went acquire functional MRI 59 19 20 controls performing Restless Bandit Task. Analysis signal at point feedback diminished ventromedial cortex was more marked but not predictive their severity. model-based categorization choice type, lower bandits activated similar degree controls. In contrast, significantly increased activation across distributed thalamo-cortical network. Enhanced activity thalamus both patient groups connectivity dorsal anterior cingulate insula. Given task no different subjects, interpret recruitment network as possible compensatory mechanism, compensates against symptomatic manifestation disease.

Language: Английский

Citations

9

Disruption of locus coeruleus-related functional networks in Parkinson’s disease DOI Creative Commons
Junyan Sun, Jinghong Ma, Linlin Gao

et al.

npj Parkinson s Disease, Journal Year: 2023, Volume and Issue: 9(1)

Published: May 30, 2023

Locus coeruleus (LC) is severely affected in Parkinson's Disease (PD). However, alterations LC-related resting-state networks (RSNs) PD remain unclear. We used functional MRI to investigate the connectivity (FC) of RSNs and associations between changes clinical features idiopathic rapid eye movement sleep behavior disorder (iRBD) patients with (PDRBD+) without RBD (PDRBD-). There was a similarly disrupted FC pattern iRBD PDRBD+ patients, whereas were less damaged PDRBD- than that PDRBD+. The correlated cognition duration iRBD, depression PDRBD-, severity Our findings demonstrate are significantly prodromal stage α-synucleinopathies proposed body-first (PDRBD+), but brain-first

Language: Английский

Citations

17

Racial Discrimination, Neural Connectivity, and Epigenetic Aging Among Black Women DOI Creative Commons
Aziz Elbasheir, Şeyma Katrinli, Breanne E. Kearney

et al.

JAMA Network Open, Journal Year: 2024, Volume and Issue: 7(6), P. e2416588 - e2416588

Published: June 13, 2024

Racial discrimination increases the risk of adverse brain health outcomes, potentially via neuroplastic changes in emotion processing networks. The involvement deep regions (brainstem and midbrain) these responses is unknown. Potential associations racial with alterations functional connectivity accelerated epigenetic aging, a process that substantially vulnerability to problems, are also

Language: Английский

Citations

7