Retrorubral field is a hub for diverse threat and aversive outcome signals

Moaddab, Mahsa; McDannald, Michael A.

doi:10.1016/j.cub.2021.02.055

Cited by 14 publications

(12 citation statements)

References 100 publications

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“…For both 30 and 100 mg/kg treatment groups, we observed a robust decrease in the dorsal raphe (DR 37 ) and increase in the lateral hypothalamic region zona incerta (ZI 38 ). In addition, in the 100 mg/kg treatment group, we observed a robust decrease in the reticular nucleus retrorubral area (RR 39 ) and increases in the arcuate hypothalamic nucleus (ARH 40 ), the periventricular hypothalamic nucleus posterior part (PVp), tuberomammillary nucleus (TM) and the periventricular hypothalamic nucleus descending division (PVHd) (Fig. 3a).…”

Section: Dosage-dependent Divergent Impact Of Chronic Ketamine Exposu...mentioning

confidence: 86%

Whole-brain mapping reveals the divergent impact of ketamine on the dopamine system

Datta

Chen²,

Chauhan³

et al. 2023

Preprint

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Ketamine is a multifunctional drug with clinical applications as an anesthetic, as a pain management medication and as a transformative fast-acting antidepressant. It is also abused as a recreational drug due to its dissociative property. Recent studies in rodents are revealing the neuronal mechanisms that mediate the complex actions of ketamine, however, its long-term impact due to prolonged exposure remains much less understood with profound scientific and clinical implications. Here, we develop and utilize a high-resolution whole-brain phenotyping approach to show that repeated ketamine administration leads to a dosage-dependent decrease of dopamine (DA) neurons in the behavior state-related midbrain regions and, conversely, an increase within the hypothalamus. Congruently, we show divergently altered innervations of prefrontal cortex, striatum, and sensory areas. Further, we present supporting data for the post-transcriptional regulation of ketamine-induced structural plasticity. Overall, through an unbiased whole-brain analysis, we reveal the divergent brain-wide impact of chronic ketamine exposure on the association and sensory pathways.

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Section: Dosage-dependent Divergent Impact Of Chronic Ketamine Exposu...mentioning

confidence: 86%

Whole-brain mapping reveals the divergent impact of ketamine on the dopamine system

Datta

Chen²,

Chauhan³

et al. 2023

Preprint

View full text Add to dashboard Cite

show abstract

“…However, these nuclei are known to contain DAergic neurons (Bjorklund & Dunnett, 2007;Richards et al, 1997). Neurons in the SNpr and retrorubral field displayed either increased or decreased responses towards the CS+ during acquisition similar to the VTA and SNpc (Joshua et al, 2010;Moaddab et al, 2021). Furthermore, zona incerta DA neurons increase their activity towards CS+ during fear acquisition and recall (Zhang et al, 2022) and are involved in fear extinction (Venkataraman et al, 2021).…”

Section: Other Possible Nuclei and Subpopulationsmentioning

confidence: 99%

50 Years of Research on Dopamine’s Role in Passive Aversive Conditioning and Extinction: A Systematic Review

Hamati

Ahrens

Holahan

et al. 2023

Preprint

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Dopamine, a catecholamine neurotransmitter, has historically been associated with the encoding of reward, whereas its role in aversion has received less attention. Here, we systematically gather the vast evidence for a role of dopamine in the simplest form of aversive learning: passive aversive conditioning and extinction. In the past, crude methods were used to augment or inhibit dopamine in order to study its relationship with fear conditioning and extinction. More advanced techniques such as conditional genetic, chemogenic, and optogenetic approaches now provide causal evidence for dopamine’s role in these learning processes. Dopamine neurons encode fear and extinction-related information and convey the signal via activation of D1, D2, D3, and D4 receptor sites particularly in the amygdala, prefrontal cortex, and striatum in order to continuously form, consolidate, retrieve, and update fear and extinction memory in a dynamic and reciprocal manner. Based on the reviewed literature, we conclude that dopamine is crucial for the encoding of passive aversive conditioning and contributes in a way that is comparable to its role in encoding reward.

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“…However, evidence of widespread brainstem threat probability signaling remains elusive, and more complete descriptions of brainstem behavior and prediction error signaling are needed. Recording a 21-region axis with Neuropixels 10 during probabilistic fear discrimination 11 , we report the brainstem constructs signals for threat probability, fear behavior, and prediction error from neuronal “building blocks” organized into functional networks. Remapping of neuronal function between cue and outcome periods revealed distinct brainstem network organization for threat probability, fear behavior, and prediction error signaling.…”

Section: Introductionmentioning

confidence: 99%

Brainstem networks construct threat probability and prediction error from neuronal building blocks

Strickland

McDannald

2022

Nat Commun

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When faced with potential threat we must estimate its probability, respond advantageously, and leverage experience to update future estimates. Threat estimation is the proposed domain of the forebrain, while behaviour is elicited by the brainstem. Yet, the brainstem is also a source of prediction error, a learning signal to acquire and update threat estimates. Neuropixels probes allowed us to record single-unit activity across a 21-region brainstem axis in rats receiving probabilistic fear discrimination with foot shock outcome. Against a backdrop of diffuse behaviour signaling, a brainstem network with a dorsal hub signaled threat probability. Neuronal function remapping during the outcome period gave rise to brainstem networks signaling prediction error and shock on multiple timescales. The results reveal brainstem networks construct threat probability, behaviour, and prediction error signals from neuronal building blocks.

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Retrorubral field is a hub for diverse threat and aversive outcome signals

Cited by 14 publications

References 100 publications

Whole-brain mapping reveals the divergent impact of ketamine on the dopamine system

Whole-brain mapping reveals the divergent impact of ketamine on the dopamine system

50 Years of Research on Dopamine’s Role in Passive Aversive Conditioning and Extinction: A Systematic Review

Brainstem networks construct threat probability and prediction error from neuronal building blocks

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