The contribution of periaqueductal gray in the regulation of physiological and pathological behaviors

Zhang, Hui; Zhu, Zhe; Ma, Wei-Xiang; Kong, Ling-Xi; Yuan, Ping-Chuan; Bu, Li-Fang; Han, Jun; Huang, Zhi-Li; Wang, Yi-Qun

doi:10.3389/fnins.2024.1380171

Cited by 4 publications

References 156 publications

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Behavioral and neural correlates of diverse conditioned fear responses in male and female rats

Mitchell,

Vincelette,

Tuberman

et al. 2024

Preprint

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Pavlovian fear conditioning is a widely used tool that models associative learning in rodents. For decades the field has used predominantly male rodents and focused on a sole conditioned fear response: freezing. However, recent work from our lab and others has identified darting as a female-biased conditioned response, characterized by an escape-like movement across a fear conditioning chamber. It is also accompanied by a behavioral phenotype: Darters reliably show decreased freezing compared to Non-darters and males and reach higher velocities in response to the foot shock (“shock response”). However, the relationship between shock response and conditioned darting is not known. This study investigated if this link is due to differences in general processing of aversive stimuli between Darters, Non-darters and males. Across a variety of modalities, including corticosterone measures, the acoustic startle test, and sensitivity to thermal pain, Darters were found not to be more reactive or sensitive to aversive stimuli, and, in some cases, they appear less reactive to Non-darters and males. Analyses of cFos activity in regions involved in pain and fear processing following fear conditioning identified discrete patterns of expression among Darters, Non-darters, and males exposed to low and high intensity foot shocks. The results from these studies further our understanding of the differences between Darters, Non-darters and males and highlight the importance of studying individual differences in fear conditioning as indicators of fear state.

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Behavioral and neural correlates of diverse conditioned fear responses in male and female rats

Mitchell,

Vincelette,

Tuberman

et al. 2024

Preprint

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Neural Dynamics of Tonic Cold Pain: A Novel Investigation of an In-Scanner Alternative to the Cold Pressor Test in Healthy Individuals

Medina,

Hughes

2024

Preprint

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The cold pressor task (CPT) is widely used to study tonic pain during acute and chronic conditions and is often as used as a conditioning stimulus to activate descending pain control systems. However, logistical challenges in magnetic resonance imaging (MRI) limit its application, hindering the understanding of CPT's neural dynamics. To address this, we acquired resting-state functional MRI data from 30 healthy participants before, during, and after immersion in gelled-cold water, the closest in-scanner alternative to date to CPT for prolonged stimulation. Participants provided subjective pain intensity ratings after each scan, as well as average pain perceived during noxious stimulation, using a numeric rating scale (NRS). Following fMRI, participants rated their pain continuously during identical tonic noxious stimulation of the contralateral hand using a visual analogue scale (VAS). We employed three complementary methods to examine changes in brain function across fMRI conditions: a data-driven approach via independent component analysis (ICA), seed-to-whole-brain connectivity analysis with the periaqueductal grey (PAG) as seed, and spectral dynamic causal modelling (spDCM) to explore effective connectivity changes across the dorsal anterior cingulate cortex (dACC), anterior insulae (AI), thalamus, and PAG. NRS scores were significantly higher following tonic cold compared to baseline and recovery conditions. Continuous VAS reflected sustained mild-to-moderate pain over six minutes, with average VAS scores not significantly differing from NRS ratings recorded in the scanner. ICA identified engagement of descending pain control and sensorimotor networks during pain, with the latter persisting during recovery. Seed-based analysis revealed a disengagement between the PAG and cortical/subcortical regions involved in pain processing, such as the dACC, midcingulate cortex, AI, intraparietal sulcus, and precuneus. Finally, spDCM revealed tonic pain neural signature was most likely characterised by top-down inhibitory and bottom-up excitatory connections. This study establishes the cold gelled-water paradigm as a robust in-scanner alternative to CPT. By uncovering key neural dynamics of CPT, we provide new insights into the brain and brainstem mechanisms of tonic cold pain paradigms routinely used in psychophysical pain studies.

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Gamma-aminobutyric acid and glutamate/glutamine levels in the dentate nucleus and periaqueductal gray in new daily persistent headache: a magnetic resonance spectroscopy study

Chen,

Bai,

Wang

et al. 2024

J Headache Pain

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The contribution of periaqueductal gray in the regulation of physiological and pathological behaviors

Cited by 4 publications

References 156 publications

Behavioral and neural correlates of diverse conditioned fear responses in male and female rats

Behavioral and neural correlates of diverse conditioned fear responses in male and female rats

Neural Dynamics of Tonic Cold Pain: A Novel Investigation of an In-Scanner Alternative to the Cold Pressor Test in Healthy Individuals

Gamma-aminobutyric acid and glutamate/glutamine levels in the dentate nucleus and periaqueductal gray in new daily persistent headache: a magnetic resonance spectroscopy study

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