Progression of activity and structural changes in the anterior cingulate cortex during remote memory formation

Background Anesthetics aim to prevent memory of unpleasant experiences. The amygdala and dorsal anterior cingulate cortex participate in forging emotional and valence-driven memory formation. It was hypothesized that this circuitry maintains its role under sedation. Methods Two nonhuman primates underwent aversive tone–odor conditioning under sedative states induced by ketamine or midazolam (1 to 8 and 0.1 to 0.8 mg/kg, respectively). The primary outcome was behavioral and neural evidence suggesting memory formation. This study simultaneously measured conditioned inspiratory changes and changes in firing rate of single neurons in the amygdala and the dorsal anterior cingulate cortex in response to an expected aversive olfactory stimulus appearing during acquisition and tested their retention after recovery. Results Aversive memory formation occurred in 26 of 59 sessions under anesthetics (16 of 29 and 10 of 30, 5 of 30 and 21 of 29 for midazolam and ketamine at low and high doses, respectively). Single-neuron responses in the amygdala and dorsal anterior cingulate cortex were positively correlated between acquisition and retention (amygdala, n = 101, r = 0.51, P < 0.001; dorsal anterior cingulate cortex, n = 121, r = 0.32, P < 0.001). Neural responses during acquisition under anesthetics were stronger in sessions exhibiting memory formation than those that did not (amygdala median response ratio, 0.52 versus 0.33, n = 101, P = 0.021; dorsal anterior cingulate cortex median response ratio, 0.48 versus 0.32, n = 121, P = 0.012). The change in firing rate of amygdala neurons during acquisition was correlated with the size of stimuli-conditioned inspiratory response during retention (n = 101, r = 0.22 P = 0.026). Thus, amygdala and dorsal anterior cingulate cortex responses during acquisition under anesthetics predicted retention. Respiratory unconditioned responses to the aversive odor anesthetics did not differ from saline controls. Conclusions These results suggest that the amygdala–dorsal anterior cingulate cortex circuit maintains its role in acquisition and maintenance of aversive memories in nonhuman primates under sedation with ketamine and midazolam and that the stimulus valence is sufficient to drive memory formation. Editor’s Perspective What We Already Know about This Topic What This Article Tells Us That Is New

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Reduced anterior cingulate cortex volume induced by chronic stress correlates with increased behavioral emotionality and decreased synaptic puncta density

10.1101/2020.08.31.275750 ◽

2020 ◽

Author(s):

Keith A. Misquitta ◽

Amy Miles ◽

Thomas D. Prevot ◽

Jaime K. Knoch ◽

Corey Fee ◽

...

Keyword(s):

Nucleus Accumbens ◽

Anterior Cingulate Cortex ◽

Chronic Stress ◽

Restraint Stress ◽

Structural Changes ◽

Cingulate Cortex ◽

Anterior Cingulate ◽

List Type ◽

Chronic Restraint Stress ◽

Structural Covariance

AbstractClinical and preclinical studies report that chronic stress induces behavioral deficits as well as volumetric changes and synaptic alterations in corticolimbic brain regions including the anterior cingulate cortex (ACC), amygdala (AMY), nucleus accumbens (NAc) and hippocampus (HPC). In this study, we aimed to investigate the structural changes associated with chronic restraint stress (CRS) exposure and determine the relation between these volumetric changes with behavioral and synaptic alterations. Mice exposed to 2 and 5 weeks of CRS exhibited a significant increase in behavioral emotionality. Macrostructural changes assessed via MRI identified a negative CRS effect on total brain volume, proportional to behavioral emotionality. Region-specific changes within corticolimbic brain structures identified that only the ACC showed significant decrease in volume following CRS exposure (p<0.05). Reduced ACC correlated with increased behavioral emotionality (r=−0.50; p=0.002). Although not significantly altered by CRS, AMY and NAc (but not the HPC) volumes were negatively correlated with behavioral emotionality. Structural covariance network analysis revealed progressive decreased ACC degree following CRS exposure. Finally, reduced ACC volume correlated with decreased PSD95 (but not VGLUT1) puncta density (r=0.35, p<0.05), which also correlated with increased behavioral emotionality (r=−0.36, p<0.05), together suggesting that altered synaptic strength is an underlying substrate of the volumetric and behavioral effects of CRS Our results demonstrate that chronic stress effects on ACC volume and synaptic density are linked to the expression of depressive-like deficits. Our findings highlight key structural and morphological alterations in the ACC relevant to stress-related illness including mood and anxiety disorders.HighlightsChronic restraint stress induces decreases in anterior cingulate volume at 2 and 5 weeks following stress exposureVolume of the anterior cingulate cortex, amygdala and nucleus accumbens negatively correlate with behavioral emotionalityChronic stress induces a progressive decrease in strength and degree in structural covariance network connectivity of the anterior cingulate cortexPuncta density in the anterior cingulate cortex of post-synaptic marker PSD95 negatively correlates with behavioral emotionality and positively correlates with anterior cingulate cortex volume.

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Altered Posterior Cerebellar Lobule Connectivity With Perigenual Anterior Cingulate Cortex in Women With Primary Dysmenorrhea

Frontiers in Neurology ◽

10.3389/fneur.2021.645616 ◽

2021 ◽

Vol 12 ◽

Author(s):

Xiaoyan Wu ◽

Wenjun Yu ◽

Xuwei Tian ◽

Zhiying Liang ◽

Yun Su ◽

...

Keyword(s):

Functional Connectivity ◽

Anterior Cingulate Cortex ◽

Structural Changes ◽

Clinical Information ◽

Cingulate Cortex ◽

Anterior Cingulate ◽

Healthy Controls ◽

Primary Dysmenorrhea ◽

Voxel Based Morphometry ◽

Healthy Females

Objectives: This study aimed to investigate the potential connectivity mechanism between the cerebellum and anterior cingulate cortex (ACC) and the cerebellar structure in primary dysmenorrhea (PDM).Methods: We applied the spatially unbiased infratentorial template (SUIT) of the cerebellum to obtain anatomical details of cerebellar lobules, upon which the functional connectivity (FC) between the cerebellar lobules and ACC subregions was analyzed and the gray matter (GM) volume of cerebellar lobules was measured by using voxel-based morphometry (VBM) in 35 PDM females and 38 age-matched healthy females. The potential relationship between the altered FC or GM volume and clinical information was also evaluated in PDM females.Results: PDM females showed higher connectivity between the left perigenual ACC (pACC) and lobule vermis_VI, between the left pACC and left lobule IX, and between right pACC and right cerebellar lobule VIIb than did the healthy controls. Compared with healthy controls, no altered GM volume was found in PDM females. No significant correlation was found between altered cerebellum–ACC FC and the clinical variables in the PDM females.Conclusion: PDM females have abnormal posterior cerebellar connectivity with pACC but no abnormal structural changes. ACC–cerebellar circuit disturbances might be involved in the PDM females.

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