OBJECTIVES: To investigate the mechanism by which the pyramidal neurons of the anterior cingulate cortex (ACC) modulate the effects of enriched environment (EE) for relieving anxiety-like behaviors in mice. METHODS: C57BL/6J mice were randomly divided into control group, restraint stress (RS) group, and RS+EE group (n=8). The mice in the latter two groups were subjected to RS for 2 h daily for 3 days, and those in RS+EE group were housed in an EE during modeling. Anxiety-like behaviors of the mice were evaluated using the elevated plus-maze tests (EPM) and open field test (OFT). Changes in c-Fos expression in the ACC of the mice were detected with immunofluorescence assay, and pyramidal neuron excitability in the ACC (Pyn^ACC) was measured using patch-clamp technique. The miniature excitatory and inhibitory postsynaptic currents (mEPSC and mIPSC, respectively) were analyzed to assess synaptic transmission changes. RESULTS: Behavioral tests showed obvious anxiety-like behaviors in RS mice, and such behavioral changes were significantly improved in RS+EE mice. Immunofluorescence staining revealed significantly increased c-Fos expression in the ACC in RS mice but lowered c-Fos expression in RS+EE group. Compared with the control mice, the RS mice showed increased action potential firing rate of Pyn^ACC, which was significantly reduced in RS+EE group. Compared with the RS mice, the RS+EE mice showed also decreased frequency of mEPSCs of Pyn^ACC, but the amplitude exhibited no significant changes. No obvious changes in the frequency or amplitude of mIPSCs were observed in RS+EE mice. CONCLUSIONS EE reduces excitability of Pyn^ACC to alleviate anxiety-like behaviors induced by RS in mice.
Animals ; Anxiety/physiopathology* ; Gyrus Cinguli ; Mice, Inbred C57BL ; Mice ; Pyramidal Cells/physiology* ; Restraint, Physical ; Stress, Psychological ; Proto-Oncogene Proteins c-fos/metabolism* ; Male ; Behavior, Animal ; Environment ; Excitatory Postsynaptic Potentials

Within the prefrontal-cingulate cortex, abnormalities in coupling between neuronal networks can disturb the emotion-cognition interactions, contributing to the development of mental disorders such as depression. Despite this understanding, the neural circuit mechanisms underlying this phenomenon remain elusive. In this study, we present a biophysical computational model encompassing three crucial regions, including the dorsolateral prefrontal cortex, subgenual anterior cingulate cortex, and ventromedial prefrontal cortex. The objective is to investigate the role of coupling relationships within the prefrontal-cingulate cortex networks in balancing emotions and cognitive processes. The numerical results confirm that coupled weights play a crucial role in the balance of emotional cognitive networks. Furthermore, our model predicts the pathogenic mechanism of depression resulting from abnormalities in the subgenual cortex, and network functionality was restored through intervention in the dorsolateral prefrontal cortex. This study utilizes computational modeling techniques to provide an insight explanation for the diagnosis and treatment of depression.
Prefrontal Cortex/physiology* ; Humans ; Emotions/physiology* ; Cognition/physiology* ; Gyrus Cinguli/physiology* ; Computer Simulation ; Models, Neurological ; Neural Pathways/physiology* ; Nerve Net/physiology*

In this study, we investigated how empathic neural responses unfold over time in different empathy networks when viewing same-race and other-race individuals in dynamic painful conditions. We recorded magnetoencephalography signals from Chinese adults when viewing video clips showing a dynamic painful (or non-painful) stimulation to Asian and White models' faces to trigger painful (or neutral) expressions. We found that perceived dynamic pain in Asian models modulated neural activities in the visual cortex at 100 ms-200 ms, in the orbitofrontal and subgenual anterior cingulate cortices at 150 ms-200 ms, in the anterior cingulate cortex around 250 ms-350 ms, and in the temporoparietal junction and middle temporal gyrus around 600 ms after video onset. Perceived dynamic pain in White models modulated activities in the visual, anterior cingulate, and primary sensory cortices after 500 ms. Our findings unraveled earlier dynamic activities in multiple neural circuits in response to same-race (vs other-race) individuals in dynamic painful situations.
Adult ; Humans ; Brain Mapping ; Pain ; Empathy ; Racism ; Gyrus Cinguli/physiology* ; Magnetic Resonance Imaging ; Brain/physiology*

This study aimed to investigate the effect of treadmill exercise on neuropathic pain and to determine whether mitophagy of the anterior cingulate cortex (ACC) contributes to exercise-mediated amelioration of neuropathic pain. Chronic constriction injury of the sciatic nerve (CCI) was used to establish a neuropathic pain model in Sprague-Dawley (SD) rats. Von-Frey filaments were used to assess the mechanical paw withdrawal threshold (PWT), and a thermal radiation meter was used to assess the thermal paw withdrawal latency (PWL) in rats. qPCR was used to evaluate the mRNA levels of Pink1, Parkin, Fundc1, and Bnip3. Western blot was used to evaluate the protein levels of PINK1 and PARKIN. To determine the impact of the mitophagy inducer carbonyl cyanide m-chlorophenylhydrazone (CCCP) on pain behaviors in CCI rats, 24 SD rats were randomly divided into CCI drug control group (CCI+Veh group), CCI+CCCP low-dose group (CCI+CCCP0.25), CCI+CCCP medium-dose group (CCI+CCCP2.5), and CCI+CCCP high-dose group (CCI+CCCP5). Pain behaviors were assessed on 0, 1, 3, 5, and 7 days after modeling. To explore whether exercise regulates pain through mitophagy, 24 SD rats were divided into sham, CCI, and CCI+Exercise (CCI+Exe) groups. The rats in the CCI+Exe group underwent 4-week low-moderate treadmill training one week after modeling. The mechanical pain and thermal pain behaviors of the rats in each group were assessed on 0, 7, 14, 21, and 35 days after modeling. Western blot was used to detect the levels of the mitophagy-related proteins PINK1, PARKIN, LC3 II/LC3 I, and P62 in ACC tissues. Transmission electron microscopy was used to observe the ultrastructure of mitochondrial morphology in the ACC. The results showed that: (1) Compared with the sham group, the pain thresholds of the ipsilateral side of the CCI group decreased significantly (P < 0.001). Meanwhile, the mRNA and protein levels of Pink1 were significantly higher, and those of Parkin were lower in the CCI group (P < 0.05). (2) Compared with the CCI+Veh group, each CCCP-dose group showed higher mechanical and thermal pain thresholds, and the levels of PINK1 and LC3 II/LC3 I were elevated significantly (P < 0.05, P < 0.01). (3) The pain thresholds of the CCI+Exe group increased significantly compared with those of the CCI group after treadmill intervention (P < 0.001, P < 0.01). Compared with the CCI group, the protein levels of PINK1 and P62 were decreased (P < 0.001, P < 0.01), and the protein levels of PARKIN and LC3 II/LC3 I were increased in the CCI+Exe group (P < 0.01, P < 0.05). Rod-shaped mitochondria were observed in the ACC of CCI+Exe group, and there were little mitochondrial fragmentation, swelling, or vacuoles. The results suggest that the mitochondrial PINK1/PARKIN autophagy pathway is blocked in the ACC of neuropathic pain model rats. Treadmill exercise could restore mitochondrial homeostasis and relieve neuropathic pain via the PINK1/PARKIN pathway.
Rats ; Animals ; Mitophagy/physiology* ; Rats, Sprague-Dawley ; Carbonyl Cyanide m-Chlorophenyl Hydrazone/pharmacology* ; Gyrus Cinguli ; Neuralgia ; Ubiquitin-Protein Ligases/metabolism* ; Protein Kinases ; Membrane Proteins/metabolism* ; Mitochondrial Proteins/metabolism*

Itch is an unpleasant sensation that provokes the desire to scratch. While acute itch serves as a protective system to warn the body of external irritating agents, chronic itch is a debilitating but poorly-treated clinical disease leading to repetitive scratching and skin lesions. However, the neural mechanisms underlying the pathophysiology of chronic itch remain mysterious. Here, we identified a cell type-dependent role of the anterior cingulate cortex (ACC) in controlling chronic itch-related excessive scratching behaviors in mice. Moreover, we delineated a neural circuit originating from excitatory neurons of the ACC to the ventral tegmental area (VTA) that was critically involved in chronic itch. Furthermore, we demonstrate that the ACC→VTA circuit also selectively modulated histaminergic acute itch. Finally, the ACC neurons were shown to predominantly innervate the non-dopaminergic neurons of the VTA. Taken together, our findings uncover a cortex-midbrain circuit for chronic itch-evoked scratching behaviors and shed novel insights on therapeutic intervention.
Mice ; Animals ; Gyrus Cinguli/physiology* ; Pruritus/pathology* ; Mesencephalon ; Cerebral Cortex/pathology* ; Neurons/pathology*

Increasing studies have provided cognitive and neuron evidence for not only the similarities, but also the differences between physical pain and social pain in the brain basis. Comparing the similarities and differences of the brain basis of physical pain and social pain helps us to clarify the mechanism of the occurrence and change of pain, and provide theoretical evidence for clinical pain treatment. In this review, we summarized studies to delineate the brain mechanisms of physical pain and social pain. Through the review of existing studies, we found that both physical pain and social pain can invoke the same brain regions that process emotional experience (the dorsal anterior cingulate cortex, anterior insula), emotion regulation (lateral prefrontal cortex) and somatosensory (the posterior insula, secondary sensory cortex). However, the voxel-level activated patterns of physical and social pain differ in the same brain region (dorsal anterior cingulate gyrus, dorsolateral prefrontal cortex, etc.), and the overlapping brain regions (for example, ventrolateral prefrontal cortex) have varied effect on these two types of pain. In addition, studies have shown that the brain activation pattern for social pain may be influenced by the experimental paradigm. Future studies should actively adopt a data-driven way to examine the brain basis of physical pain and social pain, especially the nerve activation mode, aiming to consummate the theory of pain.
Brain ; Gyrus Cinguli ; Humans ; Magnetic Resonance Imaging ; Pain/psychology* ; Prefrontal Cortex/physiology*

Micturition is a complex process involving the bladder, spinal cord, and the brain. Highly sophisticated central neural program controls bladder function by utilizing multiple brain regions, including pons and suprapontine structures. Periaqueductal grey, insula, anterior cingulate cortex, and medial prefrontal cortex are components of suprapontine micturition centers. Under pathologic conditions such as epilepsy, urinary dysfunction is a frequent symptom and it seems to be associated with increased suprapontine cortical activity. Interestingly, micturition can also trigger seizures known as reflex epilepsy. During voiding behavior, frontotemporal cortical activation has been reported and it may induce reflex seizures. As current researches are only limited to present clinical cases, more rigorous investigations are needed to elucidate biological mechanisms of micturition to advance our knowledge on the process of micturition in physiology and pathology.
Brain ; Epilepsy* ; Epilepsy, Reflex ; Gyrus Cinguli ; Pathology ; Physiology ; Pons ; Prefrontal Cortex ; Reflex ; Seizures ; Spinal Cord ; Urinary Bladder ; Urination*

PURPOSE: Reduced brain glucose metabolism and basal forebrain cholinergic neuron degeneration are common features of Alzheimer's disease and have been correlated with memory function. Although regions representing glucose hypometabolism in patients with Alzheimer's disease are targets of cholinergic basal forebrain neurons, the interaction between cholinergic denervation and glucose hypometabolism is still unclear. The aim of the present study was to evaluate glucose metabolism changes caused by cholinergic deficits. MATERIALS AND METHODS: We lesioned basal forebrain cholinergic neurons in rats using 192 immunoglobulin G-saporin. After 3 weeks, lesioned animals underwent water maze testing or were analyzed by 18F-2-fluoro-2-deoxyglucose positron emission tomography. RESULTS: During water maze probe testing, performance of the lesioned group decreased with respect to time spent in the target quadrant and platform zone. Cingulate cortex glucose metabolism in the lesioned group decreased, compared with the normal group. Additionally, acetylcholinesterase activity and glutamate decarboxylase 65/67 expression declined in the cingulate cortex. CONCLUSION: Our results reveal that spatial memory impairment in animals with selective basal forebrain cholinergic neuron damage is associated with a functional decline in the GABAergic and cholinergic system associated with cingulate cortex glucose hypometabolism.
Acetylcholine/metabolism ; Alzheimer Disease ; Animals ; Antibodies, Monoclonal/*pharmacology ; Basal Forebrain/*drug effects/metabolism ; Cholinergic Agents/administration & dosage/*pharmacology ; Cholinergic Neurons/*drug effects/metabolism ; Fluorodeoxyglucose F18 ; GABAergic Neurons/*drug effects/metabolism ; Glucose/*metabolism ; Gyrus Cinguli/*drug effects/metabolism ; Humans ; Injections ; Maze Learning ; Motor Activity/physiology ; Positron-Emission Tomography ; Rats ; Ribosome Inactivating Proteins, Type 1/*pharmacology

This study sought to reveal the difference of brain functions at resting-state between subjects with sub-health and normal controls by using the functional magnetic resonance imaging (fMRI) technology. Resting-state fMRI scans were performed on 24 subjects of sub-health and on 24 healthy controls with gender, age and education matched with the sub-health persons. Compared to the healthy controls, the sub-health group showed significantly higher regional homogeneity (ReHo) in the left post-central gyrus and the right post-central gyrus. On the other hand, the sub-health group showed significantly lower ReHo in the left superior frontal gyrus, in the right anterior cingulated cortex and ventra anterior cingulate gyrus, in the left dorsolateral frontal gyrus, and in the right middle temporal gyrus. The Significant difference in ReHo suggests that the sub-health persons have abnormalities in certain brain regions. It is proved that its specific action and meaning deserves further assessment.
Brain ; physiology ; physiopathology ; Brain Mapping ; Case-Control Studies ; Cerebral Cortex ; Frontal Lobe ; Gyrus Cinguli ; Humans ; Magnetic Resonance Imaging ; Parietal Lobe

OBJECTIVETo compare the effects of electroacupuncture (EA) and moxibustion therapies on patients with diarrhea-predominant irritable bowel syndrome (D-IBS).

METHODSA total of 60 D-IBS patients were randomly allocated to the EA group (30 cases) and moxibustion group (30 cases). Before and after treatment, the gastrointestinal symptoms and psychological symptoms were scored by Visual Analogue Scale, Bristol Stool Form Scale, Hamilton Anxiety Rating Scale (HAMA), and Hamilton Depression Rating Scale (HAMD); the expressions of 5-hydroxytryptamine (5-HT), 5-HT3 receptor (5-HT3R), and 5-HT4 receptor (5-HT4R) in the sigmoid mucosal tissue were measured by immunohistochemical staining. Additionally, the effects on the functional brain areas of the anterior cingulate cortex (ACC), insular cortex (IC) and prefrontal cortex (PFC) were observed by functional magnetic resonance imaging.

RESULTSCompared with before treatment, both EA and moxibustion groups reported significant improvements in abdominal pain and abdominal bloating after treatment (P<0.01 or P<0.05). The moxibustion group reported greater improvements in defecation emergency, defecation frequency, and stool feature than the EA group (P<0.01). Both HAMA and HAMD scores were significantly decreased in the moxibustion group than in the EA group (P<0.01). Both groups demonstrated significantly reduced expressions of 5-HT, 5-HT3R and 5-HT4R in the colonic mucosa after treatment (P<0.01), with a greater reduction of 5-HT in the moxibustion group (P<0.05). Finally, decreased activated voxel values were observed in the left IC, right IC and PFC brain regions of patients in the moxibustion group under stimulation with 150 mL colorectal distension after treatment (P<0.05 or P<0.01), while in the EA group only PFC area demonstrated a reduction (P<0.05).

CONCLUSIONMoxibustion can significantly improve the symptoms of D-IBS, suggesting that moxibustion may be a more effective therapy than EA for D-IBS patients.

Adult ; Anxiety ; Brain ; physiology ; Cerebral Cortex ; physiopathology ; Colon, Sigmoid ; chemistry ; Depression ; Diarrhea ; physiopathology ; Electroacupuncture ; Gastrointestinal Tract ; physiology ; Gyrus Cinguli ; physiopathology ; Humans ; Immunohistochemistry ; Intestinal Mucosa ; chemistry ; Irritable Bowel Syndrome ; physiopathology ; psychology ; therapy ; Magnetic Resonance Imaging ; Moxibustion ; Pain Measurement ; Prefrontal Cortex ; physiopathology ; Receptors, Serotonin, 5-HT3 ; analysis ; Serotonin ; analysis