scholarly journals Juvenile Emotional Experience Alters Synaptic Inputs on Pyramidal Neurons in the Anterior Cingulate Cortex

2001 ◽  
Vol 11 (8) ◽  
pp. 717-727 ◽  
Author(s):  
C. Helmeke
Keyword(s):  
Anterior Cingulate Cortex ◽  
Pyramidal Neurons ◽  
Emotional Experience ◽  
Cingulate Cortex ◽  
Anterior Cingulate ◽  
Synaptic Inputs

scholarly journals Control of impulsivity by Gi-protein signalling in layer-5 pyramidal neurons of the anterior cingulate cortex

2021 ◽  
Vol 4 (1) ◽  
Author(s):  
Bastiaan van der Veen ◽  
Sampath K. T. Kapanaiah ◽  
Kasyoka Kilonzo ◽  
Peter Steele-Perkins ◽  
Martin M. Jendryka ◽  
...  
Keyword(s):  
Gene Expression ◽  
Anterior Cingulate Cortex ◽  
Expression Analysis ◽  
Gene Expression Analysis ◽  
Pyramidal Neurons ◽  
Treatment Options ◽  
Pyramidal Cells ◽  
Cingulate Cortex ◽  
Cell Types ◽  
Anterior Cingulate

AbstractPathological impulsivity is a debilitating symptom of multiple psychiatric diseases with few effective treatment options. To identify druggable receptors with anti-impulsive action we developed a systematic target discovery approach combining behavioural chemogenetics and gene expression analysis. Spatially restricted inhibition of three subdivisions of the prefrontal cortex of mice revealed that the anterior cingulate cortex (ACC) regulates premature responding, a form of motor impulsivity. Probing three G-protein cascades with designer receptors, we found that the activation of Gi-signalling in layer-5 pyramidal cells (L5-PCs) of the ACC strongly, reproducibly, and selectively decreased challenge-induced impulsivity. Differential gene expression analysis across murine ACC cell-types and 402 GPCRs revealed that - among Gi-coupled receptor-encoding genes - Grm2 is the most selectively expressed in L5-PCs while alternative targets were scarce. Validating our approach, we confirmed that mGluR2 activation reduced premature responding. These results suggest Gi-coupled receptors in ACC L5-PCs as therapeutic targets for impulse control disorders.

scholarly journals Neuroinflammation in the anterior cingulate cortex: the potential supraspinal mechanism underlying the mirror-image pain following motor fiber injury

2022 ◽  
Author(s):  
Qiao-Yun Li ◽  
Pei-Wen Yao ◽  
Jin-Yu Liu ◽  
Yi-Wen Duan ◽  
Shao-Xia Chen ◽  
...  
Keyword(s):  
Anterior Cingulate Cortex ◽  
Nerve Injury ◽  
Mechanical Allodynia ◽  
Pyramidal Neurons ◽  
Cingulate Cortex ◽  
Mirror Image ◽  
Anterior Cingulate ◽  
Designer Drugs ◽  
Cortical Region ◽  
Tnf Α

Abstract Background: Peripheral nerve inflammation or lesion can affect contralateral healthy structures, and thus results in mirror-image pain. Supraspinal structures play important roles in the occurrence of mirror pain. The anterior cingulate cortex (ACC) is a first order cortical region that responds to painful stimuli. In the present study, we systematically investigate and compare the neuroimmune changes in the bilateral ACC region using unilateral- (spared nerve injury, SNI) and mirror-(L5 ventral root transection, L5-VRT) pain models, aiming to explore the potential supraspinal neuroimmune mechanism underlying the mirror-image pain. Methods: The up-and-down method with von Frey hairs was used to measure the mechanical allodynia. Viral injections for the designer receptors exclusively activated by designer drugs (DREADD) were used to modulate ACC pyramidal neurons. Immunohistochemistry, immunofluorescence, western blotting, protein microarray were used to detect the regulation of inflammatory signaling.Results: Increased expressions of tumor necrosis factor alpha (TNF-α), interleukin-6 (IL-6) and chemokine CX3CL1 in ACC induced by unilateral nerve injury were observed on the contralateral side in the SNI group but on the bilateral side in the L5-VRT group, representing a stronger immune response to L5-VRT surgery. In remote ACC, both SNI and L5-VRT induced robust bilateral increase in the protein level of Nav1.6 (SCN8A), a major voltage-gated sodium channel (VGSC) that regulates neuronal activity in the mammalian nervous system. However, the L5-VRT-induced Nav1.6 response occurred at PO 3d, earlier than the SNI-induced one, 7 days after surgery. Modulating ACC pyramidal neurons via DREADD-Gq or DREADD-Gi greatly changed the ACC CX3CL1 levels and the mechanical paw withdrawal threshold. Neutralization of endogenous ACC CX3CL1 by contralateral anti-CX3CL1 antibody attenuated the induction and the maintenance of mechanical allodynia and eliminated the upregulation of CX3CL1, TNF-α and Nav1.6 protein levels in ACC induced by SNI. Furthermore, contralateral ACC anti-CX3CL1 also inhibited the expression of ipsilateral spinal c-Fos, Iba1, CD11b, TNF-α and IL-6. Conclusions: The descending facilitation function mediated by CX3CL1 and its downstream cascade may play a pivotal role, leading to enhanced pain sensitization and even mirror-image pain. Strategies that target chemokine-mediated ACC hyperexcitability may lead to novel therapies for the treatment of neuropathic pain.

Neural Correlates of Levels of Emotional Awareness: Evidence of an Interaction between Emotion and Attention in the Anterior Cingulate Cortex

1998 ◽  
Vol 10 (4) ◽  
pp. 525-535 ◽  
Author(s):  
Richard D. Lane ◽  
Eric M. Reiman ◽  
Beatrice Axelrod ◽  
Lang-Sheng Yun ◽  
Andrew Holmes ◽  
...  
Keyword(s):  
Individual Differences ◽  
Anterior Cingulate Cortex ◽  
Response Selection ◽  
Emotional Experience ◽  
Cingulate Cortex ◽  
Emotional Awareness ◽  
Neural Correlates ◽  
Anterior Cingulate ◽  
Positron Emission ◽  
Conjunction Analysis

Recent functional imaging studies have begun to identify the neural correlates of emotion in healthy volunteers. However, studies to date have not differentially addressed the brain areas associated with the perception, experience, or expression of emotion during emotional arousal. To explore the neural correlates of emotional experience, we used positron emission tomography (PET) and 15O-water to measure cerebral blood flow (CBF) in 12 healthy women during film- and recall-induced emotion and correlated CBF changes attributable to emotion with subjects' scores on the Levels of Emotional Awareness Scale (LEAS), a measure of individual differences in the capacity to experience emotion in a differentiated and complex way. A conjunction analysis revealed that the correla-tions between LEAS and CBF during film- and recall-induced emotion overlapped significantly (z = 3.74, p < 0.001) in Brod-mann's area 24 of the anterior cingulate cortex (ACC). This finding suggests that individual differences in the ability to accurately detect emotional signals interoceptively or exteroceptively may at least in part be a function of the degree to which the ACC participates in the experiential processing and response to emotion cues. To the extent that this finding is consistent with the functions of the ACC involving attention and response selection, it suggests that this neural correlate of conscious emotional experience is not exclusive to emotion.

scholarly journals Decreased dopaminergic inhibition of pyramidal neurons in anterior cingulate cortex maintains chronic neuropathic pain

Cell Reports ◽  
2021 ◽  
Vol 37 (9) ◽  
pp. 109933
Author(s):  
Kevin Lançon ◽  
Chaoling Qu ◽  
Edita Navratilova ◽  
Frank Porreca ◽  
Philippe Séguéla
Keyword(s):  
Neuropathic Pain ◽  
Anterior Cingulate Cortex ◽  
Pyramidal Neurons ◽  
Cingulate Cortex ◽  
Anterior Cingulate ◽  
Chronic Neuropathic Pain

scholarly journals Neuropathic Pain Linked to Defective Dopaminergic Inhibition in Anterior Cingulate Cortex

2020 ◽  
Author(s):  
Kevin Lançon ◽  
Edita Navratilova ◽  
Frank Porreca ◽  
Philippe Séguéla
Keyword(s):  
Neuropathic Pain ◽  
Anterior Cingulate Cortex ◽  
Pyramidal Neurons ◽  
Critical Role ◽  
Input Resistance ◽  
Cingulate Cortex ◽  
Anterior Cingulate ◽  
Hcn Channels ◽  
Prefrontal Region ◽  
Affective Components

AbstractPyramidal neurons in the anterior cingulate cortex (ACC), a prefrontal region involved in processing the affective components of pain, display hyperexcitability in chronic neuropathic conditions and their silencing abolishes hyperalgesia in rodents. We show here that dopamine, through D1-like receptor signaling, inhibits layer 2/3 pyramidal neurons of mouse ACC. Hyperpolarization-activated cyclic nucleotide-gated (HCN) channels control the firing activity of these pyramidal neurons. Through Gs-coupled D1-like receptors, dopamine induces the opening of HCN channels at physiological membrane potentials, driving a significant decrease in input resistance and excitability. Systemic L-DOPA rescues HCN channel activity, pyramidal excitability in ACC as well as sensory phenotype in neuropathic mice while microinjection of a selective D1-like agonist in ACC induces relief of ongoing pain in neuropathic animals. We conclude that decreased dopaminergic inhibition in ACC plays a critical role in an abnormal top-down modulation leading to neuropathic pain.

scholarly journals Differential Vulnerability of Anterior Cingulate Cortex Cell-Types to Diseases and Drugs

2021 ◽  
Author(s):  
Rammohan Shukla ◽  
Marissa Ann Smail ◽  
Sapuni Sureshika Chandrasena ◽  
Xiaolu Zhang ◽  
Vineet Reddy ◽  
...  
Keyword(s):  
Psychiatric Disorders ◽  
Anterior Cingulate Cortex ◽  
Pyramidal Neurons ◽  
Deep Layer ◽  
Cingulate Cortex ◽  
Cell Types ◽  
Disease State ◽  
Anterior Cingulate ◽  
Rnaseq Data ◽  
Functional Profiles

In psychiatric disorders, mismatches between disease-states and therapeutic strategies are highly pronounced, largely because of unanswered questions regarding specific vulnerabilities of different cell-types and therapeutic responses. Which cellular events (housekeeping or salient) are most affected? Which cell-types succumb first to challenges, and which exhibit the strongest response to drugs? Are these events coordinated between cell-types? How does the disease-state and drug affect this coordination? To address these questions, we analyzed single-nucleus-RNAseq (sn-RNAseq) data from the human anterior cingulate cortex- a region involved in many psychiatric disorders. Density index, a metric for quantifying similarities and dissimilarities across functional profiles, was employed to identify common (housekeeping) or salient functional themes across all cell-types. Cell-specific signatures were integrated with existing disease and drug-specific signatures to determine cell-type-specific vulnerabilities, druggabilities, and responsiveness. Clustering of functional profiles revealed cell-types jointly participating in these events. SST and VIP interneurons were found to be most vulnerable, whereas pyramidal neurons were least vulnerable. Overall, the disease-state is superficial layer-centric, largely influences cell-specific salient themes, strongly impacts disinhibitory neurons, and influences astrocyte interaction with a subset of deep-layer pyramidal neurons. Drug activities, on the other hand, are deep layer-centric and involve activating a distinct subset of deep-layer pyramidal neurons to circumvent the disinhibitory circuit malfunctioning in the disease-state. These findings demonstrate a novel application of sn-RNAseq data to explain drug and disease action at a systems level, suggests a targeted drug development and reevaluate various postmortem-based findings.

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