scholarly journals Nociceptive Processing by Anterior Cingulate Pyramidal Neurons

2010 ◽  
Vol 103 (6) ◽  
pp. 3287-3301 ◽  
Author(s):  
Bai-Chuang Shyu ◽  
Robert W. Sikes ◽  
Leslie J. Vogt ◽  
Brent A. Vogt
Keyword(s):  
Pyramidal Neurons ◽  
Cingulate Cortex ◽  
Anterior Cingulate ◽  
Projection Neurons ◽  
Noxious Stimulation ◽  
Axon Collateral ◽  
Postsynaptic Potentials ◽  
Nociceptive Responses ◽  
Nociceptive Afferents ◽  
Layer V

Although the cingulate cortex is frequently activated in acute human pain studies, postsynaptic responses are not known nor are links between nociceptive afferents, neuronal responses, and outputs to other structures. Intracellular potentials were recorded from neurobiotin-injected, pyramidal neurons in anterior cingulate area 24b following noxious stimulation of the sciatic nerve in anesthetized rabbits. Layer IIIc pyramids had extensive and horizontally oriented basal dendrites in layer IIIc where nociceptive afferents terminate. They had the longest excitatory postsynaptic potentials (EPSPs; 545 ms) that were modulated with hyperpolarizing currents. Pyramids in layer V had an intermediate tuft of oblique apical dendrites in layer IIIc that were 150–350 μm from somata in layer Va and 351–550 μm in layer Vb. Although average EPSP durations were short in layers II–IIIab (222 ± 31), Va (267 ± 65), and Vb (159 ± 31), there were five neurons in layers IIIab–Va that had EPSP durations lasting >300 ms (548 ± 63 ms). Neurons in layers IIIc, Va, and Vb had the highest amplitude EPSPs (6.25, 6.84 ± 0.58, and 6.4 ± 0.47 mV, respectively), whereas those in layers II–IIIab were 5 ± 0.56 mV. Nociceptive responses in layer Vb were complex and some had initial inhibitory postsynaptic potentials with shorter-duration EPSPs. Layers II–IIIab had dye-coupled pyramids and EPSPs in these layers had short durations (167 ± 33 ms) compared with those in layers IIIc–Va (487 ± 28 ms). In conclusion there are two populations of anterior cingulate cortex pyramids with EPSPs of significantly different durations, although their dendritic morphologies do not predict EPSP duration. Short-duration EPSPs are thalamic-mediated, nociceptive responses lasting ≤200 ms. Longer, “integrative” EPSPs are >350 ms and are likely modulated by intracortical axon collateral discharges. These findings suggest that links between nociception and projections to cortical and motor systems are instantaneous because nociceptive responses are generated directly by pyramidal projection neurons in all layers.

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 Stress-induced modulation of nociceptive responses in the rat anterior cingulate cortex

2013 ◽  
Vol 12 (02) ◽  
pp. 235-246 ◽  
Author(s):  
Hiromi Yamashita ◽  
Jorge L. Zeredo ◽  
Kei Kaida ◽  
Mari Kimoto ◽  
Izumi Asahina ◽  
...  
Keyword(s):  
Anterior Cingulate Cortex ◽  
Cingulate Cortex ◽  
Anterior Cingulate ◽  
Nociceptive Responses

Intracortical Circuits in Rat Anterior Cingulate Cortex Are Activated by Nociceptive Inputs Mediated by Medial Thalamus

2006 ◽  
Vol 96 (6) ◽  
pp. 3409-3422 ◽  
Author(s):  
Jenq-Wei Yang ◽  
Hsi-Chien Shih ◽  
Bai-Chuang Shyu
Keyword(s):  
Anterior Cingulate Cortex ◽  
Current Source ◽  
Cingulate Cortex ◽  
Anterior Cingulate ◽  
High Frequency Stimulation ◽  
Evoked Responses ◽  
Synaptic Organization ◽  
Sprague Dawley ◽  
Intracortical Circuits ◽  
Layer V

We investigated the afferents and intracortical synaptic organization of the anterior cingulate cortex (ACC) during noxious electrical stimulation. Extracellular field potentials were recorded simultaneously from 16 electrodes spanning all layers of the ACC in male Sprague–Dawley rats anesthetized by halothane inhalation. Laminar-specific transmembrane currents were calculated with the current source density analysis method. Two major groups of evoked sink currents were identified: an early group (latency = 54.04 ± 2.12 ms; 0.63 ± 0.07 mV/mm2) in layers V–VI and a more intense late group (latency = 80.07 ± 4.85 ms; 2.16 ± 0.22 mV/mm2) in layer II/III and layer V. Multiunit activities were evoked mainly in layer V and deep layer II/III with latencies similar to that of the early and late sink groups. The evoked EPSP latencies of pyramidal neurons in layers II/III and V related closely with the sink currents. The sink currents were inhibited by intracortical injection of CNQX (1 mM, 1 μl), a glutaminergic receptor antagonist, and enhanced by intraperitoneal (5 mg/kg) and intracortical (10 μg/μl, 1 μl) injection of morphine, a μ-opioid receptor agonist. Paired-pulse depression was observed with interpulse intervals of 50 to 1,000 ms. High-frequency stimulation (100 Hz, 11 pulses) enhanced evoked responses in the ACC and evoked medial thalamic (MT) unit activities. MT lesions blocked evoked responses in the ACC. Our results demonstrated that two distinct synaptic circuits in the ACC were activated by noxious stimuli and that the MT is the major thalamic relay that transmits nociceptive information to the ACC.

scholarly journals Metabolite activity in the anterior cingulate cortex during a painful stimulus using functional MRS

2020 ◽  
Vol 10 (1) ◽  
Author(s):  
J. Archibald ◽  
E. L. MacMillan ◽  
C. Graf ◽  
P. Kozlowski ◽  
C. Laule ◽  
...  
Keyword(s):  
Anterior Cingulate Cortex ◽  
Cingulate Cortex ◽  
Anterior Cingulate ◽  
Noxious Stimulation ◽  
Resonance Spectroscopy ◽  
Large Effect Size ◽  
Brain Responses ◽  
Pain Outcomes ◽  
Healthy Participants

Abstract To understand neurochemical brain responses to pain, proton magnetic resonance spectroscopy (1H-MRS) is used in humans in vivo to examine various metabolites. Recent MRS investigations have adopted a functional approach, where acquisitions of MRS are performed over time to track task-related changes. Previous studies suggest glutamate is of primary interest, as it may play a role during cortical processing of noxious stimuli. The objective of this study was to examine the metabolic effect (i.e., glutamate) in the anterior cingulate cortex during noxious stimulation using fMRS. The analysis addressed changes in glutamate and glutamate + glutamine (Glx) associated with the onset of pain, and the degree by which fluctuations in metabolites corresponded with continuous pain outcomes. Results suggest healthy participants undergoing tonic noxious stimulation demonstrated increased concentrations of glutamate and Glx at the onset of pain. Subsequent reports of pain were not accompanied by corresponding changes in glutamate of Glx concentrations. An exploratory analysis on sex revealed large effect size changes in glutamate at pain onset in female participants, compared with medium-sized effects in male participants. We propose a role for glutamate in the ACC related to the detection of a noxious stimulus.

scholarly journals Glutamatergic Nonpyramidal Neurons From Neocortical Layer VI and Their Comparison With Pyramidal and Spiny Stellate Neurons

2009 ◽  
Vol 101 (2) ◽  
pp. 641-654 ◽  
Author(s):  
Sofija Andjelic ◽  
Thierry Gallopin ◽  
Bruno Cauli ◽  
Elisa L. Hill ◽  
Lisa Roux ◽  
...  
Keyword(s):  
Pyramidal Neurons ◽  
Glutamate Transporter ◽  
Gabaergic Interneuron ◽  
Acid Decarboxylase ◽  
Projection Neurons ◽  
Heterogeneous Cluster ◽  
Glutamatergic Neurons ◽  
Layer V ◽  
Nonpyramidal Neurons ◽  
Layer Vi

The deeper part of neocortical layer VI is dominated by nonpyramidal neurons, which lack a prominent vertically ascending dendrite and predominantly establish corticocortical connections. These neurons were studied in rat neocortical slices using patch-clamp, single-cell reverse transcription–polymerase chain reaction, and biocytin labeling. The majority of these neurons expressed the vesicular glutamate transporter but not glutamic acid decarboxylase, suggesting that a high proportion of layer VI nonpyramidal neurons are glutamatergic. Indeed, they exhibited numerous dendritic spines and established asymmetrical synapses. Our sample of glutamatergic nonpyramidal neurons displayed a wide variety of somatodendritic morphologies and a subset of these cells expressed the Nurr1 mRNA, a marker for ipsilateral, but not commissural corticocortical projection neurons in layer VI. Comparison with spiny stellate and pyramidal neurons from other layers showed that glutamatergic neurons consistently exhibited a low occurrence of GABAergic interneuron markers and regular spiking firing patterns. Analysis of electrophysiological diversity using unsupervised clustering disclosed three groups of cells. Layer V pyramidal neurons were segregated into a first group, whereas a second group consisted of a subpopulation of layer VI neurons exhibiting tonic firing. A third heterogeneous cluster comprised spiny stellate, layer II/III pyramidal, and layer VI neurons exhibiting adaptive firing. The segregation of layer VI neurons in two different clusters did not correlate either with their somatodendritic morphologies or with Nurr1 expression. Our results suggest that electrophysiological similarities between neocortical glutamatergic neurons extend beyond layer positioning, somatodendritic morphology, and projection specificity.

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.

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