scholarly journals NCAM Regulates Inhibition and Excitability in Layer 2/3 Pyramidal Cells of Anterior Cingulate Cortex

2017 ◽  
Vol 11 ◽  
Author(s):  
Xuying Zhang ◽  
Chelsea S. Sullivan ◽  
Megan B. Kratz ◽  
Michael R. Kasten ◽  
Patricia F. Maness ◽  
...  
Keyword(s):  
Anterior Cingulate Cortex ◽  
Pyramidal Cells ◽  
Cingulate Cortex ◽  
Anterior Cingulate ◽  
Layer 2

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 NMDA GluN2C/2D receptors contribute to synaptic regulation and plasticity in the anterior cingulate cortex of adult mice

2021 ◽  
Vol 14 (1) ◽  
Author(s):  
Qi-Yu Chen ◽  
Xu-Hui Li ◽  
Jing-Shan Lu ◽  
Yinglu Liu ◽  
Jung-Hyun Alex Lee ◽  
...  
Keyword(s):  
Anterior Cingulate Cortex ◽  
Glutamate Release ◽  
Critical Role ◽  
Pyramidal Cells ◽  
Cingulate Cortex ◽  
Long Term Potentiation ◽  
Anterior Cingulate ◽  
Cortical Region ◽  
Adult Mice

Abstract Introduction N-Methyl-D-aspartate receptors (NMDARs) play a critical role in different forms of plasticity in the central nervous system. NMDARs are always assembled in tetrameric form, in which two GluN1 subunits and two GluN2 and/or GluN3 subunits combine together. Previous studies focused mainly on the hippocampus. The anterior cingulate cortex (ACC) is a key cortical region for sensory and emotional functions. NMDAR GluN2A and GluN2B subunits have been previously investigated, however much less is known about the GluN2C/2D subunits. Results In the present study, we found that the GluN2C/2D subunits are expressed in the pyramidal cells of ACC of adult mice. Application of a selective antagonist of GluN2C/2D, (2R*,3S*)-1-(9-bromophenanthrene-3-carbonyl) piperazine-2,3-dicarboxylic acid (UBP145), significantly reduced NMDAR-mediated currents, while synaptically evoked EPSCs were not affected. UBP145 affected neither the postsynaptic long-term potentiation (post-LTP) nor the presynaptic LTP (pre-LTP). Furthermore, the long-term depression (LTD) was also not affected by UBP145. Finally, both UBP145 decreased the frequency of the miniature EPSCs (mEPSCs) while the amplitude remained intact, suggesting that the GluN2C/2D may be involved in presynaptic regulation of spontaneous glutamate release. Conclusions Our results provide direct evidence that the GluN2C/2D contributes to evoked NMDAR mediated currents and mEPSCs in the ACC, which may have significant physiological implications.

scholarly journals Ascending noradrenergic excitation from the locus coeruleus to the anterior cingulate cortex

2020 ◽  
Vol 13 (1) ◽  
Author(s):  
Kohei Koga ◽  
Akihiro Yamada ◽  
Qian Song ◽  
Xu-Hui Li ◽  
Qi-Yu Chen ◽  
...  
Keyword(s):  
Locus Coeruleus ◽  
Anterior Cingulate Cortex ◽  
Behavioral Sensitization ◽  
Pyramidal Cells ◽  
Cingulate Cortex ◽  
Anterior Cingulate ◽  
Subcortical Structures ◽  
Electron Microscopic ◽  
Excitatory Transmission

AbstractAnterior cingulate cortex (ACC) plays important roles in sensory perception including pain and itch. Neurons in the ACC receive various neuromodulatory inputs from subcortical structures, including locus coeruleus noradrenaline (LC-NA) neurons. Few studies have been reported about synaptic and behavioral functions of LC-NA projections to the ACC. Using viral-genetic method (AAV-DIO-eYFP) on DBH-cre mice, we found that LC-NA formed synaptic connections to ACC pyramidal cells but not interneurons. This is further supported by the electron microscopic study showing NAergic fibers contact the presynaptic inputs and post-synaptic areas of the pyramidal cells. NA application produced both pre- and post-synaptic potentiation effects in ACC excitatory transmission in vivo and in vitro. Activation of LC-NA projection to the ACC by optogenetic method produced enhancement of excitatory transmission in vitro and induced scratching and behavioral sensitization for mechanical stimulation. Our results demonstrate that LC-NA projections enhance or facilitate brain responses to pain and itch by potentiating glutamatergic synaptic transmissions in the ACC.

scholarly journals GABAergic cell transplants in the anterior cingulate cortex reduce neuropathic pain aversiveness

Brain ◽  
2019 ◽  
Vol 142 (9) ◽  
pp. 2655-2669 ◽  
Author(s):  
Dina L Juarez-Salinas ◽  
Joao M Braz ◽  
Alexander Etlin ◽  
Steven Gee ◽  
Vikaas Sohal ◽  
...  
Keyword(s):  
Neuropathic Pain ◽  
Anterior Cingulate Cortex ◽  
Pyramidal Cells ◽  
Cingulate Cortex ◽  
Inhibitory Interneuron ◽  
Anterior Cingulate ◽  
Gaba A ◽  
Ongoing Pain ◽  
Rostral Anterior Cingulate Cortex ◽  
Posterior Anterior

Abstract Dysfunction of inhibitory circuits in the rostral anterior cingulate cortex underlies the affective (aversive), but not the sensory-discriminative features (hypersensitivity) of the pain experience. To restore inhibitory controls, we transplanted inhibitory interneuron progenitor cells into the rostral anterior cingulate cortex in a chemotherapy-induced neuropathic pain model. The transplants integrated, exerted a GABA-A mediated inhibition of host pyramidal cells and blocked gabapentin preference (i.e. relieved ongoing pain) in a conditioned place preference paradigm. Surprisingly, pain aversiveness persisted when the transplants populated both the rostral and posterior anterior cingulate cortex. We conclude that selective and long lasting inhibition of the rostral anterior cingulate cortex, in the mouse, has a profound pain relieving effect against nerve injury-induced neuropathic pain. However, the interplay between the rostral and posterior anterior cingulate cortices must be considered when examining circuits that influence ongoing pain and pain aversiveness.

The Increased In Vivo Firing of Pyramidal Cells But not Interneurons in the Anterior Cingulate Cortex After Neuropathic Pain

2021 ◽  
Author(s):  
Da-Yu Zhu ◽  
Ting-Ting Cao ◽  
Hong-Wei Fan ◽  
Ming-Zhe Zhang ◽  
Hao-Kai Duan ◽  
...  
Keyword(s):  
Chronic Pain ◽  
Neuropathic Pain ◽  
Firing Rate ◽  
Anterior Cingulate Cortex ◽  
Pyramidal Cells ◽  
Cingulate Cortex ◽  
Anterior Cingulate ◽  
High Frequency Stimulation ◽  
Nociceptive Information

Abstract Chronic pain damages the balance between excitation and inhibition in the sensory cortex. It has been confirmed that the activity of cortical glutamatergic pyramidal cells increases after chronic pain. However, whether the activity of inhibitory interneurons synchronized changed remains obscure, especially in in vivo conditions. In the present study, we checked the firing rate of pyramidal cells and interneurons in the anterior cingulate cortex, a main cortical area for the regulation of nociceptive information in mice with spared nerve injury by using in vivo multi-channel recording system. We found that the firing rate of pyramidal cells but not interneurons increased in the ACC, which is further confirmed by the increased FOS expression in pyramidal cells but not interneurons, in mice with neuropathic pain. Selectively high frequency stimulation of the ACC nociceptive afferent fibers only potentiated the activity of pyramidal cells either. Our results thus suggest that the increased activity of pyramidal cells contributes to the damaged E/I balance in the ACC and is important for the pain hypersensitivity in mice with neuropathic pain.

scholarly journals Ascending noradrenergic excitation from the locus coeruleus to the anterior cingulate cortex

2020 ◽  
Author(s):  
Kohei Koga ◽  
Akihiro Yamada ◽  
Qian Song ◽  
Xu-Hui Li ◽  
Qi-Yu Chen ◽  
...  
Keyword(s):  
Locus Coeruleus ◽  
Anterior Cingulate Cortex ◽  
Behavioral Sensitization ◽  
Pyramidal Cells ◽  
Cingulate Cortex ◽  
Anterior Cingulate ◽  
Subcortical Structures ◽  
Electron Microscopic ◽  
Excitatory Transmission

Abstract Anterior cingulate cortex (ACC) plays important roles in sensory perception including pain and itch. Neurons in the ACC receive various neuromodulatory inputs from subcortical structures, including locus coeruleus noradrenaline (LC-NA) neurons. Few studies have been reported about synaptic and behavioral functions of LC-NA projections to the ACC. Using viral-genetic method (AAV-DIO-eYFP) on DBH-cre mice, we found that LC-NA formed synaptic connections to ACC pyramidal cells but not interneurons. This is further supported by the electron microscopic study showing NAergic fibers contact the presynaptic inputs and post-synaptic areas of the pyramidal cells. NA application produced both pre- and post-synaptic potentiation effects in ACC excitatory transmission in vivo and in vitro. Activation of LC-NA projection to the ACC by optogenetic method produced enhancement of excitatory transmission in vitro and induced scratching and behavioral sensitization for mechanical stimulation. Our results demonstrate that LC-NA projections enhance or facilitate brain responses to pain and itch by potentiating glutamatergic synaptic transmissions in the ACC.

scholarly journals Ascending noradrenergic excitation from the locus coeruleus to the anterior cingulate cortex

2020 ◽  
Author(s):  
Kohei Koga ◽  
Akihiro Yamada ◽  
Qian Song ◽  
Xu-Hui Li ◽  
Qi-Yu Chen ◽  
...  
Keyword(s):  
Locus Coeruleus ◽  
Anterior Cingulate Cortex ◽  
Behavioral Sensitization ◽  
Pyramidal Cells ◽  
Cingulate Cortex ◽  
Anterior Cingulate ◽  
Subcortical Structures ◽  
Electron Microscopic ◽  
Excitatory Transmission

Abstract Anterior cingulate cortex (ACC) plays important roles in sensory perception including pain and itch. Neurons in the ACC receive various neuromodulatory inputs from subcortical structures, including locus coeruleus noradrenaline (LC-NA) neurons. Few studies have been reported about synaptic and behavioral functions of LC-NA projections to the ACC. Using viral-genetic method (AAV-DIO-eYFP) on DBH-cre mice, we found that LC-NA formed synaptic connections to ACC pyramidal cells but not interneurons. This is further supported by the electron microscopic study showing NAergic fibers contact the presynaptic inputs and post-synaptic areas of the pyramidal cells. NA application produced both pre- and post-synaptic potentiation effects in ACC excitatory transmission in vivo and in vitro . Activation of LC-NA projection to the ACC by optogenetic method produced enhancement of excitatory transmission in vitro and induced scratching and behavioral sensitization for mechanical stimulation. Our results demonstrate that LC-NA projections enhance or facilitate brain responses to pain and itch by potentiating glutamatergic synaptic transmissions in the ACC.

scholarly journals Anterior Cingulate Cortex Mediates Hyperalgesia and Anxiety Induced by Chronic Pancreatitis in Rats

2021 ◽  
Author(s):  
Dan Ren ◽  
Jia-Ni Li ◽  
Xin-Tong Qiu ◽  
Fa-Ping Wan ◽  
Zhen-Yu Wu ◽  
...  
Keyword(s):  
Chronic Pancreatitis ◽  
Anterior Cingulate Cortex ◽  
Membrane Trafficking ◽  
Glutamate Transporter ◽  
Pyramidal Cells ◽  
Cingulate Cortex ◽  
Anterior Cingulate ◽  
Morphological Data ◽  
Trinitrobenzene Sulfonic Acid ◽  
Cortical Modulation

AbstractCentral sensitization is essential in maintaining chronic pain induced by chronic pancreatitis (CP), but cortical modulation of painful CP remains elusive. Here, we examined the role of the anterior cingulate cortex (ACC) in the pathogenesis of abdominal hyperalgesia in a rat model of CP induced by intraductal administration of trinitrobenzene sulfonic acid (TNBS). TNBS treatment resulted in long-term abdominal hyperalgesia and anxiety in rats. Morphological data indicated that painful CP induced a significant increase in FOS-expressing neurons in the nucleus tractus solitarii (NTS) and ACC, and some FOS-expressing neurons in the NTS projected to the ACC. In addition, a larger portion of ascending fibers from the NTS innervated pyramidal neurons, the neural subpopulation primarily expressing FOS under the condition of painful CP, rather than GABAergic neurons within the ACC. CP rats showed increased expression of vesicular glutamate transporter 1, and increased membrane trafficking and phosphorylation of the N-methyl-D-aspartate receptor (NMDAR) subunit NR2B and the α-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid receptor (AMPAR) subunit GluR1 within the ACC. Microinjection of NMDAR and AMPAR antagonists into the ACC to block excitatory synaptic transmission significantly attenuated abdominal hyperalgesia in CP rats, which was similar to the analgesic effect of endomorphins injected into the ACC. Specifically inhibiting the excitability of ACC pyramidal cells via chemogenetics reduced both hyperalgesia and comorbid anxiety, whereas activating these neurons via optogenetics failed to aggravate hyperalgesia and anxiety in CP rats. Taken together, these findings provide neurocircuit, biochemical, and behavioral evidence for involvement of the ACC in hyperalgesia and anxiety in CP rats, as well as novel insights into the cortical modulation of painful CP, and highlights the ACC as a potential target for neuromodulatory interventions in the treatment of painful CP.

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