Adenylyl cyclase subtype 1 is essential for late-phase long term potentiation and spatial propagation of synaptic responses in the anterior cingulate cortex of adult mice
Reads0
Chats0
TLDR
There is strong evidence that the selective AC1 inhibitor NB001 can be used to inhibit pain-related cortical L-LTP without affecting basal synaptic transmission and basic mechanisms for possible side effects of gabapentin in the central nervous system and its ineffectiveness in some patients with neuropathic pain are provided.Abstract:
Long-term potentiation (LTP) is a key cellular mechanism for pathological pain in the central nervous system. LTP contains at least two different phases: early-phase LTP (E-LTP) and late-phase LTP (L-LTP). Among several major cortical areas, the anterior cingulate cortex (ACC) is a critical brain region for pain perception and its related emotional changes. Periphery tissue or nerve injuries cause LTP of excitatory synaptic transmission in the ACC. Our previous studies have demonstrated that genetic deletion of calcium-stimulated adenylyl cyclase 1 (AC1) or pharmacological application of a selective AC1 inhibitor NB001 blocked E-LTP in the ACC. However, the effect of AC1 on L-LTP, which requires new protein synthesis and is important for the process of chronic pain, has not been investigated. Here we tested the effects of NB001 on the ACC L-LTP and found that bath application of NB001 (0.1 μM) totally blocked the induction of L-LTP and recruitment of cortical circuitry without affecting basal excitatory transmission. In contrast, gabapentin, a widely used analgesic drug for neuropathic pain, did not block the induction of L-LTP and circuitry recruitment even at a high concentration (100 μM). Gabapentin non-selectively decreased basal synaptic transmission. Our results provide strong evidence that the selective AC1 inhibitor NB001 can be used to inhibit pain-related cortical L-LTP without affecting basal synaptic transmission. It also provides basic mechanisms for possible side effects of gabapentin in the central nervous system and its ineffectiveness in some patients with neuropathic pain.read more
Citations
More filters
Journal ArticleDOI
Synaptic plasticity in the anterior cingulate cortex in acute and chronic pain
TL;DR: Increasing evidence from rodent studies that ACC activation contributes to chronic pain states is discussed and several forms of synaptic plasticity that may underlie this effect are described.
Journal ArticleDOI
Neural Mechanisms Underlying Anxiety-Chronic Pain Interactions.
TL;DR: It is proposed chronic anxiety triggered by injury or chronic pain is mediated through presynaptic long-term potentiation in the anterior cingulate cortex (ACC), a key cortical region for pain perception and NMDA receptor-dependent postsynaptic LTP plays a more important role in behavioral sensitization in chronic pain.
Journal ArticleDOI
A new perspective on the anterior cingulate cortex and affective pain.
Xiao Xiao,Yu-Qiu Zhang +1 more
TL;DR: The anterior cingulate cortex (ACC) is not only necessary but also sufficient for pain‐related negative emotion and the important advances within the optogenetic filed provide new opportunities to deepen and expand the understanding of the affective pain.
Journal ArticleDOI
Impaired presynaptic long-term potentiation in the anterior cingulate cortex of Fmr1 knock-out mice.
TL;DR: It is demonstrated that FMRP plays an important role in pre-LTP in the adult mouse ACC, and loss of this pre- LTP may explain some of the behavioral deficits in Fmr1 KO mice.
Journal ArticleDOI
NMDA Receptor Dependent Long-term Potentiation in Chronic Pain.
TL;DR: Behavioral, genetic and pharmacological studies show that inhibiting or reducing NMDAR LTP produced analgesic effects in animal models of chronic pain.
References
More filters
Journal ArticleDOI
A synaptic model of memory: long-term potentiation in the hippocampus
TL;DR: The best understood form of long-term potentiation is induced by the activation of the N-methyl-d-aspartate receptor complex, which allows electrical events at the postsynaptic membrane to be transduced into chemical signals which, in turn, are thought to activate both pre- and post Synaptic mechanisms to generate a persistent increase in synaptic strength.
Journal ArticleDOI
The Molecular Biology of Memory Storage: A Dialogue Between Genes and Synapses
TL;DR: This book aims to investigate elementary forms of learning and memory at a cellular molecular level—as specific molecular activities within identified nerve cells withinidentified nerve cells.
Journal ArticleDOI
Neuropathic Pain: A Maladaptive Response of the Nervous System to Damage
TL;DR: Treatment needs to move from merely suppressing symptoms to a disease-modifying strategy aimed at both preventing maladaptive plasticity and reducing intrinsic risk.
Journal ArticleDOI
Genetic Demonstration of a Role for PKA in the Late Phase of LTP and in Hippocampus-Based Long-Term Memory
Ted Abel,Peter V. Nguyen,Mark Barad,Thomas A.S Deuel,Eric R. Kandel,Roussoudan Bourtchouladze +5 more
TL;DR: In transgenic mice that express R(AB), an inhibitory form of the regulatory subunit of PKA, only in the hippocampus and other forebrain regions, hippocampal PKA activity was reduced, and L-LTP was significantly decreased in area CA1, without affecting basal synaptic transmission or the early phase of LTP.
Journal ArticleDOI
Effects of cAMP simulate a late stage of LTP in hippocampal CA1 neurons
TL;DR: Activation of PKA may be a component of the mechanism that generates L-LTP, and analogs of cAMP induced a potentiation that blocked naturally induced L- LTP, which was blocked by inhibitors of protein synthesis.
Related Papers (5)
Alleviating Neuropathic Pain Hypersensitivity by Inhibiting PKMζ in the Anterior Cingulate Cortex
Xiang-Yao Li,Xiang-Yao Li,Hyoung-Gon Ko,Tao Chen,Tao Chen,Giannina Descalzi,Kohei Koga,Hansen Wang,Susan S. Kim,Yuze Shang,Chuljung Kwak,Soowon Park,Jaehoon Shim,Jaehoon Shim,Kyungmin Lee,Kyungmin Lee,Graham L. Collingridge,Graham L. Collingridge,Bong-Kiun Kaang,Bong-Kiun Kaang,Min Zhuo,Min Zhuo +21 more