Cortical kainate receptors and behavioral anxiety.

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Abstract

The study of glutamatergic synapses mainly focuses on the memory-related hippocampus. Recent studies in the cortical areas such as the anterior cingulate cortex (ACC) show that excitatory synapses can undergo long-term plastic changes in adult animals. Long-term potentiation (LTP) of cortical synapses may play important roles in chronic pain and anxiety. In addition to NMDA and AMPA receptors, kainate (KA) receptors have been found to play roles in synaptic transmission, regulation and presynaptic forms of LTP. In this brief review, I will summarize the new progress made on KA receptors, and propose that ACC synapses may provide a good synaptic model for understanding cortical mechanism for behavioral anxiety, and its related emotional disorders.

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Pain and emotion interactions in subregions of the cingulate gyrus.

Brent Vogt (2005)

Acute pain and emotion are processed in two forebrain networks, and the cingulate cortex is involved in both. Although Brodmann's cingulate gyrus had two divisions and was not based on any functional criteria, functional imaging studies still use this model. However, recent cytoarchitectural studies of the cingulate gyrus support a four-region model, with subregions, that is based on connections and qualitatively unique functions. Although the activity evoked by pain and emotion has been widely reported, some view them as emergent products of the brain rather than of small aggregates of neurons. Here, we assess pain and emotion in each cingulate subregion, and assess whether pain is co-localized with negative affect. Amazingly, these activation patterns do not simply overlap.

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Synaptic plasticity in the anterior cingulate cortex in acute and chronic pain.

Tim Bliss, Graham L. Collingridge, Bong-Kiun Kaang … (2016)

The anterior cingulate cortex (ACC) is activated in both acute and chronic pain. In this Review, we discuss increasing evidence from rodent studies that ACC activation contributes to chronic pain states and describe several forms of synaptic plasticity that may underlie this effect. In particular, one form of long-term potentiation (LTP) in the ACC, which is triggered by the activation of NMDA receptors and expressed by an increase in AMPA-receptor function, sustains the affective component of the pain state. Another form of LTP in the ACC, which is triggered by the activation of kainate receptors and expressed by an increase in glutamate release, may contribute to pain-related anxiety.

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Coexistence of two forms of LTP in ACC provides a synaptic mechanism for the interactions between anxiety and chronic pain.

Kohei Koga, Giannina Descalzi, Tao Chen … (2015)

Chronic pain can lead to anxiety and anxiety can enhance the sensation of pain. Unfortunately, little is known about the synaptic mechanisms that mediate these re-enforcing interactions. Here we characterized two forms of long-term potentiation (LTP) in the anterior cingulate cortex (ACC); a presynaptic form (pre-LTP) that requires kainate receptors and a postsynaptic form (post-LTP) that requires N-methyl-D-aspartate receptors. Pre-LTP also involves adenylyl cyclase and protein kinase A and is expressed via a mechanism involving hyperpolarization-activated cyclic nucleotide-gated (HCN) channels. Interestingly, chronic pain and anxiety both result in selective occlusion of pre-LTP. Significantly, microinjection of the HCN blocker ZD7288 into the ACC in vivo produces both anxiolytic and analgesic effects. Our results provide a mechanism by which two forms of LTP in the ACC may converge to mediate the interaction between anxiety and chronic pain.

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PubMed ID:: 28521778

PMC ID:: 5437545

DOI:: 10.1186/s13041-017-0297-8

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Cortical kainate receptors and behavioral anxiety.

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Most cited references 41

Pain and emotion interactions in subregions of the cingulate gyrus.

Synaptic plasticity in the anterior cingulate cortex in acute and chronic pain.

Coexistence of two forms of LTP in ACC provides a synaptic mechanism for the interactions between anxiety and chronic pain.

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