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

K Koga, G Descalzi, T Chen, HG Ko, J Lu, S Li, J Son… - Neuron, 2015 - cell.com
K Koga, G Descalzi, T Chen, HG Ko, J Lu, S Li, J Son, TH Kim, C Kwak, RL Huganir, M Zhao
Neuron, 2015cell.com
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 …
Summary
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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