Enhanced presynaptic neurotransmitter release in the anterior cingulate cortex of mice with chronic pain.
The anterior cingulate cortex (ACC) is a forebrain structure known for its roles in learning and memory. Recent studies show that painful stimuli activate the prefrontal cortex and that brain chemistry is altered in this area in patients with chronic pain. Components of the CNS that are involved in pain transmission and modulation, from the spinal cord to the ACC, are very plastic and undergo rapid and long-term changes after injury. Patients suffering from chronic pain often complain of memory and concentration difficulties, but little is known about the neural circuitry underlying these deficits. To address this question, we analyzed synaptic transmission in the ACC from mice with chronic pain induced by hindpaw injection of complete Freund's adjuvant (CFA). In vitro whole-cell patch-clamp recordings revealed a significant enhancement in neurotransmitter release probability in ACC synapses from mice with chronic pain. Trace fear memory, which requires sustained attention and the activity of the ACC, was impaired in CFA-injected mice. Using knock-out mice, we found that calmodulin-stimulated adenylyl cyclases, AC1 and/or AC8, were crucial in mediating the long-lasting enhanced presynaptic transmitter release in the ACC of mice with chronic pain. Our findings provide strong evidence that presynaptic alterations caused by peripheral inflammation contribute to memory impairments after injury.
Zhao
Ming-Gao
MG
Department of Physiology, Faculty of Medicine, and Centre for the Study of Pain, University of Toronto, Toronto, Ontario, Canada M5S 1A8.
Ko
Shanelle W
SW
Wu
Long-Jun
LJ
Toyoda
Hiroki
H
Xu
Hui
H
Quan
Jessica
J
Li
Jianguo
J
Jia
Yongheng
Y
Ren
Ming
M
Xu
Zao C
ZC
Zhuo
Min
M
D000262:Adenylyl Cyclases / Q000172:deficiency; D000818:Animals; D002908:Chronic Disease; D004558:Electric Stimulation / Q000379:methods; D005239:Fear; D005620:Freund's Adjuvant / Q000008:administration & dosage / Q000494:pharmacology; D006179:Gyrus Cinguli / Q000378:metabolism*; D066298:In Vitro Techniques; D007267:Injections; D008297:Male; D008568:Memory / Q000187:drug effects; D051379:Mice; D018345:Mice, Knockout; D018377:Neurotransmitter Agents / Q000378:metabolism*; D010146:Pain / Q000378:metabolism* / Q000523:psychology; D017729:Presynaptic Terminals / Q000378:metabolism*; D011336:Probability; D009435:Synaptic Transmission / Q000187:drug effects
D018377:Neurotransmitter Agents; D005620:Freund's Adjuvant; D000262:Adenylyl Cyclases