Rescue of Impaired mGluR5-Driven Endocannabinoid Signaling Restores Prefrontal Cortical Output to Inhibit Pain in Arthritic Rats

The Journal of Neuroscience : the Official Journal of the Society for Neuroscience
Takaki KiritoshiVolker Neugebauer

Abstract

The medial prefrontal cortex (mPFC) serves executive functions that are impaired in neuropsychiatric disorders and pain. Underlying mechanisms remain to be determined. Here we advance the novel concept that metabotropic glutamate receptor 5 (mGluR5) fails to engage endocannabinoid (2-AG) signaling to overcome abnormal synaptic inhibition in pain, but restoring endocannabinoid signaling allows mGluR5 to increase mPFC output hence inhibit pain behaviors and mitigate cognitive deficits. Whole-cell patch-clamp recordings were made from layer V pyramidal cells in the infralimbic mPFC in rat brain slices. Electrical and optogenetic stimulations were used to analyze amygdala-driven mPFC activity. A selective mGluR5 activator (VU0360172) increased pyramidal output through an endocannabinoid-dependent mechanism because intracellular inhibition of the major 2-AG synthesizing enzyme diacylglycerol lipase or blockade of CB1 receptors abolished the facilitatory effect of VU0360172. In an arthritis pain model mGluR5 activation failed to overcome abnormal synaptic inhibition and increase pyramidal output. mGluR5 function was rescued by restoring 2-AG-CB1 signaling with a CB1 agonist (ACEA) or inhibitors of postsynaptic 2-AG hydrolyzing enzyme...Continue Reading

Citations

Jun 20, 2017·Neuropharmacology·Stephen G WoodhamsVolker Neugebauer
Dec 7, 2016·Molecular Pain·David Gomez-Varela, Manuela Schmidt
Jul 27, 2017·Neuropsychopharmacology : Official Publication of the American College of Neuropsychopharmacology·Matthew N HillSachin Patel
Jan 6, 2018·Pain Research & Management : the Journal of the Canadian Pain Society = Journal De La Société Canadienne Pour Le Traitement De La Douleur·Jeremy M Thompson, Volker Neugebauer
Nov 11, 2017·British Journal of Pharmacology·Rafael MaldonadoDavid Cabañero
Sep 14, 2019·The International Journal of Neuroscience·Yiling QianYanqiang Li
Jun 8, 2018·Molecular Neurobiology·Wei-Yi OngDeron R Herr
Aug 29, 2018·Frontiers in Cellular Neuroscience·Haocheng ZhouJing Wang
Jun 13, 2017·Frontiers in Cellular Neuroscience·Erik MartinezJing Wang
Oct 26, 2018·Frontiers in Molecular Neuroscience·Mariacristina MazzitelliVolker Neugebauer
Dec 14, 2018·Frontiers in Pharmacology·Sonja VučkovićMilica Prostran
Jun 12, 2020·Physiological Reviews·Rohini Kuner, Thomas Kuner
Jan 15, 2020·Current Neuropharmacology·Mortimer Mamelak
Jan 30, 2021·Trends in Cognitive Sciences·Caroline E PhelpsFrank Porreca
Oct 15, 2019·Psychosomatic Medicine·Louise Urien, Jing Wang
Mar 20, 2020·Neuropharmacology·Volker NeugebauerFrank Porreca
Mar 28, 2018·Neuropharmacology·Dominic A GioiaJohn J Woodward
Mar 30, 2020·Current Biology : CB·Amrita SinghJing Wang
May 3, 2018·Cell Reports·Jahrane DaleJing Wang
Sep 5, 2019·Journal of Nuclear Medicine : Official Publication, Society of Nuclear Medicine·Jenny CeccariniKoen Van Laere
Jun 23, 2021·Nature Biomedical Engineering·Qiaosheng ZhangJing Wang

❮ Previous
Next ❯

Related Concepts

Related Feeds

Amygdala: Sensory Processes

Amygdalae, nuclei clusters located in the temporal lobe of the brain, play a role in memory, emotional responses, and decision-making. Here is the latest research on sensory processes in the amygdala.

Amygdala and Midbrain Dopamine

The midbrain dopamine system is widely studied for its involvement in emotional and motivational behavior. Some of these neurons receive information from the amygdala and project throughout the cortex. When the circuit and transmission of dopamine is disrupted symptoms may present. Here is the latest research on the amygdala and midbrain dopamine.