title: Enhanced excitability in the infralimbic cortex produces anxiety-like behaviors.
abstract: The medial prefrontal cortex (mPFC) has been implicated in modulating anxiety. However, it is unknown whether excitatory or inhibitory neurotransmission in the infralimbic (IL) subregion of the mPFC underlies the pathology of anxiety-related behavior. To address this issue, we infused the GABAA receptor (GABAAR) antagonist bicuculline to temporarily activate the IL cortex. IL cortex activation decreased the time spent in the center area in the open field test, decreased exploration of the open-arms in the elevated plus maze test, and increased the latency to bite food in the novelty-suppressed feeding test. These findings substantiate the GABAergic system's role in anxiety-related behaviors. IL cortex inactivation with the AMPA receptor (AMPAR) antagonist CNQX produced opposite, anxiolytic effects. However, infusion of the NMDA receptor (NMDAR) antagonist AP5 into the IL cortex had no significant effect. Additionally, we did not observe motor activity deficits or appetite deficits following inhibition of GABAergic or glutamatergic neurotransmission. Interestingly, we found parallel and corresponding electrophysiological changes in anxious mice; compared to mice with relatively low anxiety, the relatively high anxiety mice exhibited smaller evoked inhibitory postsynaptic currents (eIPSCs) and larger AMPA-mediated evoked excitatory postsynaptic currents (eEPSCs) in pyramidal neurons in the IL cortex. The changes of eIPSCs and eEPSCs were due to presynaptic mechanisms. Our results suggest that imbalances of neurotransmission in the IL cortex may cause a net increase in excitatory inputs onto pyramidal neurons, which may underlie the pathogenic mechanism of anxiety disorders.
authors: Department of Neurobiology, School of Basic Medical Sciences, Southern Medical University, Guangzhou 510515, China.
authors: Lin-Lin
authors: LL
authors: Bi
authors: Jue
authors: J
authors: Wang
authors: Zheng-Yi
authors: ZY
authors: Luo
authors: Shan-Ping
authors: SP
authors: Chen
authors: Fei
authors: F
authors: Geng
authors: Yi-hua
authors: YH
authors: Chen
authors: Shu-Ji
authors: SJ
authors: Li
authors: Chun-hua
authors: CH
authors: Yuan
authors: Song
authors: S
authors: Lin
authors: Tian-Ming
authors: TM
authors: Gao
mesh_terms: D018750:6-Cyano-7-nitroquinoxaline-2,3-dione / Q000494:pharmacology / Q000627:therapeutic use; D000818:Animals; D000831:Animals, Newborn; D001007:Anxiety / Q000139:chemically induced / Q000188:drug therapy / Q000473:pathology*; D001640:Bicuculline / Q000633:toxicity; D004195:Disease Models, Animal; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology / Q000627:therapeutic use; D019706:Excitatory Postsynaptic Potentials / Q000187:drug effects / Q000502:physiology*; D005106:Exploratory Behavior / Q000187:drug effects; D058787:GABA-A Receptor Antagonists / Q000633:toxicity; D066298:In Vitro Techniques; D053444:Inhibitory Postsynaptic Potentials / Q000187:drug effects; D007276:Injections, Intraventricular; D008297:Male; D018782:Maze Learning / Q000187:drug effects; D051379:Mice; D008810:Mice, Inbred C57BL; D018408:Patch-Clamp Techniques; D017397:Prefrontal Cortex / Q000187:drug effects / Q000503:physiopathology*
chemical_list: D018691:Excitatory Amino Acid Antagonists; D058787:GABA-A Receptor Antagonists; D018750:6-Cyano-7-nitroquinoxaline-2,3-dione; D001640:Bicuculline