title: Gap junctions in the ventral hippocampal-medial prefrontal pathway are involved in anxiety regulation.
abstract: Anxiety disorders are highly prevalent but little is known about their underlying mechanisms. Gap junctions exist in brain regions important for anxiety regulation, such as the ventral hippocampus (vHIP) and mPFC, but their functions in these areas have not been investigated. Using pharmacological blockade of neuronal gap junctions combined with electrophysiological recordings, we found that gap junctions play a role in theta rhythm in the vHIP and mPFC of adult mice. Bilateral infusion of neuronal gap junction blockers into the vHIP decreased anxiety-like behavior on the elevated plus maze and open field. Similar anxiolytic effects were observed with unilateral infusion of these drugs into the vHIP combined with contralateral infusion into the mPFC. No change in anxious behavior was observed with gap junction blockade in the unilateral vHIP alone or in the bilateral dorsal HIP. Since physical exercise is known to reduce anxiety, we examined the effects of long-term running on the expression of the neuronal gap junction protein connexin-36 among inhibitory interneurons and found a reduction in the vHIP. Despite this change, we observed no alteration in theta frequency or power in long-term runners. Collectively, these findings suggest that neuronal gap junctions in the vHIP-mPFC pathway are important for theta rhythm and anxiety regulation under sedentary conditions but that additional mechanisms are likely involved in running-induced reduction in anxiety.
authors.affiliation: Departments of Psychology and.
authors.forename: Timothy J
authors.initials: TJ
authors.lastname: Schoenfeld
authors.affiliation: Molecular Biology and Princeton Neuroscience Institute, Princeton University, Princeton, New Jersey 08544.
authors.forename: Alexander D
authors.identifier: http://orcid.org/0000-0001-8119-1213
authors.initials: AD
authors.lastname: Kloth
authors.affiliation: Departments of Psychology and.
authors.forename: Brian
authors.initials: B
authors.lastname: Hsueh
authors.affiliation: Departments of Psychology and.
authors.forename: Matthew B
authors.initials: MB
authors.lastname: Runkle
authors.affiliation: Departments of Psychology and.
authors.forename: Gary A
authors.initials: GA
authors.lastname: Kane
authors.affiliation: Molecular Biology and Princeton Neuroscience Institute, Princeton University, Princeton, New Jersey 08544.
authors.forename: Samuel S-H
authors.initials: SS
authors.lastname: Wang
authors.affiliation: Departments of Psychology and goulde@princeton.edu.
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Gould
mesh_terms: D000818:Animals; D001007:Anxiety / Q000503:physiopathology*; D001522:Behavior, Animal / Q000502:physiology; D017630:Connexins / Q000235:genetics / Q000502:physiology; D004569:Electroencephalography; D017629:Gap Junctions / Q000502:physiology*; D006624:Hippocampus / Q000502:physiology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009434:Neural Pathways / Q000502:physiology; D017397:Prefrontal Cortex / Q000502:physiology*; D012420:Running / Q000523:psychology; D013826:Theta Rhythm / Q000187:drug effects; D000097004:Gap Junction delta-2 Protein
chemical_list: D017630:Connexins; D000097004:Gap Junction delta-2 Protein
keywords: anxiety; connexin; gap junctions; medial prefrontal cortex; theta rhythm; ventral hippocampus