title: Increase in cortical pyramidal cell excitability accompanies depression-like behavior in mice: a transcranial magnetic stimulation study.
abstract: Clinical evidence suggests that cortical excitability is increased in depressives. We investigated its cellular basis in a mouse model of depression. In a modified version of forced swimming (FS), mice were initially forced to swim for 5 consecutive days and then were treated daily with repetitive transcranial magnetic stimulation (rTMS) or sham treatment for the following 4 weeks without swimming. On day 2 through day 5, the mice manifested depression-like behaviors. The next and last FS was performed 4 weeks later, which revealed a 4 week maintenance of depression-like behavior in the sham mice. In slices from the sham controls, excitability in cingulate cortex pyramidal cells was elevated in terms of membrane potential and frequencies of spikes evoked by current injection. Depolarized resting potential was shown to depend on suppression of large conductance calcium-activated potassium (BK) channels. This BK channel suppression was confirmed by measuring spike width, which depends on BK channels. Chronic rTMS treatment during the 4 week period significantly reduced the depression-like behavior. In slices obtained from the rTMS mice, normal excitability and BK channel activity were recovered. Expression of a scaffold protein Homer1a was reduced by the FS and reversed by rTMS in the cingulate cortex. Similar recovery in the same behavioral, electrophysiological, and biochemical features was observed after chronic imipramine treatment. The present study demonstrated that manifestation and disappearance of depression-like behavior are in parallel with increase and decrease in cortical neuronal excitability in mice and suggested that regulation of BK channels by Homer1a is involved in this parallelism.
authors.affiliation: Department of Physiology and Medical Research Institute, Kanazawa Medical University, Ishikawa 920-0293, Japan.
authors.forename: Peng
authors.initials: P
authors.lastname: Sun
authors.forename: Furong
authors.initials: F
authors.lastname: Wang
authors.forename: Li
authors.initials: L
authors.lastname: Wang
authors.forename: Yu
authors.initials: Y
authors.lastname: Zhang
authors.forename: Ryo
authors.initials: R
authors.lastname: Yamamoto
authors.forename: Tokio
authors.initials: T
authors.lastname: Sugai
authors.forename: Qing
authors.initials: Q
authors.lastname: Zhang
authors.forename: Zhengda
authors.initials: Z
authors.lastname: Wang
authors.forename: Nobuo
authors.initials: N
authors.lastname: Kato
mesh_terms: D000200:Action Potentials / Q000187:drug effects / Q000502:physiology; D000704:Analysis of Variance; D000818:Animals; D000929:Antidepressive Agents, Tricyclic / Q000494:pharmacology; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism; D002540:Cerebral Cortex / Q000378:metabolism / Q000473:pathology*; D003863:Depression / Q000473:pathology* / Q000628:therapy*; D004195:Disease Models, Animal; D004558:Electric Stimulation; D004594:Electrophysiology; D005786:Gene Expression Regulation / Q000187:drug effects / Q000502:physiology; D000072233:Homer Scaffolding Proteins; D007099:Imipramine / Q000494:pharmacology; D046353:Immobility Response, Tonic / Q000187:drug effects / Q000502:physiology; D066298:In Vitro Techniques; D051036:Large-Conductance Calcium-Activated Potassium Channels / Q000235:genetics / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D017966:Pyramidal Cells / Q000503:physiopathology*; D020127:Recovery of Function / Q000187:drug effects; D013550:Swimming / Q000523:psychology; D013997:Time Factors; D050781:Transcranial Magnetic Stimulation / Q000379:methods*
chemical_list: D000929:Antidepressive Agents, Tricyclic; D002352:Carrier Proteins; D000072233:Homer Scaffolding Proteins; D051036:Large-Conductance Calcium-Activated Potassium Channels; D007099:Imipramine
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