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HCN channels in the hippocampus regulate active coping behavior
Author(s) -
Fisher Daniel W.,
Han Ye,
Lyman Kyle A.,
Heuermann Robert J.,
Bean Linda A.,
Ybarra Natividad,
Foote Kendall M.,
Dong Hongxin,
Nicholson Daniel A.,
Chetkovich Dane M.
Publication year - 2018
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1111/jnc.14539
Subject(s) - coping (psychology) , gene knockdown , neuroscience , psychology , antidepressant , chemistry , clinical psychology , hippocampus , biochemistry , gene
Active coping is an adaptive stress response that improves outcomes in medical and neuropsychiatric diseases. To date, most research into coping style has focused on neurotransmitter activity and little is known about the intrinsic excitability of neurons in the associated brain regions that facilitate coping. Previous studies have shown that HCN channels regulate neuronal excitability in pyramidal cells and that HCN channel current (I h ) in the CA 1 area increases with chronic mild stress. Reduction of I h in the CA 1 area leads to antidepressant‐like behavior, and this region has been implicated in the regulation of coping style. We hypothesized that the antidepressant‐like behavior achieved with CA 1 knockdown of I h is accompanied by increases in active coping. In this report, we found that global loss of TRIP 8b, a necessary subunit for proper HCN channel localization in pyramidal cells, led to active coping behavior in numerous assays specific to coping style. We next employed a viral strategy using a dominant negative TRIP 8b isoform to alter coping behavior by reducing HCN channel expression. This approach led to a robust reduction in I h in CA 1 pyramidal neurons and an increase in active coping. Together, these results establish that changes in HCN channel function in CA 1 influences coping style.