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Dematuration in the adult brain

開催日 2014/9/12
時間 15:00 - 17:00
会場 Room D(503)
Chairperson(s) 小林 克典 / Katsunori Kobayashi (日本医科大学大学院医学研究科薬理学分野 / Department of Pharmacology, Nippon Medical School, Japan)
宮川 剛 / Tsuyoshi Miyakawa (藤田保健衛生大学 総合医科学研究所 システム医科学研究部門 / Division of Systems Medical Science, Institute for Comprehensive Medical Science, Fujita Health University, Japan)

Activity-dependent regulation of the functional maturation of adult hippocampal neurons

  • S2-D-1-3
  • 小林 克典 / Katsunori Kobayashi:1 
  • 1:日本医科大・医・薬理 / Dept. Pharmacol, Nippon Med.Sch., Tokyo, Japan 

The altered state of neuronal maturation has been implicated in the pathophysiological basis of neuropsychiatric disorders and mechanism of action of antidepressant drugs. We have shown that the serotonergic antidepressant fluoxetine can reverse the state of maturation of the granule cells in the dentate gyrus of the adult mouse hippocampus, indicating modifiable nature of the state of neuronal maturation in adults. This dematuration causes a marked change in functional properties of granule cells, including enhanced excitatory synaptic input, increased somatic excitability and reduced frequency facilitation at the output synapse, which may underlie therapeutic effects and/or adverse effects of antidepressant treatments. To investigate whether the granule cell dematuration is induced by other antidepressant treatments, we examined the effect of electroconvulsive stimulation (ECS), an animal model of electroconvulsive therapy for depression, on the dentate granule cells in adult mice. We found that ECS causes robust and sustained changes in the granule cell functions that are indistinguishable from those induced by fluoxetine, indicating that ECS can induce granule cell dematuration. ECS-induced dematruation was accompanied by enhanced synaptic activation of the granule cells and a change in synaptic excitation/inhibition balance toward excitation. An augmentation of GABAergic inhibition by the benzodiazepine diazepam selectively prevented the maintenance phase, leaving the initial induction phase intact. These results indicate that neuronal activity plays an essential role in regulating the state of functional maturation of neurons in the adult brain. Our finding imply potential importance of controlling neuronal excitation in antidepressant treatments and also suggests a novel approach to treat neuronal dysfunction in neuropsychiatric disorders via regulation of neuronal activity.

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