Increase in excitability of hippocampal neurons during novelty-induced hyperlocomotion in dopamine-deficient mice
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Increase in excitability of hippocampal neurons during novelty-induced hyperlocomotion in dopamine-deficient mice Masayo Fujita1†, Yukiko Ochiai1,2†, Taishi-Clark Takeda1, Yoko Hagino1, Kazuto Kobayashi3 and Kazutaka Ikeda1* Abstract Dopamine is involved in many important brain functions, including voluntary motor movement. Dysfunction of the dopaminergic system can induce motor impairments, including Parkinson’s disease. We previously found that dopaminedeficient (DD) mice became hyperactive in a novel environment 72 h after the last injection of L-3,4-dihydroxyphenylalanine (L-DOPA) when dopamine was almost completely depleted. In the present study, we investigated neuronal activity in hippocampal subregions during hyperactivity by measuring Fos expression levels using immunohistochemistry. Dopaminedeficient mice were maintained on daily intraperitoneal injections of 50 mg/kg L-DOPA. Seventy-two hours after the last LDOPA injection, DD mice were exposed to a novel environment for 1, 2, or 4 h, and then brains were collected. In wildtype mice, the number of Fos-immunopositive neurons significantly increased in the hippocampal CA1 region after 1 h of exposure to the novel environment and then decreased. In DD mice, the number of Fos-immunopositive neurons gradually increased and then significantly increased after 4 h of exposure to the novel environment. The number of Fosimmunopositive neurons also significantly increased in the CA3 region and dentate gyrus in DD mice after 4 h of exposure to the novel environment. These results indicate that the delayed and prolonged excitation of hippocampal neurons in the CA1, CA3, and dentate gyrus that is caused by dopamine depletion might be involved in hyperactivity in DD mice. Dopamine is involved in many important brain functions, including voluntary motor movement. Dysfunction of the dopaminergic system can induce motor impairments, including Parkinson’s disease. Therefore, locomotor activity is thought to be correlated with dopamine levels. We previously found that dopamine-deficient (DD) mice became hyperactive in a novel environment when brain dopamine levels were almost completely depleted [1], although DD mice were hypoactive in their home cage [2]. Dopamine deficiency in mice is induced * Correspondence: [email protected] † Masayo Fujita and Yukiko Ochiai contributed equally to this work. 1 Department of Psychiatry and Behavioral Sciences, Addictive Substance Project, Tokyo Metropolitan Institute of Medical Science, 2-1-6 Kamikitazawa, Setagaya-ku, Tokyo 156-8506, Japan Full list of author information is available at the end of the article
by knockout of the tyrosine hydroxylase (TH) gene, with the concomitant restoration of TH expression under control of the dopamine β-hydroxylase (DBH) promoter to prevent the loss of epinephrine and norepinephrine [3]. Another research group also established a different DD mouse model and studied their behaviors. Their studies showed that DD mice exhibited deficiencies in motivated behavior, but t
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