Publications (28) View all
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Article: Erasing fear memories - key receptor and essential timeframe discovered.
Acta Pharmacologica Sinica 01/2011; 32(1):1-2. · 1.95 Impact Factor -
Article: Effects of ipsilateral cerebellum ablation on acquisition and retention of classically conditioned eyeblink responses in rats.
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ABSTRACT: The ipsilateral cerebellum to the trained eye has been reported to be essential for acquisition and retention of the conditioned response (CR) in rabbit eyeblink conditioning. Although pharmacological studies have suggested its important roles in other species too, to what degree does eyeblink conditioning in rats depend on the ipsilateral cerebellum is not clear. In this work, we ablated the ipsilateral cerebellum in rats before or after conditioning to examine its roles in acquisition and retention of the CR. In the first experiment, rats received ablation of the ipsilateral cerebellum and recovered for more than 3 weeks. They then underwent eyeblink conditioning for 7 days with a tone and a periorbital electrical shock. Consistent with other previous reports, hemicerebellectomized rats showed significant impairment compared to sham-lesioned rats. However, the hemicerebellectomized rats acquired CRs to some degree, and the acquired CR showed adaptive timing. In the second experiment, rats received the hemicerebellectomy after acquiring CR by 7 days of conditioning in a delay paradigm. After more than 3 weeks of recovery, they were again conditioned in a delay paradigm. Rats with ipsilateral cerebellar lesions showed severe impairment in retention of the pre-acquired CR; however, they reacquired CR to some degree during the subsequent reconditioning sessions. These results suggest that the ipsilateral cerebellum plays an important role in rat eyeblink conditioning as well but that other brain regions can partially compensate for its removal.Neuroscience Letters 02/2010; 472(2):148-52. · 2.11 Impact Factor -
Article: Dual involvement of G-substrate in motor learning revealed by gene deletion.
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ABSTRACT: In this study, we generated mice lacking the gene for G-substrate, a specific substrate for cGMP-dependent protein kinase uniquely located in cerebellar Purkinje cells, and explored their specific functional deficits. G-substrate-deficient Purkinje cells in slices obtained at postnatal weeks (PWs) 10-15 maintained electrophysiological properties essentially similar to those from WT littermates. Conjunction of parallel fiber stimulation and depolarizing pulses induced long-term depression (LTD) normally. At younger ages, however, LTD attenuated temporarily at PW6 and recovered thereafter. In parallel with LTD, short-term (1 h) adaptation of optokinetic eye movement response (OKR) temporarily diminished at PW6. Young adult G-substrate knockout mice tested at PW12 exhibited no significant differences from their WT littermates in terms of brain structure, general behavior, locomotor behavior on a rotor rod or treadmill, eyeblink conditioning, dynamic characteristics of OKR, or short-term OKR adaptation. One unique change detected was a modest but significant attenuation in the long-term (5 days) adaptation of OKR. The present results support the concept that LTD is causal to short-term adaptation and reveal the dual functional involvement of G-substrate in neuronal mechanisms of the cerebellum for both short-term and long-term adaptation.Proceedings of the National Academy of Sciences 03/2009; 106(9):3525-30. · 9.68 Impact Factor -
Article: Orexins increase mRNA expressions of neurotrophin-3 in rat primary cortical neuron cultures.
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ABSTRACT: Orexins and melanin-concentrating hormone (MCH) as orexigenic neuropeptides are present in the lateral hypothalamus, and their receptors are distributed in the cerebral cortex and hippocampus. In the present study, the regulatory effects of orexin-A, orexin-B and MCH on neurotrophin-3 (NT-3) and brain-derived neurotrophic factor (BDNF) expressions were examined in primary cortical neuron cultures using quantitative real-time PCR. Both orexin-A and orexin-B on 6-day exposure significantly increased the NT-3 mRNA at concentrations of 0.01, 0.1 and 1microM. Orexin-A and B at 1microM led to an increase of twofold or more over the control. However, no such NT-s mRNA increase occurred with exposure to MCH at the same concentrations as orexins. The mRNA expression of BDNF was significantly increased only by orexin-B at 1microM. These findings suggest that orexins, but not MCH, may be an inducer of NT-3 in the cerebral cortex.Neuroscience Letters 12/2008; 450(2):132-5. · 2.11 Impact Factor -
Article: Orexin decreases mRNA expressions of NMDA and AMPA receptor subunits in rat primary neuron cultures.
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ABSTRACT: Orexin is one of the orexigenic neuropeptides in the hypothalamus. Orexin neurons in the lateral hypothalamus (LH) project into the cerebral cortex and hippocampus in which the receptors are distributed in high concentrations. Therefore, to elucidate the actions of orexin in the cerebral cortex, we examined its effects on the mRNA expressions of N-methyl-d-aspartate (NMDA) receptor subunits (NR1, NR2A, NR2B) and alpha-amino-3-hydroxy-5-methylisoxazole-4-propionate (AMPA) receptor subunits (GluR1, GluR2) following 6-day application of orexin-A or orexin-B to rat primary cortical neuron cultures. The mRNAs of NR1 and NR2A subunits were significantly decreased by orexin-A and orexin-B at concentrations over 0.1 microM and 0.01 microM, respectively. The mRNA expression of NR2B subunit was also significantly decreased by orexin-A and orexin-B only at the concentration of 1 microM. Moreover, orexin-A and orexin-B at concentrations over 0.01 microM significantly decreased the mRNA expressions of AMPA receptor subunits, GluR1 and GluR2. The present study demonstrated that orexins significantly suppressed RNA expressions of NMDA and AMPA receptor subunits in cortical neuron cultures, suggesting that orexin may regulate the higher functions of the cerebral cortex as well as be involved in energy regulation in the hypothalamus.Peptides 06/2008; 29(9):1582-7. · 2.43 Impact Factor
