Effects of coaction of dopaminergic modulation and inward rectifying potassium current inactivation on the biophysical properties of medium spiny neurons

Abstracts in mammalian tissue cells. To further understand its role in autophagy, we produced antibody to Atg9A and examined its distribution. The distribution of the protein was ubiquitous in various mouse tissues, but its protein amount was the highest in brain tissue. Immunohistochemical observations showed that immunosignals for Atg9 was detected in the trans-Golgi network, endosomes, and lysosomes of large neurons such as cerebral cortical neurons and cerebellar Purkinje cells. The immunosignals were also found in part in rough endoplasmic reticulum, while they were also found in axons but not in dendrites. doi:10.1016/j.neures.2009.09.660

P1-p19 Increased regional brain temperature by stimulus-induced neuronal activation Chizuko Inui-Yamamoto 1,5 , Tsuyoshi Shimura 2 , Akitoshi Seiyama 3,5 , Yoshichika Yoshioka 4,5 , Izumi Ohzawa 1,5 1

Grad. Sch. Front Biosci., Osaka University, Osaka, Japan; 2 Behav Physiol., Grad. Sch. Human Sci., Osaka University, Osaka, Japan; 3 Front Health Sci., Grad. Sch. Med., Kyoto University, Kyoto, Japan; 4 Immun Front Res. Center, Osaka University, Osaka, Japan; 5 CREST, JST, Japan

Regional brain temperature (rBT) in the homeotherm may be determined by the local heat production due to neural activity and heat transfer by blood flow. However, the effect of neuronal activity on the rBT especially remains unclear. To elucidate the relationship between rBT and neuronal activities, we simultaneously recorded brain temperature and electrophysiological neuronal activities of rats, in response to somatosensory stimuli (electrical stimuli, L-menthol and capsaicin) to the tongue. The rBT was monitored with a fine thermocouple inserted into the primary gustatory cortical area. The rBT rose by 0.01–0.08 ◦ C after the neuronal activation. The effect was stronger with L-menthol and capsaicin than that with electrical stimuli. Our results indicate that the stimulus-induced neuronal activation increases the regional brain temperature depending on the nature of stimuli. doi:10.1016/j.neures.2009.09.661

P1-p20 Phenotypic analysis of a new fish mutant harboring RohonBeard neuron defects Hiromi Hirata, Yuri Nakano, Yoichi Oda Nagoya University, Japan Small fish are amenable vertebrate models to study motor development and disorder. A new zebrafish mutant, which was isolated by an ENU mutagenesis, does not respond to tactile stimulation at 2 day of development. In teleosts and amphibians, Rohon-Beard (RB) neurons, a subset of HuC-positive neurons in dorsal spinal cord, initially function as primary sensory neurons at early developmental stage, but eventually disappear up to 4 day by programmed cell death and replaced by dorsal root ganglion neurons. This RB cell death is induced in an electrical activity-dependent manner. In vivo whole-cell recordings revealed that RB neurons in the mutant did not exhibit normal firings in response to somatic depolarization, associated with reduction of TTX-sensitive inward current. Many mutant RB cells survived after 4 day without undergoing apoptosis. These results suggest that impairment of touchelicited behavior of the mutants is caused by defects in the voltage-gated sodium channel in the RB neurons, resulting in a reduction of RB cell death. doi:10.1016/j.neures.2009.09.662

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simultaneously, HN antagonized A␤-mediated inhibition of K+ currents. Our results indicated that HN suppresses A␤-induced inhibition of Ca2+ -indepent K+ currents in neurons. doi:10.1016/j.neures.2009.09.664

P2-a03 Effects of coaction of dopaminergic modulation and inward rectifying potassium current inactivation on the biophysical properties of medium spiny neurons John E. Steephen, Rohit Manchanda Indian Institute of Technology Bombay, India Inward rectifying potassium (KIR) currents inactivate significantly in ∼40% of the medium spiny (MS) neurons of nucleus accumbens (NAc) but not in the rest, which may lead to differences in input processing by these two groups. Dopaminergic modulation is known to regulate reward-related behaviors associated with NAc. No studies have yet been reported on the effects of the modulation on biophysical properties of MS neurons in conjunction with KIR current inactivation. Using a model of the MS neuron, we investigate the influence of this combined effect using injected current inputs. Our study shows that in conjunction with KIR current inactivation, while D2-receptor-modulation facilitates depolarization, spike frequency and spike onset, D1-receptor-modulation enhances cell gain causing spike frequency dependent excitability changes. The higher prevalence of KIR inactivation in the core region as compared to the shell in NAc suggests a possible role for the phenomenon along with dopamine in core mediated dopamine dependent learning. doi:10.1016/j.neures.2009.09.665

P2-a04 Antidepressant drug Amoxapine inhibited the delayed rectifier outward K+ current in the mouse cortical neurons Yan-Lin He, Xiao-Wei Fei, Yan-Ai Mei School of Life Sciences, Institutes of Brain Science and State Key Laboratory of Medical Neurobiology, Fudan University, Shanghai, China Ion channels as the target of drug was modulated directly by antidepressant drug, but whether the modulation involved in the intracellular signal pathway is poor recognized. In this study, we demonstrated that antidepressant drug Amoxapine suppressed the rectifier outward K+ current IK in the mouse cortical neuron. At a concentration of 0.1 nM to 5 ␮M, Amoxapine reversibly inhibited IK in a dosedependent manner with the modulation of steady-state activation and inactivation properties. The application of forskolin or 8-Br-cAMP mimicked the inhibitory effect of amoxapine on IK , and abolished the Amoxapine-induced effect on IK . H-89, an inhibitor of PKA, augmented IA amplitude and completely eliminated the amoxapineinduced inhibitory effect on IK . A cAMP assay revealed that amoxapine significantly increased intracellular cAMP level. Our study first indicated that amoxapine inhibits the IK current in neurons by cAMP/PKA-dependent pathways. doi:10.1016/j.neures.2009.09.666

P2-a05 Compartmentalized distribution of ␣1G subunit of T-type calcium channel in the dorsal lateral geniculate nucleus of mouse brain Laxmi Parajuli 1,2 , Yugo Fukazawa 1,2 , Masahiko Watanabe 3 , Ryuichi Shigemoto 1,2 1

P2-a02 Humanin suppresses A␤-mediated inhibition of Ca2+ indepent K+ currents in hippocampal neurons Pengjun Zhang, Yu Zhang, Xiaorong Yang, Aijuan Tan, Huixia Jiang, Ce Zhang Department of Neurobiology, Shanxi Medical University, Taiyuan, China Several evidence indicate that an abnormal accumulation of ␤-amyloid peptide (A␤) is the leading cause and pathological characteristics of Alzheimer, s disease (AD). K+ channel is one of the critical mechanisms involved in A␤-induced neurotoxicity. Humanin (HN) were recently reported that exhibited marked neuroprotection against AD-related insults. However,no evidence showed the electrophysiological effects of HN on neurons. Here, we investigated the effects of HN on A␤25-35 mediated inhibition of the Ca2+ -indepent K+ currents (including IA and IK ) by whole cell patch clamp.The results showed that: (1)the amplitude of Ca2+ -indepent K+ currents (IA and IK ) were significantly decreased after application of A␤; (2) pretreatment of HN prevented A␤-mediated inhibition of K+ currents; (3) post administion of HN reversed A␤-mediated inhibition of K+ currents; 4) in the presence of A␤and HN

National Institute for Physiological Sciences Myodaiji, Okazaki, Japan; 2 The Graduate University for Advanced Studies, SOKENDAI, Japan; 3 Department of Anatomy, Hokkaido University, Sapporo, Japan Neural communication in the dorsal lateral geniculate nucleus (dLGN) largely depends on the precise subcellular distribution of ion channels, in which the Ttype calcium channels plays a crucial role. The purpose of this study was to analyze the distinct subcellular localization of ␣ 1G subunit of T-type Ca2+ channel by means of a highly specific antibody against this subunit. At the light microscopic level, the thalamic region exhibited an intense immunoreactivity. Electron microscopic analysis of immunogold demonstrated that this channel is selectively distributed in the somato-dendritic surface of the dLGN cells. The density of immunoparticles was negatively correlated with the dendritic cross sectional length. This polarized and compartmentalized localization of T-type calcium channels in dLGN suggests their involvement in regulating dendritic calcium dependent processes. doi:10.1016/j.neures.2009.09.667