Computational studies of activity propagations through feed-forward networks of burst neurons

s / Neuroscience Research 58S (2007) S1–S244 S41 O1P-E1Ø Importinand expression in the neonatal and adult mouse brain Koji Hosokawa, Mayumi Nishi, Mitsuhiro Kawata Department of Anatomy and Neurobiology, Kyoto Prefectural University of Medicine, Kyoto, Japan Importinand mediate nucleocytoplasmic translocation of macromolecules across the nuclear pore complex. While the functional differences of importins in the neural cells remain unclear, the expression features should be quite an important issue to elucidate these functions. Recent reports showed importinand except for importin2 were expressed in the brain, although the detail expression profile of each gene has not yet been investigated. We performed in situ hybridization to clarify the distributions of mouse importins and in the central nervous system of neonatal and adult mice. Importins mRNAs were expressed throughout the brain and spinal cord, whereas imporitn2 mRNA was expressed only in olfactory bulbs, locus ceruleus and cranial nerve nuclei. In addition, importin2 and mRNAs were expressed in the external granule layer of neonatal cerebellar cortex. Ubiquitous expression of importins suggests their housekeeping properties, while discrete expression of importin2 implies a particular function in the central nervous system. O1P-E11 The functional analysis of TRPM1 in retinal bipolar cells Chieko Koike1, Rikako Sanuki1, Kentaro Miyata2, Toshiyuki Koyasu2, Tomomitsu Miyoshi3, Hajime Sawai3, Mineo Kondo2, Jiro Usukura4, Takahisa Furukawa1 1 Department of Developmental Biology, Osaka Bioscience Institute, Japan; 2 Department of Ophthalmology, Nagoya University Graduate School of Medicine, Japan; 3 Department of Physiology, Graduate School of Medicine, Osaka University, Japan; 4 Department of Materials Physics and Engineering, Graduate School of Engineering, Nagoya University, Japan Retinal bipolar cells convey neural signals from photoreceptors to amacrine and ganglion cells. TRPM1, one of the transient receptor potential (TRP) family members, was identified as a prognostic marker for metastasis of localized melanoma. However, its channel activity and biological function have been poorly understood. We cloned a TRPM1 long form containing an ion transporter domain, and we detected TRPM1 expression specifically in retinal bipolar cells. Interestingly, TRPM1 KO mice lacked electrophysiological activities under both photopic and scotopic conditions, although they retained intact photoreceptor activities under the same conditions. Our data indicate a pivotal role of TRPM1 in electrophysiological function of retinal bipolar cells. Research funds: 18390092, 18022044, 18590090 O1P-E12 Lateral mobility of voltage sensor domain of bacterial sodium channels Hitoshi Nagura1, Katsumasa Irie2, Tomoya Imai1, Takushi Shimomura1, Toshihide Hige1, Yoshinori Fujiyoshi1 1 Department Biophysics, Graduate School of Science, Kyoto University, Kyoto, Japan; 2 RIKEN SPring-8 Center, Harima Institute, Hyogo, Japan Proximity between voltage sensor and pore domains of bacterial Na channels (NaChBac) was examined by introducing paired cysteines on various residues in extracellular part of S4 and S5 segments. E. coli expression test showed that T110C/M164C mutant most efficiently makes intersubunit disulfide bonds. When expressed in HEK cells, the mutant was electrophysiologically inactive but resumed normal activity upon bath application of DTT. Single mutation of M164C (S5) showed neither a disulfide bond nor current reduction. To our surprise, unlike those of double mutants, the current recordings however showed that T110C (S4) single mutant was likely to make disulfide bonds together in the channel tetramer. These results were also confirmed by another strategy using Zn2+ chelation between histidine residues introduced at the same site as above. Our results suggest that the voltage sensor domains of NaChBac should be much more mobile laterally than that has been suggested in other voltage-gated ion channels. O1P-E13 Synchronization of excitatory neurons with strongly heterogeneous phase response Yasuhiro Tsubo1,2, Jun-nosuke Teramae1, Tomoki Fukai1 1 RIKEN BSI, Wako, Saitama, Japan; 2 Tokyo Metropolitan Institute for Neuroscience, Fuchu, Tokyo, Japan Synchronous firing of cortical neurons is considered to play an active role in cognitive functions of the brain. Synchronizing dynamics depends not only on the neuronal network structures but on the cellular intrinsic properties. Phase response curve (PRC) is an intrinsic property of neurons, and it describes how a timing shift in the next output spike depends on the timing of the input stimulus and has crucial information about synchronization. Our in vitro study demonstrated that the PRC shapes of cortical neurons are heterogeneous. Little is known about the dynamics of the neurons with heterogeneous PRC. We investigated the dynamics of such populations through the globally coupling with the excitatory synaptic interaction. We found that in hard-to-synchronizing neurons, small heterogeneity of PRC can destroy the frequency synchronization, while in the easy-to-synchronization neurons, heterogeneity drives the perfectly synchronizing state into the partially synchronizing state. Research funds: KAKENHI (17022036), Grant-in-Aid for Young Scientists (B) 50384722 O1P-E14 Nefiracetam potentiates NMDA receptor function via protein kinase C activation Shigeki Moriguchi1, Norifumi Shioda1, Toshio Narahashi2, Kohji Fukunaga1 1 Department of Pharmacology, Tohoku University, Sendai, Japan; 2 Deapartment of Molecular Pharmacology and Biological Chemistry, Northwestern University, Chicago, USA Nicotinic acetylcholine receptors and NMDA receptors are known to be down-regulated in the brain of Alzheimer’s disease patients. We have previously demonstrated that the nootropic drug nefiracetam potentiates the activity of both nicotinic acetylcholine and NMDA receptors and that nefiracetam modulates the glycine binding site of the NMDA receptor. We studied their roles in nefiracetam action on the NMDA receptor by the whole-cell patch-clamp technique and immunoblotting analysis using rat cortical or hippocampal neurons in primary culture. The nefiracetam potentiation of NMDA currents was inhibited by the PKC inhibitor chelerythrine, but not by the PKA inhibitor H-89. In immunoblotting analysis, nefiracetam treatment increased the PKCalpha activity with a bell-shaped dose–response relationship peaking at 10 nM, thereby increasing phosphorylation of PKC substrate and NMDA receptor. Such an increase in PKCalpha-mediated phosphorylation was prevented by chelerythine. O1P-E15 Computational studies of activity propagations through feed-forward networks of burst neurons Jun-nosuke Teramae1, Hideyuki Cateau1, Alex Reyes2, Tomoki Fukai1 1 BSI, RIKEN, Saitama, Japan; 2 Center for Neuroscience, New York University, USA Feed-forward networks of neurons, synfire-chains, are a well-studied circuit to propagate spikes. Recent experiments showed neurons in the high vocal centre of songbirds exhibited sequences of bursts while the bird was singing. The result indicates the neural circuit of the bird has a feed-forward network that propagates spike bursts. While the propagation of singlet spikes has been studied, that of bursts remains unknown. Here, we studied the propagation of bursts in a feed-forward network of intrinsic bursting neurons and found that the burst propagation has novel properties that was not present in the single-spike propagation: (i) bursts propagate with a speed that depends on the bursting mode, i.e., the number of spikes in each burst (ii) temporal structures of spikes within a burst show complex evolution during propagation. Our results indicate a possibility that intrinsic properties of cells may play an active role to increase computational abilities of sequence generation in the brain. Research funds: Grant-in-Aid for Young Scientists (B) 50384722 and KAKENHI 17022036