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Biomedical subjects

Shin Nagayama

Publications and source records attributed to Shin Nagayama.

6 recordsLinked to original sources
PubMed2006

Altered cerebellar function in mice lacking CaV2.3 Ca2+ channel.

Voltage-dependent Ca(2+) channels play important roles in cerebellar functions including motor coordination and learning. Since abundant expression of Ca(V)2.3 Ca(2+) channel gene in the cerebellum was detected, we searched for possible deficits in the cerebellar functions in the Ca(V)2.3 mutant mice. Behavioral analysis detected in delayed motor learning in rotarod tests in mice heterozygous and homozygous for the Ca(V)2.3 gene disruption (Ca(V)2.3+/- and Ca(V)2.3-/-, respectively). Electrophysiological analysis of mutant mice revealed perplexing results: deficit in long-term depression (LTD) at the parallel fiber Purkinje cell synapse in Ca(V)2.3+/- mice but apparently normal LTD in Ca(V)2.3-/- mice. On the other hand, the number of spikes evoked by current injection in Purkinje cells under the current-clamp mode decreased in Ca(V)2.3 mutant mice in a gene dosage-dependent manner, suggesting that Ca(V)2.3 channel contributed to spike generation in Purkinje cells. Thus, Ca(V)2.3 channel seems to play some roles in cerebellar functions.

Action Potentials↗
PubMed2004

Detection and masking of spoiled food smells by odor maps in the olfactory bulb.

Two major causes of spoiled food smells such as fatty, fishy off-flavors are alkylamines liberated by bacterial actions and aliphatic acids-aldehydes generated by lipid oxidation. Using the method of intrinsic signal imaging, we mapped alkylamine-responsive glomeruli to a subregion of the aliphatic acid-responsive and aldehyde-responsive cluster in the odor maps of rat olfactory bulb. Extracellular single-unit recordings from mitral-tufted cells in the subregion showed that individual cells responded to the alkylamines in addition to acids and aldehydes. Responses of mitral-tufted cells tended to last for a long period (5-88 sec) even after the cessation of the alkylamine stimulation. These results suggest that the subregion is part of the representation of the fatty, fishy odor quality. Fennel and clove, spices known to add flavor and mask the fatty, fishy odor, activated glomeruli in the surrounding clusters and suppressed the alkylamine-induced and acid-aldehyde-induced responses of mitral cells, suggesting that the odor masking is mediated, in part, by lateral inhibitory connections in the odor maps of the olfactory bulb.

Amines↗
PubMed2004

Mitral and tufted cells differ in the decoding manner of odor maps in the rat olfactory bulb.

Mitral and tufted cells in the mammalian olfactory bulb are principal neurons, each type having distinct projection pattern of their dendrites and axons. The morphological difference suggests that mitral and tufted cells are functionally distinct and may process different aspects of olfactory information. To examine this possibility, we recorded odorant-evoked spike responses from mitral and middle tufted cells in the aliphatic acid- and aldehyde-responsive cluster at the dorsomedial part of the rat olfactory bulb. Homologous series of aliphatic acids and aldehydes were used for odorant stimulation. In response to adequate odorants, mitral cells showed spike responses with relatively low firing rates, whereas middle tufted cells responded with higher firing rates. Examination of the molecular receptive range (MRR) indicated that most mitral cells exhibited a robust inhibitory MRR, whereas a majority of middle tufted cells showed no or only a weak inhibitory MRR. In addition, structurally different odorants that activated neighboring clusters inhibited the spike activity of mitral cells, whereas they caused no or only a weak inhibition in the middle tufted cells. Furthermore, responses of mitral cells to an adequate excitatory odorant were greatly inhibited by mixing the odorant with other odorants that activated neighboring glomeruli. In contrast, odorants that activated neighboring glomeruli did not significantly inhibit the responses of middle tufted cells to the adequate excitatory odorant. These results indicate a clear difference between mitral and middle tufted cells in the manner of decoding the glomerular odor maps.

Action Potentials↗
PubMed2002

Molecular-feature domains with posterodorsal-anteroventral polarity in the symmetrical sensory maps of the mouse olfactory bulb: mapping of odourant-induced Zif268 expression.

Individual glomeruli in the mammalian olfactory bulb presumably represent a single type of odourant receptor. Thus, the glomerular sheet provides odourant receptor maps at the surface of the olfactory bulb. To understand the basic spatial organization of the olfactory sensory maps, we first compared the spatial distribution of odourant-induced responses measured by the optical imaging of intrinsic signals with that detected immunohistochemically by expressions of Zif268, one of the immediate early gene products in juxtaglomerular cells. In the dorsal surface of the bulb, we detected a clear correlation in the spatial pattern between these responses. In addition, the molecular-feature domains and their polarities (spatial shifts of responses with an increase in carbon chain length) that were defined by the optical imaging method could be also detected by the Zif268 mapping method. We then mapped the Zif268 signals over the entire olfactory bulb using a homologous series of fatty acids and aliphatic alcohols as stimulus odourants. We superimposed the Zif268 signals onto the standard unrolled map with the help of cell adhesion molecule compartments. Each odourant typically elicited two pairs of clusters of dense Zif268 signals. The results showed that molecular-feature domains and their polarities were arranged symmetrically at stereotypical positions in a mirror-image fashion between the lateral and the medial sensory maps. The polarity of each domain was roughly in parallel with the posterodorsal-anteroventral axis that was defined by the cell adhesion molecule compartments. These results suggest that the molecular-feature domain with its fixed polarity is one of the basic structural units in the spatial organization of the odourant receptor maps in the olfactory bulb.

Animals↗
PubMed2001

Novel Cav2.1 splice variants isolated from Purkinje cells do not generate P-type Ca2+ current.

The alpha(1)2.1 (alpha(1A)) subunits of P-type and Q-type Ca(2+) channels are encoded by a single gene, Cacna1a. Although these channels differ in the inactivation kinetics and sensitivity to omega-agatoxin IVA, the mechanism underlying these differences remains to be clarified. Alternative splicings of the Cacna1a transcript have been postulated to contribute to the respective properties, however, the splice variants responsible for P-type Ca(2+) channels have not been identified. To explore P-type-specific splice variants, we aimed at cloning alpha(1)2.1 from isolated mouse Purkinje cells using single-cell reverse transcription-PCR, because in Purkinje cells P-type currents dominate over the whole currents (>95%) with Q-type currents undetected. As a result, two novel splice variants were cloned. Compared with the previously cloned mouse alpha(1)2.1, two novel variants had additional 48 amino acids at the amino termini, six single amino acid changes, and splicing variations at the exon 46/47 boundary, which produced different carboxyl termini. Furthermore, one variant had one RNA editing site. However, electrophysiological and pharmacological studies indicated that these variants did not generate P-type current in cultured cells. These results suggest that P-type-specific splice variants may exist but that post-translational processing or modification by uncharacterized interacting proteins is also required for generating the P-type current.

Alternative Splicing↗