Behavioral impairment in SHATI/NAT8L knockout mice via dysfunction of myelination development

We have identified SHATI/NAT8L in the brain of mice treated with methamphetamine. Recently, it has been reported that SHATI is N-acetyltransferase 8-like protein (NAT8L) that produces N-acetylaspatate (NAA) from aspartate and acetyl-CoA. We have generated SHATI/NAT8L knockout (Shati−/−) mouse which demonstrates behavioral deficits that are not rescued by single NAA supplementation, although the reason for which is still not clarified. It is possible that the developmental impairment results from deletion of SHATI/NAT8L in the mouse brain, because NAA is involved in myelination through lipid synthesis in oligodendrocytes. However, it remains unclear whether SHATI/NAT8L is involved in brain development. In this study, we found that the expression of Shati/Nat8l mRNA was increased with brain development in mice, while there was a reduction in the myelin basic protein (MBP) level in the prefrontal cortex of juvenile, but not adult, Shati−/− mice. Next, we found that deletion of SHATI/NAT8L induces several behavioral deficits in mice, and that glyceryltriacetate (GTA) treatment ameliorates the behavioral impairments and normalizes the reduced protein level of MBP in juvenile Shati−/− mice. These findings suggest that SHATI/NAT8L is involved in myelination in the juvenile mouse brain via supplementation of acetate derived from NAA. Thus, reduction of SHATI/NAT8L induces developmental neuronal dysfunction

Effects of midazolam on acquisition and extinction of conditioned taste aversion memory in rats.

Some intravenous anesthetic agents such as midazolam are known to induce anterograde and retrograde amnesia. We analyzed the effect of midazolam by the conditioned taste aversion (CTA) acquisition and retention. After the rats were offered 0.1% sodium saccharin (Sac) as conditioned stimulus (CS), an intraperitoneal (i.p.) injection of several concentrations (5-30mg/kg) of midazolam was followed by an i.p. injection of 0.15M LiCl (2% of body weight) as unconditioned stimulus (US). The rats, which acquired CTA by every CS-US paradigm, strongly avoided Sac on the 1st test day after conditioning and maintained the avoidance for 3 days. We have already reported that Sac intake abruptly increased on the 2nd test day and the almost complete extinction occurred on the 3rd test day after conditioning by injection of subhypnotic dose of propofol before LiCl-injection. In contrast, we found that subhypnotic dose of midazolam suppressed not only CTA acquisition, but also CTA retention. On the other hand, an alpha2-adrenergic blocker, yohimbin (1mg/kg) suppressed only the CTA retention. These results suggest that the subhypnotic doses of midazolam firstly affect the acquisition mechanism of the CTA memory (CTAM), resulting the suppression of the retention of CTAM

Reconstituted Ion Channels of Frog Fungiform Papilla Cell Membrane.

We identified a Cl^- channel, two K^+ channels and a cAMP-gated channel which were isolated from bullfrog fungiform papilla cell membranes and incorporated into phospholipid bilayers using the tip-dip method. The 156 pS channels were inhibited by 100μM 4, 4\u27-diisothiocyanostilbene-2, 2\u27-disulfonic acid (DIDS) and displayed the reversal potential identical to the equilibrium potential of Cl^-, it was identified as a Cl^- channel. Two types of K^+ channel had unitary conductances of 79 and 43 pS, which may correspond to those of Ca^-activated and cAMP-blockable K^+ channels observed in isolated intact frog taste cell membranes, respectively. These results suggest that the tip-dip method is useful for stable investigation of the properties of ion channels already identified in the taste cell. Furthermore, the 23 pS channels were newly found and were activated directly by internal cAMP as cyclic nucleotide-gated (CNG) nonselective cation channels established in olfactory receptor cells. Thus, our results suggest the possibility that besides Cl^- and K^+ channels, the cAMP-gated channels contribute to taste transduction

Memory-specific correlated neuronal activity in higher-order auditory regions of a parrot.

Funder: Kayamori Foundation for Informational Science AdvancementFunder: the Netherlands Organization for Scientific ResearchFunder: Multi-Career Path Support Model for Female Researchers project of Japan’s Women UniversityFunder: Japan Society for the Promotion of Science (JSPS) Grant-in-AidFunder: ALW Open Competition and GW Horizon ProgrammeMale budgerigars (Melopsittacus undulatus) are open-ended learners that can learn to produce new vocalisations as adults. We investigated neuronal activation in male budgerigars using the expression of the protein products of the immediate early genes zenk and c-fos in response to exposure to conspecific contact calls (CCs: that of the mate or an unfamiliar female) in three subregions (CMM, dNCM and vNCM) of the caudomedial pallium, a higher order auditory region. Significant positive correlations of Zenk expression were found between these subregions after exposure to mate CCs. In contrast, exposure to CCs of unfamiliar females produced no such correlations. These results suggest the presence of a CC-specific association among the subregions involved in auditory memory. The caudomedial pallium of the male budgerigar may have functional subdivisions that cooperate in the neuronal representation of auditory memory