Roles of Calcium/Calmodulin-Dependent Kinase II in Long-Term Memory Formation in Crickets

Ca2+/calmodulin (CaM)-dependent protein kinase II (CaMKII) is a key molecule in many systems of learning and memory in vertebrates, but roles of CaMKII in invertebrates have not been characterized in detail. We have suggested that serial activation of NO/cGMP signaling, cyclic nucleotide-gated channel, Ca2+/CaM and cAMP signaling participates in long-term memory (LTM) formation in olfactory conditioning in crickets, and here we show participation of CaMKII in LTM formation and propose its site of action in the biochemical cascades. Crickets subjected to 3-trial conditioning to associate an odor with reward exhibited memory that lasts for a few days, which is characterized as protein synthesis-dependent LTM. In contrast, animals subjected to 1-trial conditioning exhibited memory that lasts for only several hours (mid-term memory, MTM). Injection of a CaMKII inhibitor prior to 3-trial conditioning impaired 1-day memory retention but not 1-hour memory retention, suggesting that CaMKII participates in LTM formation but not in MTM formation. Animals injected with a cGMP analogue, calcium ionophore or cAMP analogue prior to 1-trial conditioning exhibited 1-day retention, and co-injection of a CaMKII inhibitor impaired induction of LTM by the cGMP analogue or that by the calcium ionophore but not that by the cAMP analogue, suggesting that CaMKII is downstream of cGMP production and Ca2+ influx and upstream of cAMP production in biochemical cascades for LTM formation. Animals injected with an adenylyl cyclase (AC) activator prior to 1-trial conditioning exhibited 1-day retention. Interestingly, a CaMKII inhibitor impaired LTM induction by the AC activator, although AC is expected to be a downstream target of CaMKII. The results suggest that CaMKII interacts with AC to facilitate cAMP production for LTM formation. We propose that CaMKII serves as a key molecule for interplay between Ca2+ signaling and cAMP signaling for LTM formation, a new role of CaMKII in learning and memory

Heterogeneous distribution of doublecortin-expressing cells surrounding the rostral migratory stream in the juvenile mouse

In the postnatal mammalian brain, neural stem cells of the ventricular-subventricular zone continue to generate doublecortin (Dcx)-expressing immature neurons. Throughout life, these immature neurons migrate to the olfactory bulb through the rostral migratory stream (RMS). In this study, we investigated the distribution of these putative immature neurons using enhanced green fluorescent protein (EGFP) expression in the area surrounding the RMS of the juvenile Dcx-EGFP mice. Through the combined use of an optical clearing reagent (a 2,2 '-thiodiethanol solution) and two-photon microscopy, we visualized three-dimensionally the EGFP-positive cells in the entire RMS and its surroundings. The resulting wide-field and high-definition images along with computational image processing methods developed in this study were used to comprehensively determine the position of the EGFP-positive cells. Our findings revealed that the EGFP-positive cells were heterogeneously distributed in the area surrounding the RMS. In addition, the orientation patterns of the leading process of these cells, which displayed the morphology of migrating immature neurons, differed depending on their location. These novel results provide highly precise morphological information for immature neurons and suggest that a portion of immature neurons may be detached from the RMS and migrate in various directions

On the Role of Ascorbic Acid in the Synthesis of Single-Crystal Hyperbranched Platinum Nanostructures

In this paper, a very simple and efficient wet chemical route is proposed to directly produce single-crystal hyperbranched platinum nanostructures (HPNSs), in high yield, within 10 min simply by sonication treatment of an aqueous solution containing K2PtCl4 and ascorbic acid (AA) only. The results in this report demonstrate that even in the absence of any purposely added structure-directing agent and seed mediator, reaction kinetics of AA and the released byproduct derived from AA oxidation, that is, 2,3-diketo-1-gulonic acid (DGA), are capable of producing single-crystal HPNSs in aqueous medium. In addition to being a commonplace reducing agent (electron donor), AA plays a more important role relied on its byproduct, DGA, which serves as a shape-directing agent to direct the branched growth. The new insight into the role of AA in the synthesis of single-crystal HPNSs reported here provides a new viewpoint for further understanding the formation mechanism of anisotropic platinum nanostructures

The importance of family caregiving to achieving palliative care at home

Rationale: The primary setting of palliative care has shifted from inpatient care to patients’ residences. Family caregiving is essential for patients with life-limiting illnesses to receive palliative care at home, however little information is available regarding potential interventions to achieve palliative homecare for those without sufficient support from family members in various settings, including disasters. Patient concerns: In March 2011, Fukushima, Japan experienced an earthquake, tsunami and nuclear disaster. In August 2015, a 59-year-old Japanese female presented to our hospital, located 23 km north of Fukushima Daiichi Nuclear Power Plant, with a right breast ulcer. Diagnoses: The patient was diagnosed with stage IV breast cancer. Interventions: The patient's general condition gradually worsened despite a one-year course of chemotherapy, and she became bedridden after a fall in October 2016. Although the patient wished to receive palliative homecare, this appeared challenging to achieve because she resided alone in a temporary housing shelter. Although she originally lived with her family in Odaka District, Fukushima, she relocated outside of the city following evacuation orders after the disaster. The evacuation orders for Odaka District were still in effect when she returned to the city alone in 2014. We contacted her sister who moved apart from her during the evacuation, and explained the necessity of family caregiving to enable her palliative homecare. Outcomes: The sister decided to move back to their original residence in Odaka District and live with the patient again. The patient successfully spent her end-of-life period and died at home.Lessons: Health care providers and community health workers may need to take a pro-active approach to communicating with family members to draw informal support to enable patients’ end-of-life management according to their values and preferences. This is a lesson which may be applicable to broader healthcare settings beyond cancer, or disaster contexts, considering that population ageing and social isolation may continue to advance worldwide

No effects of CaMKII inhibitors on 1-hour retention.

<p>Three groups of animals were each injected with 3 µl of saline containing 1% DMSO (designated as saline (D)) or saline containing 2 mM KN-62 or 2 mM KN-93 (dissolved in 1% DMSO) 20 min prior to 3-trial conditioning. Relative preference between the rewarded odor and control odor was tested before and at 1 hour after training. PIs for the rewarded odor before (white bars) and after (grey bars) training are shown as box and whisker diagrams. Odor preferences before and after training are compared by WCX test. Odor preferences after training of different groups were compared by the M-W test. The results of statistical comparisons are shown by asterisks (*** P<0.001, NS P>0.05, adjusted by Holm's method).</p