Calcium-dependent activator protein for secretion 2 is involved in dopamine release in mouse midbrain neurons.

The Ca-dependent activator protein for secretion (CAPS/CADPS) family protein facilitates catecholamine release through the dense-core vesicle exocytosis in model neuroendocrine cell lines. However, it remains unclear if it induces dopamine release in the central neurons. This study aimed to examine the expression and function of CADPS2, one of the two CADPS paralogs, in dopamine neurons of the mouse midbrain.

Oxytocinergic projection from the hypothalamus to supramammillary nucleus drives recognition memory in mice.

Oxytocin (OXT) neurons project to various brain regions and its receptor expression is widely distributed. Although it has been reported that OXT administration affects cognitive function, it is unclear how endogenous OXT plays roles in cognitive function. The present study examined the role of endogenous OXT in mice cognitive function.

Disulfiram Produces Potent Anxiolytic-Like Effects Without Benzodiazepine Anxiolytics-Related Adverse Effects in Mice.

Disulfiram is an FDA approved drug for the treatment of alcoholism. The drug acts by inhibiting aldehyde dehydrogenase, an enzyme essential to alcohol metabolism. However, a recent study has demonstrated that disulfiram also potently inhibits the cytoplasmic protein FROUNT, a common regulator of chemokine receptor CCR2 and CCR5 signaling.

Improved clearing method contributes to deep imaging of plant organs.

Tissue clearing methods are increasingly essential for the microscopic observation of internal tissues of thick biological organs. We previously developed TOMEI, a clearing method for plant tissues; however, it could not entirely remove chlorophylls nor reduce the fluorescent signal of fluorescent proteins. Here, we developed an improved TOMEI method (iTOMEI) to overcome these limitations.

Suppression of amyloid-β secretion from neurons by cis-9, trans-11-octadecadienoic acid, an isomer of conjugated linoleic acid.

Two common conjugated linoleic acids (LAs), cis-9, trans-11 CLA (c9,t11 CLA) and trans-10, cis-12 CLA (t10,c12 CLA), exert various biological activities. However, the effect of CLA on the generation of neurotoxic amyloid-β (Aβ) protein remains unclear. We found that c9,t11 CLA significantly suppressed the generation of Aβ in mouse neurons.

Task-Related c-Fos Expression in the Posterior Parietal Cortex During the "Rubber Tail Task" Is Diminished in Ca-Dependent Activator Protein for Secretion 2 ()-Knockout Mice.

Rubber hand illusion (RHI), a kind of body ownership illusion, is sometimes atypical in individuals with autism spectrum disorder; however, the brain regions associated with the illusion are still unclear. We previously reported that mice responded as if their own tails were being touched when rubber tails were grasped following synchronous stroking to rubber tails and their tails (a "rubber tail illusion", RTI), which is a task based on the human RHI; furthermore, we reported that the RTI response was diminished in knockout (-KO) mice that exhibit autistic-like phenotypes. Importance of the posterior parietal cortex in the formation of illusory perception has previously been reported in human imaging studies.

Dietary cis-9, trans-11-conjugated linoleic acid reduces amyloid β-protein accumulation and upregulates anti-inflammatory cytokines in an Alzheimer's disease mouse model.

Conjugated linoleic acid (CLA) is an isomer of linoleic acid (LA). The predominant dietary CLA is cis-9, trans-11-CLA (c-9, t-11-CLA), which constitutes up to ~ 90% of total CLA and is thought to be responsible for the positive health benefits associated with CLA. However, the effects of c-9, t-11-CLA on Alzheimer's disease (AD) remain to be elucidated.

CAPS1 is involved in hippocampal synaptic plasticity and hippocampus-associated learning.

Calcium-dependent activator protein for secretion 1 (CAPS1) is a key molecule in vesicular exocytosis, probably in the priming step. However, CAPS1's role in synaptic plasticity and brain function is elusive. Herein, we showed that synaptic plasticity and learning behavior were impaired in forebrain and/or hippocampus-specific Caps1 conditional knockout (cKO) mice by means of molecular, physiological, and behavioral analyses.

CAPS2 Deficiency Impairs the Release of the Social Peptide Oxytocin, as Well as Oxytocin-Associated Social Behavior.

Ca-dependent activator protein for secretion 2 (CAPS2) regulates dense-core vesicle (DCV) exocytosis to facilitate peptidergic and catecholaminergic transmitter release. CAPS2 deficiency in mice has mild neuronal effects but markedly impairs social behavior. Rare alterations also occur in autism spectrum disorder, although whether CAPS2-mediated release influences social behavior remains unclear.

The Ser19Stop single nucleotide polymorphism (SNP) of human PHYHIPL affects the cerebellum in mice.

The HapMap Project is a major international research effort to construct a resource to facilitate the discovery of relationships between human genetic variations and health and disease. The Ser19Stop single nucleotide polymorphism (SNP) of human phytanoyl-CoA hydroxylase-interacting protein-like (PHYHIPL) gene was detected in HapMap project and registered in the dbSNP. PHYHIPL gene expression is altered in global ischemia and glioblastoma multiforme.

Comprehensive Profiling of Gene Expression in the Cerebral Cortex and Striatum of BTBRTF/ArtRbrc Mice Compared to C57BL/6J Mice.

Mouse line BTBR + /J (hereafter referred as to BTBR/J) is a mouse strain that shows lower sociability compared to the C57BL/6J mouse strain (B6) and thus is often utilized as a model for autism spectrum disorder (ASD). In this study, we utilized another subline, BTBRTF/ArtRbrc (hereafter referred as to BTBR/R), and analyzed the associated brain transcriptome compared to B6 mice using microarray analysis, quantitative RT-PCR analysis, various bioinformatics analyses, and hybridization. We focused on the cerebral cortex and the striatum, both of which are thought to be brain circuits associated with ASD symptoms.

Journey of brain-derived neurotrophic factor: from intracellular trafficking to secretion.

Brain-derived neurotrophic factor (BDNF) is known to control a wide variety of brain functions, ranging from memory formation to food intake. However, since the BDNF levels are extremely low in the nervous system, the dynamics in neurons from intracellular trafficking to secretion is absolutely complicated; the understanding is not fully promoted. We here review the findings of those critical mechanisms from intracellular trafficking to the secretion of BDNF.

CAPS2 deficiency induces proopiomelanocortin accumulation in pituitary and affects food intake behavior in mice.

Proopiomelanocortin (POMC) is a neuropeptide precursor produced in the anterior and intermediate pituitary lobes, the hypothalamic arcuate nucleus (ARC), and solitary tract nucleus. Alpha-melanocyte-stimulating hormone (α-MSH) is a cell type specific POMC derivative that is essential for regulating feeding, and energy homeostasis. However, the molecular mechanism underlying POMC/α-MSH secretion remains unclear.

Cortico-amygdala interaction determines the insular cortical neurons involved in taste memory retrieval.

The insular cortex (IC) is the primary gustatory cortex, and it is a critical structure for encoding and retrieving the conditioned taste aversion (CTA) memory. In the CTA, consumption of an appetitive tastant is associated with aversive experience such as visceral malaise, which results in avoidance of consuming a learned tastant. Previously, we showed that levels of the cyclic-AMP-response-element-binding protein (CREB) determine the insular cortical neurons that proceed to encode a conditioned taste memory.

Excitation of prefrontal cortical neurons during conditioning enhances fear memory formation.

Animals can remember a situation associated with an aversive event. Contextual fear memory is initially encoded and consolidated in the hippocampus and gradually consolidated in multiple brain regions over time, including the medial prefrontal cortex (PFC). However, it is not fully understood how PFC neurons contribute to contextual fear memory formation during learning.

Comparative gene expression analysis of the engulfment and cell motility (ELMO) protein family in the mouse brain.

Engulfment and cell motility (ELMO) proteins bind to Dock180, a guanine nucleotide exchange factor (GEF) of the Rac family, and regulate GEF activity. The resultant ELMO/Dock180/Rac module regulates cytoskeletal reorganization responsible for the engulfment of apoptotic cells, cell migration, and neurite extension. The expression and function of Elmo family proteins in the nervous system, however, are not yet fully understood.

Rubber tail illusion is weakened in Ca-dependent activator protein for secretion 2 (Caps2)-knockout mice.

Body ownership is a fundamental aspect of self-consciousness. Illusion of body ownership is caused by updating body representation through multisensory integration. Synchronous visuotactile stimulation of a hand and rubber hand leads to illusory changes in body ownership in humans, but this is impaired in individuals with autism spectrum disorder (ASD).

Artificial association of memory events by optogenetic stimulation of hippocampal CA3 cell ensembles.

Previous gain-of-function studies using an optogenetic technique showed that manipulation of the hippocampal dentate gyrus or CA1 cell ensembles is important for memory reactivation and to generate synthetic or false memory. However, gain-of-function study manipulating CA3 cell ensembles has not been reported. The CA3 area of the hippocampus comprises a recurrent excitatory circuit, which is thought to be important for the generation of associations among the stored information within one brain region.

Aspects of excitatory/inhibitory synapses in multiple brain regions are correlated with levels of brain-derived neurotrophic factor/neurotrophin-3.

Appropriate synapse formation during development is necessary for normal brain function, and synapse impairment is often associated with brain dysfunction. Brain-derived neurotrophic factor (BDNF) and neurotrophin-3 (NT-3) are key factors in regulating synaptic development. We previously reported that BDNF/NT-3 secretion was enhanced by calcium-dependent activator protein for secretion 2 (CADPS2).

Calcium-dependent activator protein for secretion 2 (CADPS2) deficiency causes abnormal synapse development in hippocampal mossy fiber terminals.

Hippocampal mossy fibers (MFs) project from dentate gyrus granule cells onto the CA2-CA3 region. MF-mediated synaptic transmission plays an important role in hippocampal learning and memory. However, the molecular mechanisms underlying MF synaptic development and subsequent functional organization are not fully understood.

CAPS2 deficiency affects environmental enrichment-induced adult neurogenesis and differentiation/survival of newborn neurons in the hippocampal dentate gyrus.

Hippocampal adult neurogenesis is observed in the subgranular zone of the dentate gyrus (DG), and is associated with hippocampal memory formation and several psychiatric disorders including autism spectrum disorder (ASD). Calcium-dependent activator protein for secretion 2 (CAPS2) is a candidate gene related to ASD, and is highly expressed in the hippocampal DG region, with Caps2 knockout (KO) mice exhibiting ASD-like behavior. Accordingly, CAPS2 is potentially associated with hippocampal adult neurogenesis, the relationship between CAPS2 and adult neurogenesis has not yet been investigated.

The brain-specific RasGEF very-KIND is required for normal dendritic growth in cerebellar granule cells and proper motor coordination.

Very-KIND/Kndc1/KIAA1768 (v-KIND) is a brain-specific Ras guanine nucleotide exchange factor carrying two sets of the kinase non-catalytic C-lobe domain (KIND), and is predominantly expressed in cerebellar granule cells. Here, we report the impact of v-KIND deficiency on dendritic and synaptic growth in cerebellar granule cells in v-KIND knockout (KO) mice. Furthermore, we evaluate motor function in these animals.

CCR5 is a suppressor for cortical plasticity and hippocampal learning and memory.

Although the role of CCR5 in immunity and in HIV infection has been studied widely, its role in neuronal plasticity, learning and memory is not understood. Here, we report that decreasing the function of CCR5 increases MAPK/CREB signaling, long-term potentiation (LTP), and hippocampus-dependent memory in mice, while neuronal CCR5 overexpression caused memory deficits. Decreasing CCR5 function in mouse barrel cortex also resulted in enhanced spike timing dependent plasticity and consequently, dramatically accelerated experience-dependent plasticity.