Persistent enhancement of basolateral amygdala-dorsomedial striatum synapses causes compulsive-like behaviors in mice.

Compulsive behaviors are observed in a range of psychiatric disorders, however the neural substrates underlying the behaviors are not clearly defined. Here we show that the basolateral amygdala-dorsomedial striatum (BLA-DMS) circuit activation leads to the manifestation of compulsive-like behaviors. We revealed that the BLA neurons projecting to the DMS, mainly onto dopamine D1 receptor-expressing neurons, largely overlap with the neuronal population that responds to aversive predator stress, a widely used anxiogenic stressor.

Orexinergic neurons modulate stress coping responses in mice.

Stress is a critical precipitating factor for major depression. However, individual responses to the same stressor vary widely, possibly owing to individual variations in stress resilience. Nevertheless, the factors that determine stress susceptibility and resilience remain poorly understood.

Myristoylation-dependent palmitoylation of cyclin Y modulates long-term potentiation and spatial learning.

Many psychiatric disorders accompany deficits in cognitive functions and synaptic plasticity, and abnormal lipid modifications of neuronal proteins are associated with their pathophysiology. Lipid modifications, including palmitoylation and myristoylation, play crucial roles in the subcellular localization and trafficking of proteins. Cyclin Y (CCNY), enriched in the postsynaptic compartment, acts as an inhibitory modulator of functional and structural long-term potentiation (LTP) in the hippocampal neurons.

Dynamic Changes in the Bridging Collaterals of the Basal Ganglia Circuitry Control Stress-Related Behaviors in Mice.

The basal ganglia network has been implicated in the control of adaptive behavior, possibly by integrating motor learning and motivational processes. Both positive and negative reinforcement appear to shape our behavioral adaptation by modulating the function of the basal ganglia. Here, we examined a transgenic mouse line (G2CT) in which synaptic transmissions onto the medium spiny neurons (MSNs) of the basal ganglia are depressed.

CRMP2 mediates GSK3β actions in the striatum on regulating neuronal structure and mania-like behavior.

Background: Genetic and physiological studies have implicated the striatum in bipolar disorder (BD). Although Glycogen synthase kinase 3 beta (GSK3β) has been suggested to play a role in the pathophysiology of BD since it is inhibited by lithium, it remains unknown how GSK3β activity might be involved. Therefore we examined the functional roles of GSK3β and one of its substrates, CRMP2, within the striatum.

Dopamine D2 receptor-mediated circuit from the central amygdala to the bed nucleus of the stria terminalis regulates impulsive behavior.

Impulsivity is closely associated with addictive disorders, and changes in the brain dopamine system have been proposed to affect impulse control in reward-related behaviors. However, the central neural pathways through which the dopamine system controls impulsive behavior are still unclear. We found that the absence of the D2 dopamine receptor (D2R) increased impulsive behavior in mice, whereas restoration of D2R expression specifically in the central amygdala (CeA) of D2R knockout mice ( normalized their enhanced impulsivity.

Modulating the Voltage-sensitivity of a Genetically Encoded Voltage Indicator.

Saturation mutagenesis was performed on a single position in the voltage-sensing domain (VSD) of a genetically encoded voltage indicator (GEVI). The VSD consists of four transmembrane helixes designated S1-S4. The V220 position located near the plasma membrane/extracellular interface had previously been shown to affect the voltage range of the optical signal.

Optogenetic Monitoring of Synaptic Activity with Genetically Encoded Voltage Indicators.

The age of genetically encoded voltage indicators (GEVIs) has matured to the point that changes in membrane potential can now be observed optically in vivo. Improving the signal size and speed of these voltage sensors has been the primary driving forces during this maturation process. As a result, there is a wide range of probes using different voltage detecting mechanisms and fluorescent reporters.

Linker length and fusion site composition improve the optical signal of genetically encoded fluorescent voltage sensors.

Several genetically encoded fluorescent sensors of voltage were created by systematically truncating the length of the linker sequence between the voltage-sensing domain and the position of the fluorescent protein, Super Ecliptic A227D. In addition to varying the length, the amino acid composition at the fusion site for the fluorescent protein was modified. Both linker length and amino acid composition affected the size and voltage sensitivity of the optical signal.

Altered trafficking of α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid-type glutamate receptors (AMPARs) in the striatum leads to behavioral changes in emotional responses.

The striatum receives and integrates multiple inputs from diverse areas in the brain and plays a critical role in the regulation of motor activity. However, whether the striatum is involved in the alteration of behavior in the presence of emotional challenges is unknown. Here, we examined whether alterations in the surface expression of α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid-type glutamate receptors (AMPARs) in the dorsal striatum would affect anxiety-related behaviors.

Association of brain-derived neurotrophic factor DNA methylation and reduced white matter integrity in the anterior corona radiata in major depression.

Considerable evidence suggests a crucial role for the epigenetic regulation of brain-derived neurotrophic factor (BDNF) in the pathophysiology of major depressive disorder (MDD). However, the relationship between BDNF DNA methylation and white matter (WM) integrity in MDD has not yet been investigated. In the current study, we examined the association between the DNA methylation status of the BDNF promoter region and WM integrity in MDD.

Orexin administration to mice that underwent chronic stress produces bimodal effects on emotion-related behaviors.

Orexin plays diverse roles in regulating behaviors, such as sleep and wake, reward processing, arousal, and stress and anxiety. The orexin system may accomplish these multiple tasks through its complex innervations throughout the brain. The emerging evidence indicates a role of orexin in emotional behaviors; however, most of the previous studies have investigated the function of orexin in naïve animals.

Optogenetics reveals a role for accumbal medium spiny neurons expressing dopamine D2 receptors in cocaine-induced behavioral sensitization.

Long-lasting, drug-induced adaptations within the nucleus accumbens (NAc) have been proposed to contribute to drug-mediated addictive behaviors. Here we have used an optogenetic approach to examine the role of NAc medium spiny neurons (MSNs) expressing dopamine D2 receptors (D2Rs) in cocaine-induced behavioral sensitization. Adeno-associated viral vectors encoding channelrhodopsin-2 (ChR2) were delivered into the NAc of D2R-Cre transgenic mice.

Snx14 regulates neuronal excitability, promotes synaptic transmission, and is imprinted in the brain of mice.

Genomic imprinting describes an epigenetic process through which genes can be expressed in a parent-of-origin-specific manner. The monoallelic expression of imprinted genes renders them particularly susceptible to disease causing mutations. A large proportion of imprinted genes are expressed in the brain, but little is known about their functions.

The expression of PHO92 is regulated by Gcr1, and Pho92 is involved in glucose metabolism in Saccharomyces cerevisiae.

Ydr374c (Pho92) contains a YTH domain in its C-terminal region and is a human YTHDF2 homologue. Previously, we reported that Pho92 regulates phosphate metabolism by regulating PHO4 mRNA stability. In this study, we found that growth of the ∆pho92 strain on SG media was slower than that of the wild type and that PHO92 expression was up-regulated by non-fermentable carbon sources, such as ethanol and glycerol, but not by fermentable carbon sources.

Development of a novel screening system for allatostatin receptor agonists in search of new candidate insect growth regulators.

Allatostatins (ASTs) are insect neuropeptide hormones that regulate diverse physiological functions, including feeding, growth and development, and reproduction. Therefore, regulation of allatostatin receptor (AstR) activity can be an effective tool for controlling insect growth and proliferation. Here, we describe a novel screening system using a mammalian cell line in which AstR is ectopically expressed, combined with fluorescence-based measurements of the membrane potential.

Remodeling of the dendritic structure of the striatal medium spiny neurons accompanies behavioral recovery in a mouse model of Parkinson's disease.

Medium spiny neurons (MSNs) are the major type of neurons found in the striatum. The dendritic spines on these cells contain glutamatergic synaptic contacts between the cortex (or the thalamus) and the striatum. The complexity of the dendritic structure of MSNs may therefore reflect the functional status of the basal ganglia because the striatum is the major input structure in which signals from different regions are integrated.

Different locomotor sensitization responses to repeated cocaine injections are associated with differential phosphorylation of GluA1 in the dorsomedial striatum of adult rats.

Behavioral sensitization to psychostimulants reflects neural adaptation, which might share a common mechanism with drug addiction. Outbred male rats show different locomotor sensitization responses to cocaine, and cocaine also produces varied addictive progress in humans. We investigated whether differences in the induction of sensitization would affect the long-term persistence of sensitized locomotor activity, and we sought to determine the molecular basis for the variability in sensitization.

Basal blood corticosterone level is correlated with susceptibility to chronic restraint stress in mice.

Corticosterone is released in response to stress and manifests as various bodily stress responses in rodents. While corticosterone reflects acute adaptive responses, how the basal steady-state corticosterone level relates to the subsequent stress response is largely unknown. Here, we investigated how basal corticosterone levels can affect the susceptibility to chronic restraint stress in mice.

Channel-mediated astrocytic glutamate release via Bestrophin-1 targets synaptic NMDARs.

Background: Astrocytes regulate neuronal excitability and synaptic activity by releasing gliotransmitters such as glutamate. Our recent study demonstrated that astrocytes release glutamate upon GPCR activation via Ca2+ activated anion channel, Bestrophin-1 (Best1). The target of Best1-mediated astrocytic glutamate has been shown to be the neuronal NMDA receptors (NMDAR).

Administration of clomipramine to neonatal mice alters stress response behavior and serotonergic gene expressions in adult mice.

Early life exposure to antidepressants frequently occurs when pregnant mothers take the medication during late pregnancy. Previous studies in animal models have shown that early exposure to certain antidepressants can alter some behaviors in adulthood. We examined whether the administration of clomipramine, a serotonin reuptake inhibitor, to neonatal mice could result in depression-related behavioral alterations in adult mice.

Essential role for a long-term depression mechanism in ocular dominance plasticity.

The classic example of experience-dependent cortical plasticity is the ocular dominance (OD) shift in visual cortex after monocular deprivation (MD). The experimental model of homosynaptic long-term depression (LTD) was originally introduced to study the mechanisms that could account for deprivation-induced loss of visual responsiveness. One established LTD mechanism is a loss of sensitivity to the neurotransmitter glutamate caused by internalization of postsynaptic alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid receptors (AMPARs).

Ras-guanine nucleotide-releasing factor 1 (Ras-GRF1) controls activation of extracellular signal-regulated kinase (ERK) signaling in the striatum and long-term behavioral responses to cocaine.

Background: Ras-extracellular signal-regulated kinase (Ras-ERK) signaling is central to the molecular machinery underlying cognitive functions. In the striatum, ERK1/2 kinases are co-activated by glutamate and dopamine D1/5 receptors, but the mechanisms providing such signaling integration are still unknown. The Ras-guanine nucleotide-releasing factor 1 (Ras-GRF1), a neuronal specific activator of Ras-ERK signaling, is a likely candidate for coupling these neurotransmitter signals to ERK kinases in the striatonigral medium spiny neurons (MSN) and for modulating behavioral responses to drug abuse such as cocaine.

Microbiological examination of vegetable seed sprouts in Korea.

Sprouted vegetable seeds used as food have been implicated as sources of outbreaks of Salmonella and Escherichia coli O157:H7 infections. We profiled the microbiological quality of sprouts and seeds sold at retail shops in Seoul, Korea. Ninety samples of radish sprouts and mixed sprouts purchased at department stores, supermarkets, and traditional markets and 96 samples of radish, alfalfa, and turnip seeds purchased from online stores were analyzed to determine the number of total aerobic bacteria (TAB) and molds or yeasts (MY) and the incidence of Salmonella, E.

AMPA receptor trafficking in the dorsal striatum is critical for behavioral sensitization to cocaine in juvenile mice.

Advances in understanding the neurobiology of addiction indicate that not only dopaminergic neurotransmissions but also glutamatergic neurotransmissions within the mesolimbic system play important roles. While the role for the nucleus accumbens (NAc) shell and core in addiction has been extensively studied, the function of the dorsal striatum is not clear. Here, we demonstrate that repeated cocaine injections cause increases in surface-expressed AMPA receptors in the dorsal striatum.