Rhythms, Reward, and Blues: Consequences of Circadian Photoperiod on Affective and Reward Circuit Function.

Circadian disruptions, along with altered affective and reward states, are commonly associated with psychiatric disorders. In addition to genetics, the enduring influence of environmental factors in programming neural networks is of increased interest in assessing the underpinnings of mental health. The duration of daylight or photoperiod is known to impact both the serotonin and dopamine systems, which are implicated in mood and reward-based disorders.

Stimulus Feature-Specific Information Flow Along the Columnar Cortical Microcircuit Revealed by Multivariate Laminar Spiking Analysis.

Most of the mammalian neocortex is comprised of a highly similar anatomical structure, consisting of a granular cell layer between superficial and deep layers. Even so, different cortical areas process different information. Taken together, this suggests that cortex features a canonical functional microcircuit that supports region-specific information processing.

Approaches to Understanding Multisensory Dysfunction in Autism Spectrum Disorder.

Abnormal sensory responses are a DSM-5 symptom of autism spectrum disorder (ASD), and research findings demonstrate altered sensory processing in ASD. Beyond difficulties with processing information within single sensory domains, including both hypersensitivity and hyposensitivity, difficulties in multisensory processing are becoming a core issue of focus in ASD. These difficulties may be targeted by treatment approaches such as "sensory integration," which is frequently applied in autism treatment but not yet based on clear evidence.

Extracellular heparan sulfate proteoglycans and glycan-binding lectins orchestrate -synaptic signaling.

The exceedingly narrow synaptic cleft (<20 nm) and adjacent perisynaptic extracellular space contain an astonishing array of secreted and membrane-anchored glycoproteins. A number of these extracellular molecules regulate intercellular -synaptic signaling by binding to ligands, acting as co-receptors or modulating ligand-receptor interactions. Recent work has greatly expanded our understanding of extracellular proteoglycan and glycan-binding lectin families as key regulators of intercellular signaling at the synapse.

Huntington's disease genotype suppresses global manganese-responsive processes in pre-manifest and manifest YAC128 mice.

Manganese (Mn) is an essential micronutrient required for the proper function of several enzymes. Accumulating evidence demonstrates a selective decrease of bioavailable Mn in vulnerable cell types of Huntington's Disease (HD), an inherited progressive neurodegenerative disorder with no cure. Amelioration of underlying pathophysiology, such as alterations in Mn-dependent biology, may be therapeutic.

Amiodarone Alters Cholesterol Biosynthesis through Tissue-Dependent Inhibition of Emopamil Binding Protein and Dehydrocholesterol Reductase 24.

Amiodarone is prescribed for the treatment and prevention of irregular heartbeats. Although effective in clinical practice, the long-term use of amiodarone has many unwanted side effects, including cardiac, pulmonary, hepatic, and neurological toxicities. Our objective was to elucidate effects of amiodarone exposure on the cholesterol metabolism in cultured neuronal and non-neuronal cells and in individuals taking amiodarone.

α-adrenergic heteroreceptors are required for stress-induced reinstatement of cocaine conditioned place preference.

The α-adrenergic receptor (α-AR) agonist guanfacine has been investigated as a potential treatment for substance use disorders. While decreasing stress-induced reinstatement of cocaine seeking in animal models and stress-induced craving in human studies, guanfacine has not been reported to decrease relapse rates. Although guanfacine engages α-AR autoreceptors, it also activates excitatory G-coupled heteroreceptors in the bed nucleus of the stria terminalis (BNST), a key brain region in driving stress-induced relapse.

Carrier of Wingless (Cow) Regulation of Neuromuscular Junction Development.

The first Wnt signaling ligand discovered, Wingless [Wg (Wnt1 in mammals)], plays critical roles in neuromuscular junction (NMJ) development, regulating synaptic architecture, and function. Heparan sulfate proteoglycans (HSPGs), consisting of a core protein with heparan sulfate (HS) glycosaminoglycan (GAG) chains, bind to Wg ligands to control both extracellular distribution and intercellular signaling function. HSPGs previously shown to regulate Wg trans-synaptic signaling at the NMJ include the glypican Dally-like protein (Dlp) and perlecan Terribly Reduced Optic Lobes (Trol).

Neuronal L-Type Calcium Channel Signaling to the Nucleus Requires a Novel CaMKIIα-Shank3 Interaction.

The activation of neuronal plasma membrane Ca channels stimulates many intracellular responses. Scaffolding proteins can preferentially couple specific Ca channels to distinct downstream outputs, such as increased gene expression, but the molecular mechanisms that underlie the exquisite specificity of these signaling pathways are incompletely understood. Here, we show that complexes containing CaMKII and Shank3, a postsynaptic scaffolding protein known to interact with L-type calcium channels (LTCCs), can be specifically coimmunoprecipitated from mouse forebrain extracts.

Anxiety during abstinence from alcohol: A systematic review of rodent and human evidence for the anterior insula's role in the abstinence network.

Alcohol Use Disorder (AUD) is a chronic, relapsing disease that impacts almost a third of Americans. Despite effective treatments for attaining sobriety, the majority of patients relapse within a year, making relapse a substantial barrier to long-term treatment success. A major factor contributing to relapse is heightened negative affect that results from the combination of abstinence-related increases in stress-reactivity and decreases in reward sensitivity.

CaMKIIα phosphorylation of Shank3 modulates ABI1-Shank3 interaction.

Protein-protein interactions can be modulated by phosphorylation of either binding partner, thereby altering subcellular localization and/or physiological function. Shank3, a master postsynaptic scaffolding protein that controls the developmental maturation of excitatory synapses, was recently shown to be phosphorylated by Protein Kinase A (PKA) at Ser685 in vivo. Mutation of Shank3 Ser685 was shown to modulate the binding of Abelson interactor 1 (ABI1), a component of the WAVE regulatory complex for actin remodeling, but a direct effect of Ser685 phosphorylation on ABI1 binding was not investigated.

Early Diagnosis in Prader-Willi Syndrome Reduces Obesity and Associated Co-Morbidities.

Prader-Willi syndrome (PWS) is an imprinting genetic disorder characterized by lack of expression of genes on the paternal chromosome 15q11-q13 region. Growth hormone (GH) replacement positively influences stature and body composition in PWS. Our hypothesis was that early diagnosis delays onset of obesity in PWS.

A placebo-controlled trial of folic acid and betaine in identical twins with Angelman syndrome.

Background: Angelman syndrome (AS) is a neurodevelopmental disorder that is caused by maternal genetic deficiency of a gene that encodes E6-AP ubiquitin-protein ligase (gene symbol UBE3A) mapping to chromosome 15q11-q13. AS leads to stiff and jerky gait, excess laughter, seizures, and severe intellectual disability. In some parts of the brain, the paternally inherited UBE3A gene is subject to genomic imprinting by the action of the UBE3A-antisense transcript (UBE3A-ATS) on the paternally inherited allele.

Profiles and trajectories of impaired social cognition in people with Prader-Willi syndrome.

Introduction: People with Prader-Willi syndrome (PWS) have a distinctive behavioral phenotype that includes intellectual disability, compulsivity, inattention, inflexibility and insistence on sameness. Inflexibility and inattention are at odds with the cognitive flexibility and attention to social cues needed to accurately perceive the social world, and implicate problems in social cognition. This study assessed two social cognition domains in people with PWS; emotion recognition and social perception.

Driving the Downward Spiral: Alcohol-Induced Dysregulation of Extended Amygdala Circuits and Negative Affect.

Alcohol use disorder (AUD) afflicts a large number of individuals, families, and communities globally. Affective disturbances, including stress, depression, and anxiety, are highly comorbid with AUD, contributing in some cases to initial alcohol use and continued use. Negative affect has a particularly strong influence on the withdrawal/abstinence stage of addiction as individuals with AUD frequently report stressful events, depression, and anxiety as key factors for relapse.

Endocannabinoid Signaling in the Central Amygdala and Bed Nucleus of the Stria Terminalis: Implications for the Pathophysiology and Treatment of Alcohol Use Disorder.

High rates of relapse are a chronic and debilitating obstacle to effective treatment of alcohol use disorder (AUD); however, no effective treatments are available to treat symptoms induced by protracted abstinence. In the first part of this 2-part review series, we examine the literature supporting the effects of alcohol exposure within the extended amygdala (EA) neural circuitry. In Part 2, we focus on a potential way to combat negative affect associated with AUD, by exploring the therapeutic potential of the endogenous cannabinoid (eCB) system.

Birth seasonality studies in a large Prader-Willi syndrome cohort.

Prader-Willi syndrome (PWS) is generally due to sporadic paternal deletions of the chromosome 15q11-q13 region followed by maternal disomy 15. Advanced maternal age is more commonly seen in those with maternal disomy 15. Environmental factors (e.

Chronic Intermittent Ethanol and Acute Stress Similarly Modulate BNST CRF Neuron Activity via Noradrenergic Signaling.

Background: Relapse is a critical barrier to effective long-term treatment of alcoholism, and stress is often cited as a key trigger to relapse. Numerous studies suggest that stress-induced reinstatement to drug-seeking behaviors is mediated by norepinephrine (NE) and corticotropin-releasing factor (CRF) signaling interactions in the bed nucleus of the stria terminalis (BNST), a brain region critical to many behavioral and physiologic responses to stressors. Here, we sought to directly examine the effects of NE on BNST CRF neuron activity and determine whether these effects may be modulated by chronic intermittent EtOH (CIE) exposure or a single restraint stress.

Sequential Photoperiodic Programing of Serotonin Neurons, Signaling and Behaviors During Prenatal and Postnatal Development.

Early life stimuli during critical developmental time frames have been linked to increased risk for neurodevelopmental disorders later in life. The serotonergic system of the brain is implicated in mood disorders and is impacted by the duration of daylight, or photoperiod. Here we sought to investigate sensitive periods of prenatal and postnatal development for photoperiodic programming of DRN serotonin neurons, midbrain serotonin and metabolite levels along with affective behaviors in adolescence (P30) or adulthood (P50).

Striatal Cholesterol Precursors Are Altered with Age in Female Huntington's Disease Model Mice.

Background: Cholesterol is necessary for proper neurodevelopment and neuronal health. The brain relies on neural and astrocytic de novo cholesterol synthesis. Huntington's disease presents with altered levels of cholesterol precursors however it is unknown when the disruption in this molecular pathway occurs and whether Manganese (Mn) may alter these metabolic alterations.

Desmosterolosis and desmosterol homeostasis in the developing mouse brain.

Cholesterol serves as a building material for cellular membranes and plays an important role in cellular metabolism. The brain relies on its own cholesterol biosynthesis, which starts during embryonic development. Cholesterol is synthesized from two immediate precursors, desmosterol and 7-dehydrocholesterol (7-DHC).

BMP-dependent synaptic development requires Abi-Abl-Rac signaling of BMP receptor macropinocytosis.

Retrograde BMP trans-synaptic signaling is essential for synaptic development. Despite the importance of endocytosis-regulated BMP receptor (BMPR) control of this developmental signaling, the mechanism remains unknown. Here, we provide evidence that Abelson interactor (Abi), a substrate for Abl kinase and component of the SCAR/WAVE complex, links Abl and Rac1 GTPase signaling to BMPR macropinocytosis to restrain BMP-mediated synaptic development.

Effect of competing noise on cortical auditory evoked potentials elicited by speech sounds in 7- to 25-year-old listeners.

Child listeners have particular difficulty with speech perception when competing speech noise is present; this challenge is often attributed to their immature top-down processing abilities. The purpose of this study was to determine if the effects of competing speech noise on speech-sound processing vary with age. Cortical auditory evoked potentials (CAEPs) were measured during an active speech-syllable discrimination task in 58 normal-hearing participants (age 7-25 years).

Spoken word processing in Rett syndrome: Evidence from event-related potentials.

This study examined the feasibility of using auditory event-related potentials to evaluate spoken word processing during passive listening in girls with Rett syndrome (n = 11) and typical peers (n = 33), age 4-12 years. The typical group demonstrated the expected pattern of more negative amplitudes within 200-500 ms in response to words than nonwords at left temporal sites. In participants with Rett syndrome, word-nonword differentiation was observed at the right temporal sites.

α-Adrenergic Receptor Activation Decreases Parabrachial Nucleus Excitatory Drive onto BNST CRF Neurons and Reduces Their Activity .

Stress contributes to numerous psychiatric disorders. Corticotropin releasing factor (CRF) signaling and CRF neurons in the bed nucleus of the stria terminalis (BNST) drive negative affective behaviors, thus agents that decrease activity of these cells may be of therapeutic interest. Here, we show that acute restraint stress increases cFos expression in CRF neurons in the mouse dorsal BNST, consistent with a role for these neurons in stress-related behaviors.