Limbic oxytocin receptor expression alters molecular signaling and social avoidance behavior in female prairie voles ().

Introduction: The social defeat paradigm is the most representative animal model to study social anxiety disorder (SAD) and its underlying neuronal mechanisms. We have previously reported that defeat progressively reduces oxytocin receptors (OXTR) in limbic regions of the brain over an eight-week period in female prairie voles (). Oxytocin receptors activate the mitogen-activated protein kinase (MAPK) pathway, which has been previously associated with the anxiolytic effects of oxytocin.

Natural variation in oxytocin receptor signaling causes widespread changes in brain transcription: a link to the natural killer gene complex.

Oxytocin (OXT) is a highly conserved neuropeptide that modulates social cognition, and variation in its receptor gene () is associated with divergent social phenotypes. The cellular mechanisms connecting genotype to social phenotype remain obscure. We exploit an association between polymorphisms and striatal-specific OXTR density in prairie voles to investigate how OXTR signaling influences the brain transcriptome.

An AAV-CRISPR/Cas9 strategy for gene editing across divergent rodent species: Targeting neural oxytocin receptors as a proof of concept.

A major issue in neuroscience is the poor translatability of research results from preclinical studies in animals to clinical outcomes. Comparative neuroscience can overcome this barrier by studying multiple species to differentiate between species-specific and general mechanisms of neural circuit functioning. Targeted manipulation of neural circuits often depends on genetic dissection, and use of this technique has been restricted to only a few model species, limiting its application in comparative research.

Social experience alters oxytocinergic modulation in the nucleus accumbens of female prairie voles.

Social relationships are dynamic and evolve with shared and personal experiences. Whether the functional role of social neuromodulators also evolves with experience to shape the trajectory of relationships is unknown. We utilized pair bonding in the socially monogamous prairie vole as an example of socio-sexual experience that dramatically alters behaviors displayed toward other individuals.

Striatal Astrocytes Shape Behavioral Flexibility via Regulation of the Glutamate Transporter EAAT2.

Background: Striatal circuits must be modulated for behavioral flexibility, the ability to adapt to environmental changes. Striatal astrocytes contribute to circuit neuromodulation by controlling the activity of ambient neurotransmitters. In particular, extracellular glutamate levels are tightly controlled by the astrocytic glutamate transporter EAAT2, influencing synaptic functioning and neural network activity.

Oxytocin, vasopressin and social behavior in the age of genome editing: A comparative perspective.

Behavioral neuroendocrinology has a rich history of using diverse model organisms to elucidate general principles and evolution of hormone-brain-behavior relationships. The oxytocin and vasopressin systems have been studied in many species, revealing their role in regulating social behaviors. Oxytocin and vasopressin receptors show remarkable species and individual differences in distribution in the brain that have been linked to diversity in social behaviors.

Deletion of astrocytic BMAL1 results in metabolic imbalance and shorter lifespan in mice.

Disruption of the circadian cycle is strongly associated with metabolic imbalance and reduced longevity in humans. Also, rodent models of circadian arrhythmia, such as the constitutive knockout of the clock gene Bmal1, leads to metabolic disturbances and early death. Although astrocyte clock regulates molecular and behavioral circadian rhythms, its involvement in the regulation of energy balance and lifespan is unknown.

A light-gated potassium channel for sustained neuronal inhibition.

Currently available inhibitory optogenetic tools provide short and transient silencing of neurons, but they cannot provide long-lasting inhibition because of the requirement for high light intensities. Here we present an optimized blue-light-sensitive synthetic potassium channel, BLINK2, which showed good expression in neurons in three species. The channel is activated by illumination with low doses of blue light, and in our experiments it remained active over (tens of) minutes in the dark after the illumination was stopped.

Diet-induced neuropeptide expression: feasibility of quantifying extended and highly charged endogenous peptide sequences by selected reaction monitoring.

Understanding regulation and action of endogenous peptides, especially neuropeptides, which serve as inter- and intracellular signal transmitters, is key in understanding a variety of functional processes, such as energy balance, memory, circadian rhythm, drug addiction, etc. Therefore, accurate and reproducible quantification of these bioactive endogenous compounds is highly relevant. The biosynthesis of endogenous peptides, involving multiple possible trimming and modification events, hinders the de novo prediction of the active peptide sequences, making MS-based measurements very valuable in determining the actual active compounds.

Young, active and well-connected: adult-born neurons in the zebra finch are activated during singing.

Neuronal replacement in the pallial song control nucleus HVC of adult zebra finches constitutes an interesting case of homeostatic plasticity; in spite of continuous addition and attrition of neurons in ensembles that code song elements, adult song remains remarkably invariant. New neurons migrate into HVC and later synapse with their target, arcopallial song nucleus RA (HVCRA). New HVCRA neurons respond to auditory stimuli (in anaesthetised animals), but whether and when they become functionally active during singing is unknown.

The obesity-associated gene Negr1 regulates aspects of energy balance in rat hypothalamic areas.

Neural growth regulator 1 (Negr1) is among the first common variants that have been associated with the regulation of body mass index. Using AAV technology directed to manipulate Negr1 expression in vivo, we find that decreased expression of Negr1 in periventricular hypothalamic areas leads to increases in body weight, presumably via increased food intake. Moreover, we observed that both increased and decreased levels of Negr1 lead to reduced locomotor activity and body temperature.

Recombinant adeno-associated virus: efficient transduction of the rat VMH and clearance from blood.

To promote the efficient and safe application of adeno-associated virus (AAV) vectors as a gene transfer tool in the central nervous system (CNS), transduction efficiency and clearance were studied for serotypes commonly used to transfect distinct areas of the brain. As AAV2 was shown to transduce only small volumes in several brain regions, this study compares the transduction efficiency of three AAV pseudotyped vectors, namely AAV2/1, AAV2/5 and AAV2/8, in the ventromedial nucleus of the hypothalamus (VMH). No difference was found between AAV2/1 and AAV2/5 in transduction efficiency.

Combined use of the canine adenovirus-2 and DREADD-technology to activate specific neural pathways in vivo.

We here describe a technique to transiently activate specific neural pathways in vivo. It comprises the combined use of a CRE-recombinase expressing canine adenovirus-2 (CAV-2) and an adeno-associated virus (AAV-hSyn-DIO-hM3D(Gq)-mCherry) that contains the floxed inverted sequence of the designer receptor exclusively activated by designer drugs (DREADD) hM3D(Gq)-mCherry. CAV-2 retrogradely infects projection neurons, which allowed us to specifically express hM3D(Gq)-mCherry in neurons that project from the ventral tegmental area (VTA) to the nucleus accumbens (Acb), the majority of which were dopaminergic.

Cannabinoid, melanocortin and opioid receptor expression on DRD1 and DRD2 subpopulations in rat striatum.

The striatum harbors two neuronal populations that enable action selection. One population represents the striatonigral pathway, expresses the dopamine receptor D1 (DRD1) and promotes the execution of motor programs, while the other population represents the striatopallidal pathway, expresses the dopamine receptor D2 (DRD2) and suppresses voluntary activity. The two populations integrate distinct sensorimotor, cognitive, and emotional information streams and their combined activity enables the selection of adaptive behaviors.

AAV-mediated gene transfer of the obesity-associated gene Etv5 in rat midbrain does not affect energy balance or motivated behavior.

Several genome-wide association studies have implicated the transcription factor E-twenty- six version 5 (Etv5) in the regulation of body mass index. Further substantiating the role of Etv5 in feeding behavior are the findings that targeted disruption of Etv5 in mice leads to decreased body weight gain and that expression of Etv5 is decreased in the ventral tegmental area and substantia nigra pars compacta (VTA/SNpc) after food restriction. As Etv5 has been suggested to influence dopaminergic neurotransmission by driving the expression of genes that are responsible for the synthesis and release of dopamine, we investigated if expression levels of Etv5 are dependent on nutritional state and subsequently influence the expression levels of tyrosine hydroxylase.

Profiling of diet-induced neuropeptide changes in rat brain by quantitative mass spectrometry.

Neuropeptides are intercellular signal transmitters that play key roles in modulation of many behavioral and physiological processes. Neuropeptide signaling in several nuclei in the hypothalamus contributes to the control of food intake. Additionally, food intake regulation involves neuropeptide signaling in the reward circuitry in the striatum.

Nutritional state affects the expression of the obesity-associated genes Etv5, Faim2, Fto, and Negr1.

Obesity is a risk factor for type II diabetes, atherosclerosis, and some forms of cancer. Variation in common measures of obesity (e.g.

Genomewide analysis of rat barrel cortex reveals time- and layer-specific mRNA expression changes related to experience-dependent plasticity.

Because of its anatomical organization, the rodent whisker-to-barrel system is an ideal model to study experience-dependent plasticity. Manipulation of sensory input causes changes in the properties of the barrels at the physiological, structural, and functional levels. However, much less is known about the molecular events underlying these changes.

Together or alone?: foraging strategies in Caenorhabditis elegans.

A central goal in Life Sciences is to understand how genes encode behaviour and how environmental factors influence the expression of the genes concerned. To reach this goal a combined ecological, molecular biological and physiological approach is required in combination with a suitable model organism. Such an approach allows the elucidation of all parts of the complicated chain of events that lead from induction of gene expression to behaviour, i.