Lesions to the mediodorsal thalamus, but not orbitofrontal cortex, enhance volatility beliefs linked to paranoia.

Beliefs-attitudes toward some state of the environment-guide action selection and should be robust to variability but sensitive to meaningful change. Beliefs about volatility (expectation of change) are associated with paranoia in humans, but the brain regions responsible for volatility beliefs remain unknown. The orbitofrontal cortex (OFC) is central to adaptive behavior, whereas the magnocellular mediodorsal thalamus (MDmc) is essential for arbitrating between perceptions and action policies.

Mice lacking Ptprd exhibit deficits in goal-directed behavior and female-specific impairments in sensorimotor gating.

Protein Tyrosine Phosphatase receptor type D (PTPRD) is a member of the protein tyrosine phosphatase family that mediates cell adhesion and synaptic specification. Genetic studies have linked Ptprd to several neuropsychiatric phenotypes, including Restless Leg Syndrome (RLS), opioid abuse disorder, and antipsychotic-induced weight gain. Genome-wide association studies (GWAS) of either pediatric obsessive-compulsive traits, or Obsessive-Compulsive Disorder (OCD), have identified loci near PTPRD as genome-wide significant, or strongly suggestive for this trait.

Targeted effects of ketamine on perceptual expectation during mediated learning in rats.

Rationale: While neural correlates of hallucinations are known, the mechanisms have remained elusive. Mechanistic insight is more practicable in animal models, in which causal relationships can be established. Recent work developing animal models of hallucination susceptibility has focused on the genesis of perceptual expectations and perceptual decision-making.

Reinforcement learning detuned in addiction: integrative and translational approaches.

Suboptimal decision-making strategies have been proposed to contribute to the pathophysiology of addiction. Decision-making, however, arises from a collection of computational components that can independently influence behavior. Disruptions in these different components can lead to decision-making deficits that appear similar behaviorally, but differ at the computational, and likely the neurobiological, level.

Saracatinib Fails to Reduce Alcohol-Seeking and Consumption in Mice and Human Participants.

More effective treatments to reduce pathological alcohol drinking are needed. The glutamatergic system and the NMDA receptor (NMDAR), in particular, are implicated in behavioral and molecular consequences of chronic alcohol use, making the NMDAR a promising target for novel pharmacotherapeutics. Ethanol exposure upregulates Fyn, a protein tyrosine kinase that indirectly modulates NMDAR signaling by phosphorylating the NR2B subunit.

MPEP Lowers Binge Drinking in Male and Female C57BL/6 Mice: Relationship with mGlu5/Homer2/Erk2 Signaling.

Background: Metabotropic glutamate receptor 5 (mGlu5) plays an important role in excessive alcohol use and the mGlu5/Homer2/Erk2 signaling pathway has been implicated in binge drinking. The mGlu5 negative allosteric modulator (NAM) 2-methyl-6-(phenylethynyl)pyridine hydrochloride (MPEP) has been shown to reduce binge drinking in male mice, but less is known about its effect on female mice. Here, we sought to determine whether sex differences exists in the effects of MPEP on binge drinking and whether they relate to changes in the MPEP mGlu5/Homer2/Erk2 signaling.

Clinical practice guideline for primary care providers in the management of antidepressant-induced hyperhidrosis: A quality improvement project.

Background: Antidepressant-induced excessive sweating (ADIES) is a side effect that occurs in approximately 22% of patients taking antidepressant medications and can negatively affect patient medication adherence.

Local Problem: Primary care providers may not have adequate knowledge of ADIES management. The aims of this project were to increase primary care provider's overall perceived knowledge related to ADIES, improve confidence in the management of ADIES, and gather input on the perceived usefulness of the initial clinical practice guideline (CPG) for ADIES management.

Managing emotional support animal letters in clinical practice.

The purpose of this brief report is to inform clinical practice and decision making in addressing the increased number of individuals requesting and receiving emotional support animal (ESA) waivers. It is important for providers including nurse practitioners to carefully consider the diagnostic and legal implications of endorsing ESAs. Nurse practitioners should be aware of the legal implications of writing ESA letters before providing them to their patients, understanding that a letter constitutes a determination of a disability.

Ketamine induces immediate and delayed alterations of OCD-like behavior.

Rationale: Obsessive-compulsive disorder (OCD) is a psychiatric disorder characterized by intrusive obsessive thoughts and/or compulsive behaviors. Currently, serotonin reuptake inhibitors (SRIs) provide the only pharmacological monotherapy for OCD, but response rates are insufficient. Ketamine, a noncompetitive NMDA receptor antagonist, was reported to have rapid, sustained therapeutic effects in OCD patients.

Btbd3 expression regulates compulsive-like and exploratory behaviors in mice.

BTB/POZ domain-containing 3 (BTBD3) was identified as a potential risk gene in the first genome-wide association study of obsessive-compulsive disorder (OCD). BTBD3 is a putative transcription factor implicated in dendritic pruning in developing primary sensory cortices. We assessed whether BTBD3 also regulates neural circuit formation within limbic cortico-striato-thalamo-cortical circuits and behaviors related to OCD in mice.

Endocannabinoid contributions to alcohol habits and motivation: Relevance to treatment.

Individuals with alcohol use disorder exhibit compulsive habitual behaviors that are thought to be, in part, a consequence of chronic and persistent use of alcohol. The endocannabinoid system plays a critical role in habit learning and in ethanol self-administration, but the role of this neuromodulatory system in the expression of habitual alcohol seeking is unknown. Here, we investigated the role of the endocannabinoid system in established alcohol habits using contingency degradation in male C57BL/6 mice.

Dissecting the roles of β-arrestin2 and GSK-3 signaling in 5-HT1BR-mediated perseverative behavior and prepulse inhibition deficits in mice.

Serotonin-1B receptors (5-HT1BRs) modulate perseverative behaviors and prepulse inhibition (PPI) in humans and mice. These inhibitory G-protein-coupled receptors signal through a canonical G-protein-coupled pathway that is modulated by GSK-3β, and a noncanonical pathway mediated by the adaptor protein β-arrestin2 (Arrb2). Given the development of biased ligands that differentially affect canonical versus noncanonical signaling, we examined which signaling pathway mediates 5-HT1BR agonist-induced locomotor perseveration and PPI deficits, behavioral phenotypes observed in both obsessive-compulsive disorder (OCD) and autism spectrum disorder (ASD).

When tractography meets tracer injections: a systematic study of trends and variation sources of diffusion-based connectivity.

Tractography is a powerful technique capable of non-invasively reconstructing the structural connections in the brain using diffusion MRI images, but the validation of tractograms is challenging due to lack of ground truth. Owing to recent developments in mapping the mouse brain connectome, high-resolution tracer injection-based axonal projection maps have been created and quickly adopted for the validation of tractography. Previous studies using tracer injections mainly focused on investigating the match in projections and optimal tractography protocols.

The Applicability of Resilience Training to the Mitigation of Trauma-Related Mental Illness in Military Personnel [Formula: see text].

Background: Ongoing participation by the United States in military operations around the world places military personnel at an increased potential for exposure to trauma, which may directly result in an increased risk for mental health issues. It is important to develop and test new approaches to prevent and mitigate the effects of trauma in military personnel. One such area of research is focused on psychological resilience to prevent the sequelae of trauma.

Clinically effective OCD treatment prevents 5-HT1B receptor-induced repetitive behavior and striatal activation.

Rationale: Serotonin-1B receptor (5-HT1BR) agonist treatment induces obsessive-compulsive disorder (OCD)-like behaviors including locomotor stereotypy, prepulse inhibition deficits, and delayed alternation disruptions, which are selectively prevented by clinically effective OCD treatment. However, the role of 5-HT1BRs in modulating other repetitive behaviors or OCD-like patterns of brain activation remains unclear.

Objectives: We assessed the effects of 5-HT1BR agonism on digging, grooming, and open field behaviors in mice.

Cone photoreceptor mosaic disruption associated with Cys203Arg mutation in the M-cone opsin.

Missense mutations in the cone opsins have been identified as a relatively common cause of red/green color vision defects, with the most frequent mutation being the substitution of arginine for cysteine at position 203 (C203R). When the corresponding cysteine is mutated in rhodopsin, it disrupts proper folding of the pigment, causing severe, early onset retinitis pigmentosa. While the C203R mutation has been associated with loss of cone function in color vision deficiency, it is not known what happens to cones expressing this mutant opsin.