The transcription factor VAX1 in VIP neurons of the suprachiasmatic nucleus impacts circadian rhythm generation, depressive-like behavior, and the reproductive axis in a sex-specific manner in mice.

Background: The suprachiasmatic nucleus (SCN) within the hypothalamus is a key brain structure required to relay light information to the body and synchronize cell and tissue level rhythms and hormone release. Specific subpopulations of SCN neurons, defined by their peptide expression, regulate defined SCN output. Here we focus on the vasoactive intestinal peptide (VIP) expressing neurons of the SCN.

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.

Reproductive Deficits Induced by Prenatal Antimüllerian Hormone Exposure Require Androgen Receptor in Kisspeptin Cells.

Polycystic ovary syndrome (PCOS) is a common reproductive disorder characterized by elevated androgens and antimüllerian hormone (AMH). These hormones remain elevated throughout pregnancy, and potential effects of hormone exposure on offspring from women with PCOS remain largely unexplored. Expanding on recent reports of prenatal AMH exposure in mice, we have fully characterized the reproductive consequences of prenatal AMH (pAMH) exposure throughout the lifespan of first- and second-generation offspring of both sexes.

Androgen receptor positively regulates gonadotropin-releasing hormone receptor in pituitary gonadotropes.

Within pituitary gonadotropes, the gonadotropin-releasing hormone receptor (GnRHR) receives hypothalamic input from GnRH neurons that is critical for reproduction. Previous studies have suggested that androgens may regulate GnRHR, although the mechanisms remain unknown. In this study, we demonstrated that androgens positively regulate Gnrhr mRNA in mice.

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.

Activity-Based Anorexia Alters the Expression of BDNF Transcripts in the Mesocorticolimbic Reward Circuit.

Anorexia nervosa (AN) is a complex eating disorder with severe dysregulation of appetitive behavior. The activity-based anorexia (ABA) paradigm is an animal model in which rodents exposed to both running wheels and scheduled feeding develop aspects of AN including paradoxical hypophagia, dramatic weight loss, and hyperactivity, while animals exposed to only one condition maintain normal body weight. Brain-derived neurotrophic factor (BDNF), an activity-dependent modulator of neuronal plasticity, is reduced in the serum of AN patients, and is a known regulator of feeding and weight maintenance.

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.

Effects of chronic fluoxetine treatment on serotonin 1B receptor-induced deficits in delayed alternation.

Rationale: Obsessive-compulsive disorder (OCD) patients show overactivation of the orbitofrontal cortex and deficits in cognitive tasks that require proper orbitofrontal functioning including delayed alternation tests of spatial working memory. We recently showed that OCD-like behavior is induced in mice by activating orbitofrontal serotonin 1B receptors (5-HT1Bs). However, the role of 5-HT1Bs in delayed alternation remains unclear.