Frontal-Sensory Cortical Projections Become Dispensable for Attentional Performance Upon a Reduction of Task Demand in Mice.

Top-down attention is a dynamic cognitive process that facilitates the detection of the task-relevant stimuli from our complex sensory environment. A neural mechanism capable of deployment under specific task-demand conditions would be crucial to efficiently control attentional processes and improve promote goal-directed attention performance during fluctuating attentional demand. Previous studies have shown that frontal top-down neurons projecting from the anterior cingulate area (ACA) to the visual cortex (VIS; ACA) are required for visual attentional behavior during the 5-choice serial reaction time task (5CSRTT) in mice.

Using Postmarket Surveillance to Assess Safety-Related Events in a Digital Rehabilitation App (Kaia App): Observational Study.

Background: Low back pain (LBP) affects nearly 4 out of 5 individuals during their lifetime and is the leading cause of disability globally. Digital therapeutics are emerging as effective treatment options for individuals experiencing LBP. Despite the growth of evidence demonstrating the benefits of these therapeutics in reducing LBP and improving functional outcomes, little data has been systematically collected on their safety profiles.

Chemogenetic suppression of anterior cingulate cortical neurons projecting to the visual cortex disrupts attentional behavior in mice.

Aim: Attention is a goal-directed cognitive process that facilitates the detection of task-relevant sensory stimuli from dynamic environments. Anterior cingulate cortical area (ACA) is known to play a key role in attentional behavior, but the specific circuits mediating attention remain largely unknown. As ACA modulates sensory processing in the visual cortex (VIS), we aim to test a hypothesis that frontal top-down neurons projecting from ACA to VIS (ACA ) contributes to visual attention behavior through chemogenetic approach.

Nicotinic regulation of local and long-range input balance drives top-down attentional circuit maturation.

Cognitive function depends on frontal cortex development; however, the mechanisms driving this process are poorly understood. Here, we identify that dynamic regulation of the nicotinic cholinergic system is a key driver of attentional circuit maturation associated with top-down frontal neurons projecting to visual cortex. The top-down neurons receive robust cholinergic inputs, but their nicotinic tone decreases following adolescence by increasing expression of a nicotinic brake, shifts a balance between local and long-range inputs onto top-down frontal neurons following adolescence and promotes the establishment of attentional behavior in adulthood.

Post-error recruitment of frontal sensory cortical projections promotes attention in mice.

The frontal cortex, especially the anterior cingulate cortex area (ACA), is essential for exerting cognitive control after errors, but the mechanisms that enable modulation of attention to improve performance after errors are poorly understood. Here we demonstrate that during a mouse visual attention task, ACA neurons projecting to the visual cortex (VIS; ACA neurons) are recruited selectively by recent errors. Optogenetic manipulations of this pathway collectively support the model that rhythmic modulation of ACA neurons in anticipation of visual stimuli is crucial for adjusting performance following errors.

A prefrontal-paraventricular thalamus circuit requires juvenile social experience to regulate adult sociability in mice.

Juvenile social isolation reduces sociability in adulthood, but the underlying neural circuit mechanisms are poorly understood. We found that, in male mice, 2 weeks of social isolation immediately following weaning leads to a failure to activate medial prefrontal cortex neurons projecting to the posterior paraventricular thalamus (mPFC→pPVT) during social exposure in adulthood. Chemogenetic or optogenetic suppression of mPFC→pPVT activity in adulthood was sufficient to induce sociability deficits without affecting anxiety-related behaviors or preference toward rewarding food.

Adolescent frontal top-down neurons receive heightened local drive to establish adult attentional behavior in mice.

Frontal top-down cortical neurons projecting to sensory cortical regions are well-positioned to integrate long-range inputs with local circuitry in frontal cortex to implement top-down attentional control of sensory regions. How adolescence contributes to the maturation of top-down neurons and associated local/long-range input balance, and the establishment of attentional control is poorly understood. Here we combine projection-specific electrophysiological and rabies-mediated input mapping in mice to uncover adolescence as a developmental stage when frontal top-down neurons projecting from the anterior cingulate to visual cortex are highly functionally integrated into local excitatory circuitry and have heightened activity compared to adulthood.

Prefrontal parvalbumin interneurons require juvenile social experience to establish adult social behavior.

Social isolation during the juvenile critical window is detrimental to proper functioning of the prefrontal cortex (PFC) and establishment of appropriate adult social behaviors. However, the specific circuits that undergo social experience-dependent maturation to regulate social behavior are poorly understood. We identify a specific activation pattern of parvalbumin-positive interneurons (PVIs) in dorsal-medial PFC (dmPFC) prior to an active bout, or a bout initiated by the focal mouse, but not during a passive bout when mice are explored by a stimulus mouse.

The use of laser capture microdissection to identify specific pathways and mechanisms involved in impulsive choice in rats.

Background: Microinjections, lesions, viral-mediated gene transfer, or designer receptors exclusively activated by designer drugs (DREADDs) can identify brain signaling pathways and their pharmacology in research animals. Genetically modified animals are used for more precise assessment of neural circuits. However, only a few of the gene-based pathway modifications are available for use in outbred rat strains.

Juvenile exposure to methylphenidate and guanfacine in rats: effects on early delay discounting and later cocaine-taking behavior.

Rationale: Both methylphenidate (MPH), a catecholamine reuptake blocker, and guanfacine, an alpha2A agonist, are used to treat attention-deficit hyperactivity disorder (ADHD). Childhood impulsivity, including delay discounting, is associated with increased substance use during adolescence. These effects can be mitigated by juvenile exposure to MPH, but less is known about the long-term effects of developmental exposure to guanfacine in males and females.

Anhedonic behavior and γ-amino butyric acid during a sensitive period in female rats exposed to early adversity.

Early life adversity increases depressive behavior that emerges during adolescence. Sensitive periods have been associated with fewer GABAergic interneurons, especially parvalbumin (PV), brain derived growth factor, and its receptor, TrkB. Here, maternal separation (MS) and social isolation (ISO) were used to establish a sensitive period for anhedonic depression using the learned helplessness (LH) paradigm.

Sex differences in the ontogeny of CRF receptors during adolescent development in the dorsal raphe nucleus and ventral tegmental area.

Interactions between corticotropin-releasing factor (CRF) and monoaminergic systems originating from the dorsal raphe nucleus (DR) and ventral tegmental area (VTA) have been implicated in the etiology and pathophysiology of several stress-related neuropsychiatric disorders such as depression and substance abuse. Sub-regions within the DR and VTA give rise to specific projections that have unique roles in limbic- and reward-related behaviors. Given that these disorders typically emerge during adolescence, it is surprising that few studies have examined the age-, sex-, and region-dependent expression of CRF receptors throughout multiple stages of adolescence in these stress-relevant circuits.

Developmental emergence of an obsessive-compulsive phenotype and binge behavior in rats.

Rationale: Obsessive-compulsive disorder (OCD) gradually emerges and reaches clinical significance during early adulthood. Whether a predisposition for OCD manifests as binge eating disorder earlier during adolescence is proposed.

Objectives: To further characterize how OCD-like behaviors increase across maturation and to determine whether an OCD-like predisposition increases the likelihood of binge eating during adolescence.

Dissociation of μ-opioid receptor and CRF-R1 antagonist effects on escalated ethanol consumption and mPFC serotonin in C57BL/6J mice.

Both the opioid antagonist naltrexone and corticotropin-releasing factor type-1 receptor (CRF-R1) antagonists have been investigated for the treatment of alcoholism. The current study examines the combination of naltrexone and CP154526 to reduce intermittent access ethanol drinking [intermittent access to alcohol (IAA)] in C57BL/6J male mice, and if these compounds reduce drinking via serotonergic mechanisms in the dorsal raphe nucleus (DRN). Systemic injections and chronic intracerebroventricular infusions of naltrexone, CP154526 or CP376395 transiently decreased IAA drinking.

Social stress and escalated drug self-administration in mice I. Alcohol and corticosterone.

Rationale: Stress experiences have been shown to be a risk factor for alcohol abuse in humans; however, a reliable mouse model using episodic social stress has yet to be developed.

Objectives: The current studies investigated the effects of mild and moderate social defeat protocols on plasma corticosterone, voluntary alcohol drinking, and motivation to drink alcohol.

Methods: Outbred Carworth Farms Webster (CFW) mice were socially defeated for 10 days during which the intruder mouse underwent mild (15 bites: mean = 1.