Optogenetic stimulation of corticostriatal circuits improves behavioral flexibility in mice with prenatal alcohol exposure.

Fetal alcohol spectrum disorder (FASD) is the most common preventable form of developmental and neurobehavioral disability. Animal models have demonstrated that even low to moderate prenatal alcohol exposure (PAE) is sufficient to impair behavioral flexibility in multiple domains. Previously, utilizing a moderate limited access drinking in the dark paradigm, we have shown that PAE 1) impairs touchscreen pairwise visual reversal in male adult offspring 2) leads to small but significant decreases in orbitofrontal (OFC) firing rates 3) significantly increases dorsal striatum (dS) activity and 4) aberrantly sustains OFC-dS synchrony across early reversal.

Short-active gestational photoperiod reduces effortful choice behavior in mice, partial normalization by d-amphetamine.

Rationale: Seasonal birth patterns consistently implicate winter gestation as a risk factor for several psychiatric conditions. We recently demonstrated that short-active (SA; 19:5 light:dark)-i.e.

iTat transgenic mice exhibit hyper-locomotion in the behavioral pattern monitor after chronic exposure to methamphetamine but are unaffected by Tat expression.

Although antiretroviral therapy (ART) has increased the quality of life and lifespan in people living with HIV (PWH), millions continue to suffer from the neurobehavioral effects of the virus. Additionally, the abuse of illicit drugs (methamphetamine in particular) is significantly higher in PWH compared to the general population, which may further impact their neurological functions. The HIV regulatory protein, Tat, has been implicated in the neurobehavioral impacts of HIV and is purported to inhibit dopamine transporter (DAT) function in a way similar to methamphetamine.

Chronic methamphetamine exposure exerts few effects on the iTat mouse model of HIV, but blocks Tat expression-induced slowed reward retrieval.

Human immunodeficiency virus (HIV) continues to infect millions worldwide, negatively impacting neurobehavioral function. Further understanding of the combined effects of HIV and methamphetamine use is crucial, as methamphetamine use is prevalent in people with HIV. The HIV-associated protein Tat may contribute to cognitive dysfunction, modeled preclinically in mice using doxycycline (DOX)-inducible Tat expression (iTat).

Preclinical Evaluation of Attention and Impulsivity Relevant to Determining ADHD Mechanisms and Treatments.

People with Attention-Deficit Hyperactivity Disorder (ADHD) exhibit inattention, hyperactivity, and/or impulsivity. Symptoms of ADHD emerge in childhood and can continue throughout adulthood. Clinical assessments to diagnose ADHD can include administration of continuous performance tests (CPTs).

Impaired cognitive flexibility following NMDAR-GluN2B deletion is associated with altered orbitofrontal-striatal function.

A common feature across neuropsychiatric disorders is inability to discontinue an action or thought once it has become detrimental. Reversal learning, a hallmark of executive control, requires plasticity within cortical, striatal and limbic circuits and is highly sensitive to disruption of N-methyl-d-aspartate receptor (NMDAR) function. In particular, selective deletion or antagonism of GluN2B containing NMDARs in cortical regions including the orbitofrontal cortex (OFC), promotes maladaptive perseveration.

Chronic antipsychotic treatment exerts limited effects on the mania-like behavior of dopamine transporter knockdown mice.

Background: Bipolar disorder is a life-threatening disorder linked to dopamine transporter (DAT) polymorphisms, with reduced DAT levels seen in positron emission tomography and postmortem brains.

Aims: The purpose of this study was to examine the effects of approved antipsychotics on DAT dysfunction-mediated mania behavior in mice.

Methods: DAT knockdown mice received either D-family receptor antagonist risperidone or asenapine and mania-related behaviors were assessed in the clinically-relevant behavioral pattern monitor to assess spontaneous exploration.

Moderate Prenatal Alcohol Exposure Impairs Visual-Spatial Discrimination in a Sex-Specific Manner: Effects of Testing Order and Difficulty on Learning Performance.

Background: Exposure to high levels of alcohol during development leads to alterations in neurogenesis and deficits in hippocampal-dependent learning. Evidence suggests that even more moderate alcohol consumption during pregnancy can have negative impacts on the cognitive function of offspring. Methods for assessing impairments differ greatly across species, complicating translation of preclinical findings into potential therapeutics.

Moderate prenatal alcohol exposure alters the number and function of GABAergic interneurons in the murine orbitofrontal cortex.

Exposure to alcohol during development produces Fetal Alcohol Spectrum Disorders (FASD), characterized by a wide range of effects that include deficits in multiple cognitive domains. Early identification and treatment of individuals with FASD remain a challenge because neurobehavioral alterations do not become a significant problem until late childhood and early adolescence. Understanding the mechanisms underlying low and moderate prenatal alcohol exposure (PAE) effects on behavior and cognition is essential for improved diagnosis and treatment.

Impaired cognitive flexibility following NMDAR-GluN2B deletion is associated with altered orbitofrontal-striatal function.

A common feature across neuropsychiatric disorders is inability to discontinue an action or thought once it has become detrimental. Reversal learning, a hallmark of executive control, requires plasticity within cortical, striatal and limbic circuits and is highly sensitive to disruption of N-methyl--aspartate receptor (NMDAR) function. In particular, selective deletion or antagonism of GluN2B containing NMDARs in cortical regions including the orbitofrontal cortex (OFC), promotes maladaptive perseveration.

Cortico-hippocampal GluN2B is essential for efficient visual-spatial discrimination learning in a touchscreen paradigm.

Discrimination of similar spatial locations, an important feature of episodic memory, has traditionally been measured via delayed nonmatching-to-location tasks. Recently, we and others have demonstrated that touchscreen-based Trial Unique Nonmatching-to-Location (TUNL) tasks are sensitive to lesions of the dorsal hippocampus in the mouse. Previously we have shown that loss of the GluN2B subunit of the N-methyl-D-aspartate (NMDA) receptor in the dorsal CA1 and throughout the cortex impairs hippocampal-dependent water maze and fear conditioning paradigms.

Overexpression of neuronal RNA-binding protein HuD increases reward induced reinstatement of an instrumental response.

The neuronal RNA-binding protein HuD is involved in synaptic plasticity and the molecular mechanisms of learning and memory. Previously, we have shown that HuD is upregulated after both spatial and addiction-associated forms of learning, such as conditioned place preference. However, what role HuD plays in non-drug dependent learning and memory is not fully understood.

Amphetamine improves mouse and human attention in the 5-choice continuous performance test.

Non-medical use of prescription stimulants amongst college students is common, with claims of cognitive and academic benefits. The mechanism, magnitude, and pervasiveness of the cognitive enhancing effects of stimulants in healthy adults remain poorly understood however. The present study determined the effects of dextroamphetamine (D-amp) on the 5-choice continuous performance test (5C-CPT) of attention in healthy young adult humans and mice.