Repeated toluene inhalation in male and female adolescent rats induces persistent drug preference and impairs cognitive and social behavior.

Rationale: Adolescent inhalant use is an understudied and undertreated disorder, particularly in females. Chronic exposure to inhalants, like toluene, can have long-lasting effects on behavior. However, most animal studies lack the incorporation of both sexes and do not focus on the abstinence period.

Mentoring to propagate racial inclusivity in neuroscience.

Mentoring the next generation of neuroscientists from historically excluded backgrounds brings several challenges. Successful mentor-mentee relationships are critical for addressing these challenges. Rodriguez-Romaguera and Quirk reflect on lessons learned from their cross-racial mentor-mentee relationship that could apply to many mentors.

Specific Patterns of Endogenous Functional Connectivity Are Associated With Harm Avoidance in Obsessive-Compulsive Disorder.

Background: Individuals with obsessive-compulsive disorder (OCD) show persistent avoidance behaviors, often in the absence of actual threat. Quality-of-life costs and heterogeneity support the need for novel brain-behavior intervention targets. Informed by mechanistic and anatomical studies of persistent avoidance in rodents and nonhuman primates, our goal was to test whether connections within a hypothesized persistent avoidance-related network predicted OCD-related harm avoidance (HA), a trait measure of persistent avoidance.

A Novel Insular/Orbital-Prelimbic Circuit That Prevents Persistent Avoidance in a Rodent Model of Compulsive Behavior.

Background: A common symptom of obsessive-compulsive disorder is the persistent avoidance of cues incorrectly associated with negative outcomes. This maladaptation becomes increasingly evident as subjects fail to respond to extinction-based treatments such as exposure-with-response prevention therapy. While previous studies have highlighted the role of the insular-orbital cortex in fine-tuning avoidance-based decisions, little is known about the projections from this area that might modulate compulsive-like avoidance.

Time-Dependent Recruitment of Prelimbic Prefrontal Circuits for Retrieval of Fear Memory.

The long-lasting nature of fear memories is essential for survival, but the neural circuitry for retrieval of these associations changes with the passage of time. We previously reported a time-dependent shift from prefrontal-amygdalar circuits to prefrontal-thalamic circuits for the retrieval of auditory fear conditioning. However, little is known about the time-dependent changes in the originating site, the prefrontal cortex.

Characterizing Different Strategies for Resolving Approach-Avoidance Conflict.

The ability of animals to maximize benefits and minimize costs during approach-avoidance conflicts is an important evolutionary tool, but little is known about the emergence of specific strategies for conflict resolution. Accordingly, we developed a simple approach-avoidance conflict task in rats that pits the motivation to press a lever for sucrose against the motivation to step onto a distant platform to avoid a footshock delivered at the end of a 30 s tone (sucrose is available only during the tone). Rats received conflict training for 16 days to give them a chance to optimize their strategy by learning to properly time the expression of both behaviors across the tone.

Building a Diverse Workforce and Thinkforce to Reduce Health Disparities.

The Research Centers in Minority Institutions (RCMI) Program was congressionally mandated in 1985 to build research capacity at institutions that currently and historically recruit, train, and award doctorate degrees in the health professions and health-related sciences, primarily to individuals from underrepresented and minority populations. RCMI grantees share similar infrastructure needs and institutional goals. Of particular importance is the professional development of multidisciplinary teams of academic and community scholars (the "workforce") and the harnessing of the heterogeneity of thought (the "thinkforce") to reduce health disparities.

Neural mechanisms of persistent avoidance in OCD: A novel avoidance devaluation study.

Obsessive-Compulsive Disorder (OCD) is characterized by repetitive avoidance behavior which is distressing and associated with marked impairment of everyday life. Recently, paradigms have been designed to explore the hypothesis that avoidance behavior in OCD is consistent with a formal conception of habit. Such studies have involved a devaluation paradigm, in which the value of a previously rewarded cue is altered so that avoidance is no longer necessary.

Prolonged avoidance training exacerbates OCD-like behaviors in a rodent model.

Obsessive-compulsive disorder (OCD) is characterized by compulsive behaviors that often resemble avoidance of perceived danger. OCD can be treated with exposure-with-response prevention (ERP) therapy in which patients are exposed to triggers but are encouraged to refrain from compulsions, to extinguish compulsive responses. The compulsions of OCD are strengthened by many repeated exposures to triggers, but little is known about the effects of extended repetition of avoidance behaviors on extinction.

Functional disruption in prefrontal-striatal network in obsessive-compulsive disorder.

Obsessive-compulsive disorder (OCD) is characterized by intrusive thoughts and repetitive, compulsive behaviors. While a cortico-striatal-limbic network has been implicated in the pathophysiology of OCD, the neural correlates of this network in OCD are not well understood. In this study, we examined resting state functional connectivity among regions within the cortico-striatal-limbic OCD neural network, including the rostral anterior cingulate cortex, dorsolateral prefrontal cortex, ventrolateral prefrontal cortex, orbitofrontal cortex, ventromedial prefrontal cortex, amygdala, thalamus and caudate, in 44 OCD and 43 healthy participants.

The Storytelling Brain: How Neuroscience Stories Help Bridge the Gap between Research and Society.

Active communication between researchers and society is necessary for the scientific community's involvement in developing science-based policies. This need is recognized by governmental and funding agencies that compel scientists to increase their public engagement and disseminate research findings in an accessible fashion. Storytelling techniques can help convey science by engaging people's imagination and emotions.

A NeuroD1 AAV-Based Gene Therapy for Functional Brain Repair after Ischemic Injury through In Vivo Astrocyte-to-Neuron Conversion.

Adult mammalian brains have largely lost neuroregeneration capability except for a few niches. Previous studies have converted glial cells into neurons, but the total number of neurons generated is limited and the therapeutic potential is unclear. Here, we demonstrate that NeuroD1-mediated in situ astrocyte-to-neuron conversion can regenerate a large number of functional new neurons after ischemic injury.

The study of active avoidance: A platform for discussion.

Traditional active avoidance tasks have advanced the field of aversive learning and memory for decades and are useful for studying simple avoidance responses in isolation; however, these tasks have limited clinical relevance because they do not model several key features of clinical avoidance. In contrast, platform-mediated avoidance (PMA) more closely resembles clinical avoidance because the response i) is associated with an unambiguous safe location, ii) is not associated with an artificial termination of the warning signal, and iii) is associated with a decision-based appetitive cost. Recent findings on the neuronal circuits of PMA have confirmed that amygdala-striatal circuits are essential for avoidance.

Neuroscience Research and Mentoring in Puerto Rico: What Succeeds in This Environment?

Twenty years ago, I arrived in Puerto Rico from New York City to establish a neuroscience laboratory and research program on extinction of conditioned fear. The lab's first research paper appeared in the (Quirk et al., 2000) and has been cited >900 times.

Prefrontal circuits signaling active avoidance retrieval and extinction.

Objective: Neurons in PL and IL project densely to two areas implicated in active avoidance: the basolateral amygdala (BLA) and the ventral striatum (VS). We therefore combined c-Fos immunohistochemistry with retrograde tracers to characterize signaling in platform-mediated active avoidance.

Methods: Male rats  were infused with retrograde tracers (CTB, FB) into basolateral amygdala and ventral striatum and conditioned to avoid tone-signaled footshocks by stepping onto a nearby platform.

Alteration of BDNF in the medial prefrontal cortex and the ventral hippocampus impairs extinction of avoidance.

Brain-derived neurotrophic factor (BDNF) is critical for establishing activity-related neural plasticity. There is increasing interest in the mechanisms of active avoidance and its extinction, but little is known about the role of BDNF in these processes. Using the platform-mediated avoidance task combined with local infusions of an antibody against BDNF, we show that blocking BDNF in either prelimbic (PL) or infralimbic (IL) medial prefrontal cortex during extinction training impairs subsequent recall of extinction of avoidance, differing from extinction of conditioned freezing.

Thalamic Regulation of Sucrose Seeking during Unexpected Reward Omission.

The paraventricular nucleus of the thalamus (PVT) is thought to regulate behavioral responses under emotionally arousing conditions. Reward-associated cues activate PVT neurons; however, the specific PVT efferents regulating reward seeking remain elusive. Using a cued sucrose-seeking task, we manipulated PVT activity under two emotionally distinct conditions: (1) when reward was available during the cue as expected or (2) when reward was unexpectedly omitted during the cue.

Less fear, more diversity.

Fear is an instinctual response that's adaptive and critical for survival when it is short-lived but can lead to anxiety disorders when chronic. Studying how the brain controls our fears helps us understand the mechanisms required to recover from traumatic experiences and what goes wrong when we don't. Research in rodents has identified neural circuits and molecular mechanisms regulating fear expression.