Prefrontal Interneurons: Populations, Pathways, and Plasticity Supporting Typical and Disordered Cognition in Rodent Models

Prefrontal cortex (PFC) inhibitory microcircuits regulate the gain and timing of pyramidal neuron firing, coordinate neural ensemble interactions, and gate local and long-range neural communication to support adaptive cognition and contextually tuned behavior. Accordingly, perturbations of PFC inhibitory microcircuits are thought to underlie dysregulated cognition and behavior in numerous psychiatric diseases and relevant animal models. This review, based on a Mini-Symposium presented at the 2022 Society for Neuroscience Meeting, highlights recent studies providing novel insights into: (1) discrete medial PFC (mPFC) interneuron populations in the mouse brain; (2) mPFC interneuron connections with, and regulation of, long-range mPFC afferents; and (3) circuit-specific plasticity of mPFC interneurons. The contributions of such populations, pathways, and plasticity to rodent cognition are discussed in the context of stress, reward, motivational conflict, and genetic mutations relevant to psychiatric disease

How to design an art-science program? Self-reported benefits for artists and scientists in the VI4 artist-in-residence program.

While many new programs bridge the arts and sciences, a data-based examination of art-science program design can lead to more efficient programming. The Vanderbilt Institute for Infection, Immunology, and Inflammation Artist-in-Residence program is a virtual program that brings together undergraduate student "artists" and faculty-level "scientists" to generate science-art content. We have recruited over 80 artists and 50 scientists to collaborate in creating visual science communication content. Using self-reported data from both groups, we performed qualitative and quantitative analyses to define sources for negative and positive experiences for artists and scientists. We also identify areas for improvement and key features for in producing a positive experience. We found that artists participants had more positive responses about "learning something new" from the program than scientists. We also found that for both artists and scientists the length of the program and the virtual nature were identified as key features that could be improved. However, the most surprising aspect of our analysis suggests that for both "way of thinking" and "science communication to the public or general audience," were seen as significant beneficial gains for scientists compared to artists. We conclude this analysis with suggestions to enhance the benefits and outcomes of an art-science program and ways to minimize the difficulties, such as communication and collaboration, faced by participants and program designers

Functional partnership between mGlu3 and mGlu5 metabotropic glutamate receptors in the central nervous system

mGlu5 receptors are involved in mechanisms of activity-dependent synaptic plasticity, and are targeted by drugs developed for the treatment of CNS disorders. We report that mGlu3 receptors, which are traditionally linked to the control of neurotransmitter release, support mGlu5 receptor signaling in neurons and largely contribute to the robust mGlu5 receptor-mediated polyphosphoinositide hydrolysis in the early postnatal life. In cortical pyramidal neurons, mGlu3 receptor activation potentiated mGlu5 receptor-mediated somatic Ca2+ mobilization, and mGlu3 receptor-mediated long-term depression in the prefrontal cortex required the endogenous activation of mGlu5 receptors. The interaction between mGlu3 and mGlu5 receptors was also relevant to mechanisms of neuronal toxicity, with mGlu3 receptors shaping the influence of mGlu5 receptors on excitotoxic neuronal death. These findings shed new light into the complex role played by mGlu receptors in physiology and pathology, and suggest reconsideration of some of the current dogmas in the mGlu receptor field

Incidence and Survival of Hospitalized Acute Decompensated Heart Failure in Four US Communities (from the Atherosclerosis Risk in Communities Study)

Most population-based estimates of incident hospitalized heart failure (HF) have not differentiated acute decompensated heart failure (ADHF) from chronic stable HF nor included racially diverse populations. The Atherosclerosis Risk in Communities Study conducted surveillance of hospitalized HF events (age ≥55 years) in 4 US communities. We estimated hospitalized ADHF incidence and survival by race and gender. Potential 2005 to 2009 HF hospitalizations were identified by International Classification of Diseases, Ninth Revision, Clinical Modification, codes; 6,168 records were reviewed to validate ADHF cases. Population estimates were derived from US Census data; 50% of eligible hospitalizations were classified as ADHF, of which 63.6% were incident ADHF and 36.4% were recurrent ADHF. The average incidence of hospitalized ADHF was 11.6 per 1,000 persons, aged ≥55 years, per year, and recurrent hospitalized ADHF was 6.6 per 1,000 persons/yr. Age-adjusted annual ADHF incidence was highest for black men (15.7 per 1,000), followed by black women (13.3 per 1,000), white men (12.3 per 1,000), and white women (9.9 per 1,000). Of incident ADHF events with heart function assessment (89%), 53% had reduced the ejection fraction (heart failure with reduced ejection fraction [HFrEF]) and 47% had preserved ejection fraction (heart failure with preserved ejection fraction [HFpEF]). Black men had the highest proportion of acute HFrEF events (70%); white women had the highest proportion of acute HFpEF (59%). Age-adjusted 28-day and 1-year case fatality after an incident ADHF was 10.4% and 29.5%, respectively. Survival did not differ by race or gender. In conclusion, ADHF hospitalization and HF type varied by both race and gender, but case fatality rates did not. Further studies are needed to explain why black men are at higher risk of hospitalized ADHF and HFrEF

CYT997: a novel orally active tubulin polymerization inhibitor with potent cytotoxic and vascular disrupting activity in vitro and in vivo

CYT997 is a wholly synthetic compound that possesses highly potent cytotoxic activity in vitro through inhibition of microtubule polymerization. CYT997 blocks the cell cycle at the G-M boundary, and Western blot analysis indicates an increase in phosphorylated Bcl-2, along with increased expression of cyclin B1. Caspase-3 activation is also observed in cells treated with CYT997 along with the generation of poly(ADP-ribose) polymerase. The compound possesses favorable pharmacokinetic properties, is orally bioavailable, and is efficacious per os in a range of in vivo cancer models, including some refractory to paclitaxel treatment. CYT997 exhibits vascular disrupting activity as measured in vitro by effects on the permeability of human umbilical vein endothelial cell monolayers, and in vivo by effects on tumor blood flow. CYT997 possesses a useful combination of pharmacologic and pharmacokinetic properties and has considerable potential as a novel anticancer agent