REGULATION OF THE INHIBITORY DRIVE IN THE OLFACTORY BULB

Animals are exposed to a variety of odor cues that serve as environmental guides for their exploratory and social behaviors. Two distinct but complementing pathways process chemosensory cues: the Main and the Accessory olfactory System (AOS). Sensory neurons send their axons to the olfactory bulb (OB), specifically to the main and the accessory olfactory bulb (MOB and AOB, respectively) where they synapse onto principal neurons, the mitral (MCs). The OB is the only relay center between sensory neurons and cortical and limbic structures and therefore important aspects of odor processing occur in this region. Specifically, a distinctive mechanism used for olfactory processing is a strict regulation of MCs output by inhibitory neurons called granule cells (GCs). Importantely, inhibition of MCs is a dynamic process; it is regulated by the constant addition of new GCs to the OB circuit throughout life, in a process known as adult neurogenesis. Little is known, however, about the contribution of adult born neurons to the processing of olfactory cues, known as pheromones. Detection of pheromones by the AOS is critical for proper display of social behaviors such as hierarchical dominance and mate recognition. Here, we studied how the integration of new-born neurons could be regulated. We found that the arrival of new neurons into the adult AOB increases after animals are exposed to aggression and mate cues, suggesting that these newly arrived neurons can add important plasticity to the AOB circuitry and modify olfactory processing under different behavioral contexts. In addition, GCs mediated inhibition in the OB is precisely controlled by an extensive centrifugal innervation. For example, cortical feedback projections and neuromodulatory afferents originating in the midbrain and basal forebrain excite GC, inhibiting MCs' and decreasing their output. Regulation of of GCs by inhibition has also been reported, however, the source of this inhibition and its relevance to olfactory processing is not known. Here we characterized inhibitory inputs onto GCs and show that GCs receive extensive inhibition from GABAergic neurons in the HDB/MCPO and from neighboring GCs. Moreover, we show, for the first time, that inhibition onto GCs is required for proper olfactory discrimination

ALPY PLUS - Adaptive Model Oriented to Pathway Planning in Virtual Learning System

This paper presents an adaptive model called ALPY PLUS to enrich the dynamic planning of learning resources with user characteristics and those of her/his context, in order to provide a personalized course in a virtual environment. We describe the proposed architecture, the visual prototype, together with the main components, actions and services required by the adaptive model. © 2022, Springer Nature Switzerland AG

Knowledge of Medicaid Expansion to Recent and Undocumented Immigrants Among Oregon Mexican-origin Latinos: (Work in Progress)

Background Recent and undocumented immigrants are explicitly excluded from federal Medicaid and state insurance exchanges. The first phase of Healthier Oregon was implemented in July 2022 and expanded Medicaid (OHP) benefits to undocumented immigrants ages 19-25 or 55 and older. The second phase was implemented in July 2023 and extended benefits to everyone regardless of age. We assessed understanding of Healthier Oregon among Mexican-origin Latinos. We hypothesize that many potentially eligible people may not know about the program, if they qualify, or how to apply. Methods This is a cross-sectional study in collaboration with the General Consulate of Mexico. Our team has developed a 19-item cross-sectional survey. This survey includes socio-demographic items and knowledge about Healthier Oregon. Study participants are individuals who are 18 and older, reside in Oregon, and self-identify as Latino/as. We will use descriptive and multivariable statistics to describe our sample, awareness of the Healthier Oregon program, experience enrolling, and factors associated with awareness of Healthier Oregon. Results We have recruited 234 out of 500 planned participants to date. Analyses are ongoing and we will have preliminary data for the SPH conference The study results will be disseminated with the Consulate of Mexico, other local partners, and in a scientific publication. Public Health Significance Recent and undocumented immigrants are explicitly excluded from Medicaid. Oregon has passed legislation to fill this gap. Understanding awareness of the program will provide insight into ways to improve outreach and communication and improve enrollment by eligible individuals

Synthetically induced Arabidopsis thaliana autotetraploids provide insights into the analysis of meiotic mutants with altered crossover frequency

Mutations affecting crossover (CO) frequency and distribution lead to the presence of univalents during meiosis, giving rise to aneuploid gametes and sterility. These mutations may have a different effect after chromosome doubling. The combination of altered ploidy and mutations could be potentially useful to gain new insights into the mechanisms and regulation of meiotic recombination; however, studies using autopolyploid meiotic mutants are scarce. Here, we have analyzed the cytogenetic consequences in colchicine-induced autotetraploids (colchiploids) from different Arabidopsis mutants with an altered CO frequency. We have found that there are three types of mutants: mutants in which chiasma frequency is doubled after chromosome duplication (zip4, mus81), as in the control; mutants in which polyploidy leads to a higher-than-expected increase in chiasma frequency (asy1, mer3, hei10, and mlh3); and mutants in which the rise in chiasma frequency produced by the presence of two extrachromosomal sets is less than doubled (msh5, fancm). In addition, the proportion of class I/class II COs varies after chromosome duplication in the control. The results obtained reveal the potential of colchiploid meiotic mutants for better understanding of the function of key proteins during plant meiosis. This is especially relevant considering that most crops are polyploids.Depto. de Genética, Fisiología y MicrobiologíaFac. de Ciencias BiológicasTRUEpu

Structural and Functional Abnormalities in the Olfactory System of Fragile X Syndrome Models

Fragile X Syndrome (FXS) is the most common inherited form of intellectual disability. It is produced by mutation of the Fmr1 gene that encodes for the Fragile Mental Retardation Protein (FMRP), an important RNA-binding protein that regulates the expression of multiple proteins located in neuronal synapses. Individuals with FXS exhibit abnormal sensory information processing frequently leading to hypersensitivity across sensory modalities and consequently a wide array of behavioral symptoms. Insects and mammals engage primarily their sense of smell to create proper representations of the external world and guide adequate decision-making processes. This feature in combination with the exquisitely organized neuronal circuits found throughout the olfactory system (OS) and the wide expression of FMRP in brain regions that process olfactory information makes it an ideal model to study sensory alterations in FXS models. In the last decade several groups have taken advantage of these features and have used the OS of fruit fly and rodents to understand neuronal alteration giving rise to sensory perception issues. In this review article, we will discuss molecular, morphological and physiological aspects of the olfactory information processing in FXS models. We will highlight the decreased inhibitory/excitatory synaptic balance and the diminished synaptic plasticity found in this system resulting in behavioral alteration of individuals in the presence of odorant stimuli

A stressz rendszer szerepe az ópiát függőség kialakulásában: idegi, sejtszintű és molekuláris mechanizmusok = Involvement of brain stress system in opiate addiction: neuronal substrates, cellular and molecular mechanisms

1. A morfium függőség és megvonás aktiválja a neuroendokrin és az agyi stresszrendszert. 2. A hipotalamusz paravntrikuláris magjában illetve az ""extended"" amigdalában expresszálódó kortikotropin-releasing hormon (CRH) különböző módon szabályozza a morfium addikciót és megvonást kísérő hormonális, élettani és magatartási (érzelmi) reakciókat. 3. Sejtszinten a cAMP-reponse element binding protein (CREB) és a hozzá csatlakozó ko-regulátor fehérjék, mint pl a foszforilált TORC fontos szerepet játszanak a drogmegvonás kapcsán aktiválódó CRH gén szabályozásában mind a hipotalamuszban, mind az ""extended"" amigdalában. 4. A hipotalamikus és extrahipotalamikus területeket beidegző felszálló noradrenerg és orexinerg pályák különböző mechanizmussal vesznek részt a drogfüggőséggel és a drogmegvonással járó megvonási tünetek kialakításában. 5. A morfium függőséggel és a naloxonnal történő morfium megvonás okozta anyagcsere változások a hipotalamuszban eltérő módon befolyásolják a stresszel és a metabolikus szabályozássaél kapcsolatos neuropaptid gének expresszióját. | 1. Morphine dependence and naloxone-precipitated morphine withdrawal results in activation of the neuroendocrine and brain stress systems in the rat brain. 2. Corticotropin-releasing hormone expressed in the hypophyseotropic cells of the hypothalamus as well as in the extended amygdala plays a differential role in the development of hormonal, physiological, emotional and behavioral changes in addicted animals. 3. cAMP-response element binding protein (CREB) and its co-activators (such as pTORC) play a critical role in activation of corticotropin-releasing hormone gene expression both in the hypothalamus and in the extended amygdala. 4. Ascending noradrenergic and orexinergic pathways innervating hypothalamic and extrahypothalamic sites differentially regulate the development of hormonal, somatic and psychological symptoms of morphine withdrawal. 5. Metabolic changes associated by drug dependence and withdrawal result in differential changes of metabolic and stress-related neuropeptides in the hypothalamus

Mice Lacking M1 and M3 Muscarinic Acetylcholine Receptors Have Impaired Odor Discrimination and Learning

Partial funding for Open Access provided by the UMD Libraries' Open Access Publishing Fund.The cholinergic system has extensive projections to the olfactory bulb (OB) where it produces a state-dependent regulation of sensory gating. Previous work has shown a prominent role of muscarinic acetylcholine (ACh) receptors (mAChRs) in regulating the excitability of OB neurons, in particular the M1 receptor. Here, we examined the contribution of M1 and M3 mAChR subtypes to olfactory processing using mice with a genetic deletion of these receptors, the M1-/- and the M1/M3-/- knockout (KO) mice. Genetic ablation of the M1 and M3 mAChRs resulted in a significant deficit in odor discrimination of closely related molecules, including stereoisomers. However, the discrimination of dissimilar molecules, social odors (e.g., urine) and novel object recognition was not affected. In addition the KO mice showed impaired learning in an associative odor-learning task, learning to discriminate odors at a slower rate, indicating that both short and long-term memory is disrupted by mAChR dysfunction. Interestingly, the KO mice exhibited decreased olfactory neurogenesis at younger ages, a deficit that was not maintained in older animals. In older animals, the olfactory deficit could be restored by increasing the number of new born neurons integrated into the OB after exposing them to an olfactory enriched environment, suggesting that muscarinic modulation and adult neurogenesis could be two different mechanism used by the olfactory system to improve olfactory processing

Abatacept, Cenicriviroc, or Infliximab for Treatment of Adults Hospitalized With COVID-19 Pneumonia: A Randomized Clinical Trial

IMPORTANCE: Immune dysregulation contributes to poorer outcomes in COVID-19. OBJECTIVE: To investigate whether abatacept, cenicriviroc, or infliximab provides benefit when added to standard care for COVID-19 pneumonia. DESIGN, SETTING, AND PARTICIPANTS: Randomized, double-masked, placebo-controlled clinical trial using a master protocol to investigate immunomodulators added to standard care for treatment of participants hospitalized with COVID-19 pneumonia. The results of 3 substudies are reported from 95 hospitals at 85 clinical research sites in the US and Latin America. Hospitalized patients 18 years or older with confirmed SARS-CoV-2 infection within 14 days and evidence of pulmonary involvement underwent randomization between October 2020 and December 2021. INTERVENTIONS: Single infusion of abatacept (10 mg/kg; maximum dose, 1000 mg) or infliximab (5 mg/kg) or a 28-day oral course of cenicriviroc (300-mg loading dose followed by 150 mg twice per day). MAIN OUTCOMES AND MEASURES: The primary outcome was time to recovery by day 28 evaluated using an 8-point ordinal scale (higher scores indicate better health). Recovery was defined as the first day the participant scored at least 6 on the ordinal scale. RESULTS: Of the 1971 participants randomized across the 3 substudies, the mean (SD) age was 54.8 (14.6) years and 1218 (61.8%) were men. The primary end point of time to recovery from COVID-19 pneumonia was not significantly different for abatacept (recovery rate ratio [RRR], 1.12 [95% CI, 0.98-1.28]; P = .09), cenicriviroc (RRR, 1.01 [95% CI, 0.86-1.18]; P = .94), or infliximab (RRR, 1.12 [95% CI, 0.99-1.28]; P = .08) compared with placebo. All-cause 28-day mortality was 11.0% for abatacept vs 15.1% for placebo (odds ratio [OR], 0.62 [95% CI, 0.41-0.94]), 13.8% for cenicriviroc vs 11.9% for placebo (OR, 1.18 [95% CI 0.72-1.94]), and 10.1% for infliximab vs 14.5% for placebo (OR, 0.59 [95% CI, 0.39-0.90]). Safety outcomes were comparable between active treatment and placebo, including secondary infections, in all 3 substudies. CONCLUSIONS AND RELEVANCE: Time to recovery from COVID-19 pneumonia among hospitalized participants was not significantly different for abatacept, cenicriviroc, or infliximab vs placebo. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT04593940