Representation of odorants by receptor neuron input to the mouse olfactory bulb

Author Posting. © The Author(s), 2001. This is the author's version of the work. It is posted here by permission of Elsevier B. V. for personal use, not for redistribution. The definitive version was published in Neuron 32 (2001): 723-735, doi:10.1016/S0896-6273(01)00506-2.To visualize odorant representations by receptor neuron input to the mouse olfactory bulb, we loaded receptor neurons with calcium-sensitive dye and imaged odorant-evoked responses from their axon terminals. Fluorescence increases reflected activation of receptor neuron populations converging onto individual glomeruli. We report several findings. First, five glomeruli were identifiable across animals based on their location and odorant responsiveness; all five showed complex response specificities. Second, maps of input were chemotopically organized at near-threshold concentrations but, at moderate concentrations, involved many widely distributed glomeruli. Third, the dynamic range of input to a glomerulus was greater than that reported for individual receptor neurons. Finally, odorant activation slopes could differ across glomeruli, and for different odorants activating the same glomerulus. These results imply a high degree of complexity in odorant representations at the level of olfactory bulb input.This work was supported by NIH NS08437-DC05259 and DC00378-03

Oxidative stress-driven parvalbumin interneuron impairment as a common mechanism in models of schizophrenia.

Parvalbumin inhibitory interneurons (PVIs) are crucial for maintaining proper excitatory/inhibitory balance and high-frequency neuronal synchronization. Their activity supports critical developmental trajectories, sensory and cognitive processing, and social behavior. Despite heterogeneity in the etiology across schizophrenia and autism spectrum disorder, PVI circuits are altered in these psychiatric disorders. Identifying mechanism(s) underlying PVI deficits is essential to establish treatments targeting in particular cognition. On the basis of published and new data, we propose oxidative stress as a common pathological mechanism leading to PVI impairment in schizophrenia and some forms of autism. A series of animal models carrying genetic and/or environmental risks relevant to diverse etiological aspects of these disorders show PVI deficits to be all accompanied by oxidative stress in the anterior cingulate cortex. Specifically, oxidative stress is negatively correlated with the integrity of PVIs and the extracellular perineuronal net enwrapping these interneurons. Oxidative stress may result from dysregulation of systems typically affected in schizophrenia, including glutamatergic, dopaminergic, immune and antioxidant signaling. As convergent end point, redox dysregulation has successfully been targeted to protect PVIs with antioxidants/redox regulators across several animal models. This opens up new perspectives for the use of antioxidant treatments to be applied to at-risk individuals, in close temporal proximity to environmental impacts known to induce oxidative stress

Interactive histogenesis of axonal strata and proliferative zones in the human fetal cerebral wall

Development of the cerebral wall is characterized by partially overlapping histogenetic events. However, little is known with regards to when, where, and how growing axonal pathways interact with progenitor cell lineages in the proliferative zones of the human fetal cerebrum. We analyzed the developmental continuity and spatial distribution of the axonal sagittal strata (SS) and their relationship with proliferative zones in a series of human brains (8-40 post-conceptional weeks; PCW) by comparing histological, histochemical, and immunocytochemical data with magnetic resonance imaging (MRI). Between 8.5 and 11 PCW, thalamocortical fibers from the intermediate zone (IZ) were initially dispersed throughout the subventricular zone (SVZ), while sizeable axonal "invasion" occurred between 12.5 and 15 PCW followed by callosal fibers which "delaminated" the ventricular zone-inner SVZ from the outer SVZ (OSVZ). During midgestation, the SS extensively invaded the OSVZ, separating cell bands, and a new multilaminar axonal-cellular compartment (MACC) was formed. Preterm period reveals increased complexity of the MACC in terms of glial architecture and the thinning of proliferative bands. The addition of associative fibers and the formation of the centrum semiovale separated the SS from the subplate. In vivo MRI of the occipital SS indicates a "triplet" structure of alternating hypointense and hyperintense bands. Our results highlighted the developmental continuity of sagittally oriented "corridors" of projection, commissural and associative fibers, and histogenetic interaction with progenitors, neurons, and glia. Histogenetical changes in the MACC, and consequently, delineation of the SS on MRI, may serve as a relevant indicator of white matter microstructural integrity in the developing brain

Response to depression treatment in the Aging Brain Care Medical Home model

Michael A LaMantia,1–4 Anthony J Perkins,5,6 Sujuan Gao,2,7 Mary G Austrom,8,9 Cathy A Alder,10 Dustin D French,11,12 Debra K Litzelman,2,3,13 Ann H Cottingham,3 Malaz A Boustani1–3,5 1Indiana University Center for Aging Research, 2Regenstrief Institute, Inc., 3Department of Medicine, Indiana University School of Medicine, Indianapolis, IN, 4Department of Medicine, University of Vermont College of Medicine, Burlington, VT, 5Indiana University Center for Health Innovation and Implementation Science, 6Indiana Clinical and Translational Sciences Institute, 7Department of Biostatistics, Indiana University School of Medicine, 8Department of Psychiatry, Indiana University School of Medicine, 9Indiana University Alzheimer’s Disease Center, 10Eskenazi Health, Indianapolis, IN, 11Department of Ophthalmology, Feinberg School of Medicine, Northwestern University, 12Veterans Affairs Health Services Research and Development Service, Chicago, IL, 13Indiana University Center for Health Services and Outcomes Research, Indianapolis, IN, USA Objective: To evaluate the effect of the Aging Brain Care (ABC) Medical Home program’s depression module on patients’ depression severity measurement over time.Design: Retrospective chart review.Setting: Public hospital system.Participants: Patients enrolled in the ABC Medical Home program between October 1, 2012 and March 31, 2014.Methods: The response of 773 enrolled patients who had multiple patient health questionnaire-9 (PHQ-9) scores recorded in the ABC Medical Home program’s depression care protocol was evaluated. Repeatedly measured PHQ-9 change scores were the dependent variables in the mixed effects models, and demographic and comorbid medical conditions were tested as potential independent variables while including random effects for time and intercept.Results: Among those patients with baseline PHQ-9 scores >10, there was a significant decrease in PHQ-9 scores over time (P<0.001); however, the effect differed by gender (P=0.015). On average, women’s scores (4.5 point drop at 1 month) improved faster than men’s scores (1 point drop at 1 month). Moreover, both men and women had a predicted drop of 7 points (>50% decline from baseline) on the PHQ-9 at 6 months. Conclusion: These analyses demonstrate evidence for the sustained effectiveness of the ABC Medical Home program at inducing depression remission outcomes while employing clinical staff who required less formal training than earlier clinical trials. Keywords: geriatrics, care coordination, Medicar

The recognition and management of sepsis in urgent care out of hours setting

As the majority of sepsis cases occur in the community, Justine Dexter and Gerri Mortimore provide an overview of the assessment, diagnosis and management of the condition for those working in out of hours settings. Sepsis is a life-threatening and common condition prompted by a microbial infection. Sepsis is responsible for the death of more people than prostate, bowel or breast cancer collectively, and it causes the second highest mortality rates after cardiovascular disease. The majority of sepsis cases occur in the community, with 30% developing while the patient is in hospital. In many instances, sepsis is avoidable and treatable. The aetiology of sepsis is not always known, making diagnosis difficult, with only 50% of cases having a confirmed pathogenic organism. The signs and symptoms most obviously connected with sepsis are confusion or unusual behaviour, hypotension and increased respiratory rate. However, some patients have non-specific symptoms, and just complain of feeling extremely unwell. Any patients who have these signs or symptoms should be assessed for the possibility of sepsis, regardless of whether pyrexia is present. To aid in detection and decision making about sepsis, the use of screening tools have been advocated to shorten the period prior to the administration of antibiotics. Children characteristically compensate physiologically for a considerable time and then deteriorate quickly; therefore, a crucial focus is to spot a sick child rapidly. Many urgent care out of hours (UCOOH) services are nurse-led. Therefore, it often falls on advanced nurse practitioners (ANPs) to educate healthcare assistants to spot the sick person, especially as they are usually the first person the patient sees. Leadership plays a key role for ANPs in UCOOH by helping to progress the pathway for patients to ensure the sickest are prioritised.N/