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The Effect of Mobile Self-monitoring on Self-care Behaviors in Heart Failure and COPD Patients: A Feasibility Study

Fri, 05/20/2016 - 3:30pm

Exacerbations of heart failure (HF) and chronic obstructive lung disease (COPD) are among the most costly illnesses. Patient recognition of changes in symptoms cueing imminent exacerbation is poor. Innovative strategies to improve patient symptom recognition, self-care behaviors and treatment seeking are necessary to improve overall health outcomes.

The aim of this pilot study was to test the feasibility of a wireless health monitoring device and cell phone app in 10 patients (5 with COPD and 5 with HF). This collaborative multidisciplinary study is innovative in its inclusion of the patient as an active partner in the use of technology to monitor changes in physiologic indicators to alert them to baseline status changes and guide self-care decision-making. The nurse-engineer team worked to develop devices that met the data collection needs of the research team, while being mindful of comfort and body image concerns of the patient. Additionally, the engineers provided the nurse researchers essential training on troubleshooting technology problems in the field. Weekly home visits with participants provided ongoing feedback that impacted design decisions and revisions throughout the data collection period.

Data were collected on self-care (SCHFI) at enrollment and post intervention. Participants had a mean age of 67.7 + 11.9 years, EF of 26.5 + 11.8, 60% male, 70% married. Mixed between-within subjects’ analysis of variance was conducted to test the impact of the intervention on the participant’s self-care scores. There was no significant interaction between group and time, Wilk’s Lambda = .97, F (1, 17) = .46, p = .51. There was no significant main effect for time Wilk’s Lambda = .94, F (1, 17) = 1.14, p = .30. Self-care maintenance (31 vs 31.7), management (49.2 vs 63) and confidence (58.2 vs 58.7) scores were inadequate at each time but did increase after intervention.

A Reduced Order Model For Efficient Physiological Flow Analysis In Aneurysms by Proper Orthogonal Decomposition

Fri, 05/20/2016 - 3:30pm

Simulating physiological flows using computational fluid dynamics (CFD) remains to be computationally expensive and difficult for clinical usage because of the physiological flow and geometrical complexity involved in patient specific situations. We use the reduced order modeling (ROM) of such systems with high nonlinearity and geometrical non-uniformity to replace the full, nonlinear model with a low-degrees of freedom ROM model. We construct ROM models by the proper orthogonal decomposition (POD) method to estimate the flow-induced wall shear stress (WSS) and pressure loading of a simplified abdominal aortic aneurysm and a bifurcation cerebral aneurysm. This method allows us to investigate a wide range of different physiological flow parameters without conducting the computationally expensive CFD simulations repetitively, which is promising for clinical usage.

We obtain a set of snapshots from a set of flow simulations with multiple variable parameters, called the training set. The training set should be simulated in a parameter space that contains all the physiological parameters of interest. We show that both the velocity and pressure distributions are well reconstructed when compared with the exact values with a small number of modes. A mesh-less shell model is used to estimate the aneurysm sidewall’s in-plane stresses. Sidewalls with non-uniform thickness are considered to study the influence of local weakness on the aneurysm’s risk of failure. We found that the sensitivity of the material’s strength to the local weakness depends on the aneurysms sidewall’s Gaussian curvatures, the curvature to thickness ratio and the distribution of the flow loading. It is therefore critical to describe the distribution of curvature and thickness accurately when estimating the in-plane stress of aneurysms.

Utilizing the Green Nursing Project Initiative to Educate Nurses about Health Effects Related to Exposure of Chemicals Contained in Household and Personal Care Products and to Inspire Them to Take Action

Fri, 05/20/2016 - 3:30pm

Consumers are exposed to a variety of environmental chemicals including carcinogens, reproductive toxins, and endocrine disrupting chemicals from everyday use of common household and personal care products. Evidence supports concern that exposures to low doses or the combination of low doses of chemicals can pose a health risk for the general population as well as for vulnerable populations. Gaps exist in translating this information to the public and helping people understand the health effects related to chemical exposures and personal actions they could take to reduce exposures.

There are 2.6 million nurses in the U.S. who have direct access to numerous patient populations. Educating and utilizing nurses as a conduit for information-sharing related to environmental health issues could fill the gap, influence health outcomes, and contribute to sustainable communities.

A Speaker’s Bureau was constructed under the Central Mass Health Literacy Project to facilitate community access to health literacy topics. The Green Nursing Project is an initiative to educate hundreds of nurses about Environmental Health Literacy topics and Inspire them to take Personal and Professional Action. The Green Nursing Project includes Hands-on Interactive Workshops to introduce participants to chemicals in consumer products, adverse health effects, and risk reduction strategies.

Implantable Microenvironments to Capture Stable-to- Aggressive Tumor Transition

Fri, 05/20/2016 - 3:30pm

Clinical stability occurs when cancers reach a state where the disease neither advances nor regresses. Tumors can remain in this state for multiple years before progressing to more aggressive phenotypes. The mechanisms for maintaining a stable state and the factors that contribute to tumor activation are poorly understood. We hypothesized that an implantable biomaterial scaffold would be able to isolate a population of stable tumor cells that could then be used to study the transition to an aggressive phenotype. In this work we developed a tunable and highly controlled, porous acrylamide scaffold and subcutaneously implanted them in immunodeficient (NSG) mice. Prior to implantation scaffolds were seeded with a variety of different cell types. Specifically, human bone marrow stromal cells were supplemented with mouse stromal cells genetically engineered to express human cytokines to promote the generation of different tissue microenvironments in the scaffolds. After implantation the mice received an orthotopic injection of either human breast or prostate cancer cells. The tumors were allowed to generate metastases to the scaffolds and other tissues. Scaffolds were transplanted to non-tumor bearing mice once the tumor burden became exhaustive to the host to allow for further study of the microenvironment. The role of immune cells on the tumor microenvironment was also explored. Human peripheral blood mononuclear cells were isolated from donors and injected intravenously prior to transplantation. Bioluminescent imaging was used to capture tumor growth in vivo over a ten week period. The scaffolds were analyzed via immunohistochemical staining on thinly sectioned tissue and intact tissue cleared samples to characterize the tissue microenvironment and its effect on tumor progression. Our work has demonstrated the application of implantable tissue engineered microenvironments to study the phenomena of tumor stability in vivo and has uncovered some potentially important factors that drive the transition from stable to aggressive tumors.

Prospective Relations between Red Blood Cell ω-6 and ω-3 Fatty Acid Composition and Cognitive Function among Older Puerto Rican Adults

Fri, 05/20/2016 - 3:30pm

Objectives: To examine the association between red blood cell (RBC) ω-6 and ω-3 fatty acid (FA) composition and cognitive function over 2-y follow-up among older U.S. mainland Puerto Ricans.

Methods: Data are from the Boston Puerto Rican Health Study (74% female; 57±8 y). RBC membrane FA status was ascertained at baseline. Individual FA were expressed as a percentage of total FA identified. Cognitive function was measured at baseline and at 2-y using the Mini-Mental State Exam (MMSE), where a higher score ranging from 0-30 indicates better function. Cognitive impairment was defined as MMSE scores ≤21, ≤23, and ≤24 for those with less than a 9th grade education, a 9th to 12th grade education, and some college education or higher, respectively. Relations between FA and MMSE scores were examined in 946 participants and incidence of cognitive impairment among those considered to be cognitively normal at baseline (n=639).

Results: In multivariate models additionally adjusted for baseline MMSE, total ω-6 FA (quartiles) were associated with lower MMSE score at 2-y (P-trend=0.003). Total ω-3 FA were positively (P-trend=0.04) and the ω-6:ω-3 ratio inversely (P-trend=0.007) related to 2-y MMSE, but these relationships attenuated with adjustment for baseline score. The incidence of cognitive impairment at follow-up was 22%. In multivariate models, a 1% increase in total ω-6 FA related to a 9% greater incidence of cognitive impairment [RR=1.09 (95% CI: 1.00, 1.18), P=0.04]. Total ω-3 FA were inversely related to incident cognitive impairment [RR=0.92 (0.81 to 1.05), P=0.21], whereas the ω-6:ω-3 ratio was positively associated [RR=1.12 (95% CI: 0.98, 1.26), P=0.08].

Conclusions: An objective biomarker of ω-6 FA consumption was associated with poorer cognitive function and incidence of cognitive impairment over 2-y follow-up, suggesting that greater intakes of food sources of ω-6 FA may play a role in cognitive decline among older U.S. mainland Puerto Ricans.

Poster Session Program: 2016 UMass Center for Clinical and Translational Science Research Retreat

Fri, 05/20/2016 - 3:30pm

Poster Session Program for the 6th annual UMass Center for Clinical and Translational Science Research Retreat, held Friday, May 20, 2016 at the University of Massachusetts Medical School, Worcester, MA.

View poster abstracts

Race/Sex Group Modification of the Association between Allostatic Load and Depression: Findings from the National Health and Nutrition Examination Survey, 2005-2010

Fri, 05/20/2016 - 3:30pm

Objective: We assessed whether the relationship between depression and chronic stress as measured in allostatic load (AL) differs by race and sex among US black and white adults.

Methods: Using data from the National Health and Nutrition Examination Survey (NHANES) 2005-2010, we examined race/sex modification of the relationship between AL and depression in black and white women and men aged 18-64 years (n=6431). AL scores, ranging from 0-9, were calculated using 9 cardiovascular, metabolic, and immunologic biomarkers; scores ≥ 4 were considered “high-risk”. Depression was assessed using the PHQ-9; scores ≥ 10 indicate clinical depression. Logistic regression models estimated odds of elevated depressive symptoms as a function of AL for each race/sex group; age and socioeconomic status were included as covariates in each model. All analyses were weighted to represent U.S. adults.

Results: The association between AL and depression was strongest among white women (OR=2.1, 95% CI: 1.5, 3.0), followed by black men (OR=1.7 95% CI: 1.0, 2.9), and not statistically significant among black women (OR=1.1 95% CI: .60, 2.0) or white men (OR=1.4 95% CI: .82, 2.5).

Conclusions: Our findings that the association between AL and depression was strongest and statistically significant only among white women and black men despite black women having the highest mean AL and depression scores suggests a measure of psychological resistance to chronic stress among those coping with intersecting pressures of systemic race and gender-based discrimination. These results also suggest that social inequality may shape the manner in which chronic stress is expressed. Further research should explore other potential racialized and gendered manifestations of chronic stress in order to better understand social factors influencing health inequity.

Plasma PLP Concentration and Depressive Symptomatology, over time, in older Latino Adults

Fri, 05/20/2016 - 3:30pm

Background: Low vitamin B-6 status has been linked to depressive symptomatology. However, most studies have been cross-sectional and may not have controlled for relevant confounders. Few studies have examined this association in Latino populations at high risk for major depression.

Design: We used two-level hierarchical linear regression models (HLM) for continuous outcomes. Level-1 data included three measures of participant’s depressive symptomatology collected at baseline, 2y follow-up and 5y follow-up. Participants constituted level-2 data. Vitamin B-6 was associated with depressive symptomatology across these time points.

Objective: We examined the longitudinal association of vitamin B-6 status with depressive symptomatology across 3 time points over ~ 5-7 y in a cohort of older Puerto Rican adults, a population previously identified to be at high risk for depressive symptomatology and clinical depression.

Results: Plasma pyridoxyl-5’-phosphate (PLP) concentration, a time-varying predictor, was significantly associated with depressive symptomatology. Study participants with PLP deficiency, vs. optimal PLP, had higher baseline depressive symptoms (22±14, vs. 20±13); this differential remained constant over time and persisted after controlling for age, sex, education, BMI, smoking and alcohol use, other relevant nutritional factors, perceived stress, stressful life events and allostatic load; and use of antidepressant medication. However, PLP concentration was not associated with the rate of change in depressive symptomatology over time.

Conclusions: Suboptimal plasma PLP is associated with higher depressive symptomatology in older Puerto Rican adults and this appears to persist over time. Our data suggest that identification and treatment of vitamin B-6 deficiency may be a useful preventive and intervention approach in this population.

Piloting Signs of Safety: A Deaf-Accessible Toolkit for Trauma and Addiction

Fri, 05/20/2016 - 3:30pm

The Deaf community - a minority group of 500,000 Americans who use American Sign Language (ASL) - experiences trauma and addiction at rates double to the general population. Yet, there are no evidence-based treatments that have been evaluated to treat trauma, addiction, or other behavioral health conditions among Deaf people.

Current evidence-based treatments fail to meet the needs of Deaf clients. One example is Seeking Safety, a well-validated therapy for people recovering from trauma and addiction. Seeking Safety includes a therapist guide and client handouts for 25 therapy sessions, each teaching clients a safe coping skill. When Seeking Safety was used with Deaf clients, unique barriers were revealed with regard to the client materials: they were presented in complex English instead of ASL, nor sensitive to Deaf people’s culture, social norms, and history of oppression.

To address these barriers, Dr. Anderson assembled a team of Deaf and hearing researchers, clinicians, filmmakers, actors, artists, and Deaf people in recovery to develop Signs of Safety, a Deaf-accessible toolkit to be used with Seeking Safety. Signs of Safety is comprised of a therapist companion guide and population-specific client materials, including visual handouts and ASL teaching stories on digital video, which present key learning points via an “educational soap opera.”

Dr. Anderson is currently leading a pilot study of Signs of Safety. Preliminary results show that participants are reporting symptom reduction from baseline to follow-up and high levels of satisfaction with the model, giving us the confidence to further pursue this line of research.

Agenda: 2016 UMass Center for Clinical and Translational Science Research Retreat

Fri, 05/20/2016 - 10:30am

Agenda for the 6th annual UMass Center for Clinical and Translational Science Research Retreat, held Friday, May 20, 2016 at the University of Massachusetts Medical School, Worcester, MA.

Developing an Adeno-Associated Viral Vector (AAV) Toolbox for CNS Gene Therapy: A Dissertation

Thu, 05/19/2016 - 4:08pm

Neurological disorders – disorders of the brain, spine and associated nerves – are a leading contributor to global disease burden with a sizable economic cost. Adeno-associated viral (AAV) vectors have emerged as an effective platform for CNS gene therapy and have shown early promise in clinical trials. These trials involve direct infusion into brain parenchyma, an approach that may be suboptimal for treatment of neurodegenerative disorders, which often involve more than a single structure in the CNS. However, overall neuronal transduction efficiency of vectors derived from naturally occurring AAV capsids after systemic administration is relatively low. We have developed novel capsids AAV-AS and AAV-B1 that lead to widespread gene delivery throughout the brain and spinal cord, particularly to neuronal populations. Both transduce the adult mouse brain >10-fold more efficiently than the clinical gold standard AAV9 upon intravascular infusion, with gene transfer to multiple neuronal sub-populations. These vectors are also capable of neuronal transduction in a normal cat. We have demonstrated the efficacy of AAV-AS in the context of Huntington's disease by knocking down huntingtin mRNA 33-50% after a single intravenous injection, which is better than what can be achieved by AAV9 at the particular dose. AAVB1 additionally transduces muscle, beta cells, pulmonary alveoli and retinal vasculature at high efficiency, and has reduced sensitivity to neutralizing antibodies in human sera. Generation of this vector toolbox represents a major step towards gaining genetic access to the entire CNS, and provides a platform to develop new gene therapies for neurodegenerative disorders.

Systematic Dissection of Roles for Chromatin Regulators in Dynamics of Transcriptional Response to Stress in Yeast: A Dissertation

Thu, 05/19/2016 - 4:08pm

The following work demonstrates that chromatin regulators play far more pronounced roles in dynamic gene expression than they do in steady-state. Histone modifications have been associated with transcription activity. However, previous analyses of gene expression in mutants affecting histone modifications show limited alteration. I systematically dissected the effects of 83 histone mutants and 119 gene deletion mutants on gene induction/repression in response to diamide stress in yeast. Importantly, I observed far more changes in gene induction/repression than changes in steady-state gene expression. The extensive dynamic gene expression profile of histone mutants and gene deletion mutants also allowed me to identify specific interactions between histone modifications and chromatin modifiers. Furthermore, by combining these functional results with genome-wide mapping of several histone modifications in the same time course, I was able to investigate the correspondence between histone modification occurrence and function. One such observation was the role of Set1-dependent H3K4 methylation in the repression of ribosomal protein genes (RPGs) during multiple stresses. I found that proper repression of RPGs in stress required the presence, but not the specific sequence, of an intron, an element which is almost unique to this gene class in Saccharomyces cerevisiae. This repression may be related to Set1’s role in antisense RNA-mediated gene silencing. Finally, I found a potential role for Set1 in producing or maintaining uncapped mRNAs in cells through a mechanism that does not involved nuclear exoribonucleases. Thus, deletion of Set1 in xrn1Δ suppresses the accumulation of uncapped transcripts observed in xrn1Δ. These findings reveal that Set1, along with other chromatin regulators, plays important roles in dynamic gene expression through diverse mechanisms and thus provides a coherent means of responding to environmental cues.

Distracted Practice and Patient Safety: The Healthcare Team Experience: A Dissertation

Thu, 05/19/2016 - 3:20pm

Purpose: The purpose of this study was to explore the experiences of distracted practice across the healthcare team.

Definition: Distracted practice is the diversion of a portion of available cognitive resources that may be needed to effectively perform/carry out the current activity.

Background: Distracted practice is the result of individuals interacting with the healthcare team, the environment and technology in the performance of their jobs. The resultant behaviors can lead to error and affect patient safety.

Methods: A qualitative descriptive (QD) approach was used that integrated observations with semi-structured interviews. The conceptual framework was based on the distracted driving model and a completed concept analysis.

Results: There were 22 observation sessions and 32 interviews (12 RNs, 11 MDs, and 9 Pharmacists) completed between December, 2014 and July 2015. Results suggested that distracted practice is based on the main theme of cognitive resources which varies by the subthemes of individual differences; environmental disruptions; team awareness; and “rush mode”/time pressure.

Conclusions and Implications: Distracted practice is an individual human experience that occurs when there are not enough cognitive resources available to effectively complete the task at hand. In that moment an individual shifts from thinking critically, being able to complete their current task without error, to not thinking critically and working in an automatic mode. This is when errors occur. Additional research is needed to evaluate intervention strategies to reduce and prevent distracted practice.

Techniques in distal access of wide-necked giant intracranial aneurysms during treatment with flow diversion

Tue, 05/17/2016 - 12:38pm

BACKGROUND: Accessing the normal distal vessel in treatment of wide-necked giant intracranial aneurysms with flow diversion can be difficult.

CASE DESCRIPTION: Through illustrative cases, the authors present several useful techniques in distal access of wide-necked giant aneurysms during flow diversion treatment. Obtaining an optimal projection that separates the outflow limb from the aneurysm is most critical. Each of the three techniques described enabled the distal access to giant intracranial aneurysms during treatment with flow diversion.

CONCLUSION: The looped-around technique, balloon-assisted technique, and retrograde access are valuable strategies in crossing the aneurysm if direct distal access cannot be obtained.

Biosimilars in rheumatology: what the clinician should know

Tue, 05/17/2016 - 12:37pm

Biosimilars are now a reality in rheumatology. Although analytical and non-clinical procedures to establish similarity have evolved significantly, clinical trials demonstrating equivalent efficacy and safety are absolutely required for all biosimilars. The design of such trials, including equivalence and non-inferiority statistical approaches, are discussed. Clinical evidence on biosimilars that have been approved recently or are presently being developed for use in rheumatology is also reviewed and contrasted with that available for biomimics (or intended copies), which are non-innovator biologics that are marketed in several countries but have not undergone review according to a regulatory pathway for biosimilars.

Curcumin Ingestion Inhibits Mastocytosis and Suppresses Intestinal Anaphylaxis in a Murine Model of Food Allergy

Tue, 05/17/2016 - 12:37pm

IgE antibodies and mast cells play critical roles in the establishment of allergic responses to food antigens. Curcumin, the active ingredient of the curry spice turmeric, has anti-inflammatory properties, and thus may have the capacity to regulate Th2 cells and mucosal mast cell function during allergic responses. We assessed whether curcumin ingestion during oral allergen exposure can modulate the development of food allergy using a murine model of ovalbumin (OVA)-induced intestinal anaphylaxis. Herein, we demonstrate that frequent ingestion of curcumin during oral OVA exposure inhibits the development of mastocytosis and intestinal anaphylaxis in OVA-challenged allergic mice. Intragastric (i.g.) exposure to OVA in sensitized BALB/c mice induced a robust IgE-mediated response accompanied by enhanced OVA-IgE levels, intestinal mastocytosis, elevated serum mMCP-1, and acute diarrhea. In contrast, mice exposed to oral curcumin throughout the experimental regimen appeared to be normal and did not exhibit intense allergic diarrhea or a significant enhancement of OVA-IgE and intestinal mast cell expansion and activation. Furthermore, allergic diarrhea, mast cell activation and expansion, and Th2 responses were also suppressed in mice exposed to curcumin during the OVA-challenge phase alone, despite the presence of elevated levels of OVA-IgE, suggesting that curcumin may have a direct suppressive effect on intestinal mast cell activation and reverse food allergy symptoms in allergen-sensitized individuals. This was confirmed by observations that curcumin attenuated the expansion of both adoptively transferred bone marrow-derived mast cells (BMMCs), and inhibited their survival and activation during cell culture. Finally, the suppression of intestinal anaphylaxis by curcumin was directly linked with the inhibition of NF-kappaB activation in curcumin-treated allergic mice, and curcumin inhibited the phosphorylation of the p65 subunit of NF-kappaB in BMMCs. In summary, our data demonstrates a protective role for curcumin during allergic responses to food antigens, suggesting that frequent ingestion of this spice may modulate the outcome of disease in susceptible individuals.

Endometriosis and ovarian cancer: links, risks, and challenges faced

Tue, 05/17/2016 - 12:37pm

Endometriosis is a benign gynecological condition characterized by specific histological, molecular, and clinical findings. It affects 5%-10% of premenopausal women, is a cause of infertility, and has been implicated as a precursor for certain types of ovarian cancer. Advances in technology, primarily the ability for whole genome sequencing, have led to the discovery of new mutations and a better understanding of the function of previously identified genes and pathways associated with endometriosis associated ovarian cancers (EAOCs) that include PTEN, CTNNB1 (beta-catenin), KRAS, microsatellite instability, ARID1A, and the unique role of inflammation in the development of EAOC. Clinically, EAOCs are associated with a younger age at diagnosis, lower stage and grade of tumor, and are more likely to occur in premenopausal women when compared with other ovarian cancers. A shift from screening strategies adopted to prevent EAOCs has resulted in new recommendations for clinical practice by national and international governing bodies. In this paper, we review the common histologic and molecular characteristics of endometriosis and ovarian cancer, risks associated with EAOCs, clinical challenges and give recommendations for providers.

Decade-long trends (1999-2009) in the characteristics, management, and hospital outcomes of patients hospitalized with acute myocardial infarction with prior diabetes and chronic kidney disease

Tue, 05/17/2016 - 12:37pm

BACKGROUND: Despite the increasing magnitude and impact, there are limited data available on the clinical management and in-hospital outcomes of patients who have diabetes mellitus (DM) and chronic kidney disease (CKD) at the time of hospitalization for acute myocardial infarction (AMI). The objectives of our population-based observational study in residents of central Massachusetts were to describe decade-long trends (1999-2009) in the characteristics, in-hospital management, and hospital outcomes of AMI patients with and without these comorbidities.

METHODS: We reviewed the medical records of 6,018 persons who were hospitalized for AMI on a biennial basis between 1999 and 2009 at all eleven medical centers in central Massachusetts. Our sample consisted of the following four groups: DM with CKD (n=587), CKD without DM (n=524), DM without CKD (n=1,442), and non-DM/non-CKD (n=3,465).

RESULTS: Diabetic patients with CKD were more likely to have a higher prevalence of previously diagnosed comorbidities, to have developed heart failure acutely, and to have a longer hospital stay compared with non-DM/non-CKD patients. Between 1999 and 2009, there were marked increases in the prescribing of beta-blockers, statins, and aspirin for patients with CKD and DM as compared to those without these comorbidities. In-hospital death rates remained unchanged in patients with DM and CKD, while they declined markedly in patients with CKD without DM (20.2% dying in 1999; 11.3% dying in 2009).

CONCLUSION: Despite increases in the prescribing of effective cardiac medications, AMI patients with DM and CKD continue to experience high in-hospital death rates.

The origin of glutamatergic synaptic inputs controls synaptic plasticity and its modulation by alcohol in mice nucleus accumbens

Tue, 05/17/2016 - 12:37pm

It is widely accepted that long-lasting changes of synaptic strength in the nucleus accumbens (NAc), a brain region involved in drug reward, mediate acute and chronic effects of alcohol. However, our understanding of the mechanisms underlying the effects of alcohol on synaptic plasticity is limited by the fact that the NAc receives glutamatergic inputs from distinct brain regions (e.g., the prefrontal cortex (PFCx), the amygdala and the hippocampus), each region providing different information (e.g., spatial, emotional and cognitive). Combining whole-cell patch-clamp recordings and the optogenetic technique, we examined synaptic plasticity, and its regulation by alcohol, at cortical, hippocampal and amygdala inputs in fresh slices of mouse tissue. We showed that the origin of synaptic inputs determines the basic properties of glutamatergic synaptic transmission, the expression of spike-timing dependent long-term depression (tLTD) and long-term potentiation (LTP) and long-term potentiation (tLTP) and their regulation by alcohol. While we observed both tLTP and tLTD at amygadala and hippocampal synapses, we showed that cortical inputs only undergo tLTD. Functionally, we provide evidence that acute Ethyl Alcohol (EtOH) has little effects on higher order information coming from the PFCx, while severely impacting the ability of emotional and contextual information to induce long-lasting changes of synaptic strength.

FIB/SEM technology and high-throughput 3D reconstruction of dendritic spines and synapses in GFP-labeled adult-generated neurons

Tue, 05/17/2016 - 12:36pm

The fine analysis of synaptic contacts is usually performed using transmission electron microscopy (TEM) and its combination with neuronal labeling techniques. However, the complex 3D architecture of neuronal samples calls for their reconstruction from serial sections. Here we show that focused ion beam/scanning electron microscopy (FIB/SEM) allows efficient, complete, and automatic 3D reconstruction of identified dendrites, including their spines and synapses, from GFP/DAB-labeled neurons, with a resolution comparable to that of TEM. We applied this technology to analyze the synaptogenesis of labeled adult-generated granule cells (GCs) in mice. 3D reconstruction of dendritic spines in GCs aged 3-4 and 8-9 weeks revealed two different stages of dendritic spine development and unexpected features of synapse formation, including vacant and branched dendritic spines and presynaptic terminals establishing synapses with up to 10 dendritic spines. Given the reliability, efficiency, and high resolution of FIB/SEM technology and the wide use of DAB in conventional EM, we consider FIB/SEM fundamental for the detailed characterization of identified synaptic contacts in neurons in a high-throughput manner.