Feed-forward Inhibitory Circuits in Hippocampus and Their Computational Role in Fragile X Syndrome

Feed-forward inhibitory (FFI) circuits are canonical neural microcircuits. They are unique in that they are comprised of excitation rapidly followed by a time-locked inhibition. This sequence provides for a powerful computational tool, but also a challenge in the analysis and study of these circuits. In this work, mechanisms and computations of two hippocampal FFI circuits have been examined. Specifically, the modulation of synaptic strength of the excitation and the inhibition is studied during constant-frequency and naturalistic stimulus patterns to reveal how FFI circuit properties and operations are dynamically modulated during ongoing activity. In the first part, the FFI circuit dysfunction in the mouse model of Fragile X syndrome, the leading genetic cause of autism, is explored. The balance between excitation and inhibition is found to be markedly abnormal in the Fmr1 KO mouse, leading to failure of FFI circuit to perform spike modulation tasks properly. The mechanisms underlying FFI circuit dysfunction are explored and a critical role of presynaptic GABAB receptors is revealed. Specifically, excessive presynaptic GABA receptor signaling is found to suppress GABA release in a subset of hippocampal interneurons leading to excitation/inhibition imbalance. In the second part, the dynamic changes during input bursts are explored both experimentally and in a simulated circuit. Because of the short-term synaptic plasticity of individual circuit components, the burst is found to play an important role in the modulating precision of the output cell spiking. The role of dynamics balance of excitation and inhibition during bursts in output spiking precision is further explored. Overall, the balance of excitation and inhibition is found to be critical for FFI circuit performance

Association of Left Atrial Function Index with Atrial Fibrillation and Cardiovascular Disease: The Framingham Offspring Study

BACKGROUND: Left atrial (LA) size, a marker of atrial structural remodeling, is associated with increased risk for atrial fibrillation (AF) and cardiovascular disease (CVD). LA function may also relate to AF and CVD, irrespective of LA structure. We tested the hypothesis that LA function index (LAFI), an echocardiographic index of LA structure and function, may better characterize adverse LA remodeling and predict incident AF and CVD than existing measures. METHODS AND RESULTS: In 1786 Framingham Offspring Study eighth examination participants (mean age, 66+/-9 years; 53% women), we related LA diameter and LAFI (derived from the LA emptying fraction, left ventricular outflow tract velocity time integral, and indexed maximal LA volume) to incidence of AF and CVD on follow-up. Over a median follow-up of 8.3 years (range, 7.5-9.1 years), 145 participants developed AF and 139 developed CVD. Mean LAFI was 34.5+/-12.7. In adjusted Cox regression models, lower LAFI was associated with higher risk of incident AF (hazard ratio=3.83, 95% confidence interval=2.23-6.59, lowest [Q1] compared with highest [Q4] LAFI quartile) and over 2-fold higher risk of incident CVD (hazard ratio=2.20, 95% confidence interval=1.32-3.68, Q1 versus Q4). Addition of LAFI, indexed maximum LA volume, or LA diameter to prediction models for AF or CVD did not significantly improve model discrimination for either outcome. CONCLUSIONS: In our prospective investigation of a moderate-sized community-based sample, LAFI, a composite measure of LA size and function, was associated with incident AF and CVD. Addition of LAFI to the risk prediction models for AF or CVD, however, did not significantly improve their performance

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IPRO 321 has the task of facilitating the performance of undergraduate research in the Illinois Institute of Technology (IIT) by creating a website called ResearchWeb that integrates and connects undergraduates with colleagues, faculty members and resources.Deliverable

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IPRO 321 has the task of facilitating the performance of undergraduate research in the Illinois Institute of Technology (IIT) by creating a website called ResearchWeb that integrates and connects undergraduates with colleagues, faculty members and resources.Deliverable

Research Web (Semester Unknown) IPRO 321

IPRO 321 has the task of facilitating the performance of undergraduate research in the Illinois Institute of Technology (IIT) by creating a website called ResearchWeb that integrates and connects undergraduates with colleagues, faculty members and resources.Deliverable

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IPRO 321 has the task of facilitating the performance of undergraduate research in the Illinois Institute of Technology (IIT) by creating a website called ResearchWeb that integrates and connects undergraduates with colleagues, faculty members and resources.Deliverable

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IPRO 321 has the task of facilitating the performance of undergraduate research in the Illinois Institute of Technology (IIT) by creating a website called ResearchWeb that integrates and connects undergraduates with colleagues, faculty members and resources.Deliverable

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IPRO 321 has the task of facilitating the performance of undergraduate research in the Illinois Institute of Technology (IIT) by creating a website called ResearchWeb that integrates and connects undergraduates with colleagues, faculty members and resources.Deliverable