Nanoconnectomic upper bound on the variability of synaptic plasticity

Information in a computer is quantified by the number of bits that can be stored and recovered. An important question about the brain is how much information can be stored at a synapse through synaptic plasticity, which depends on the history of probabilistic synaptic activity. The strong correlation between size and efficacy of a synapse allowed us to estimate the variability of synaptic plasticity. In an EM reconstruction of hippocampal neuropil we found single axons making two or more synaptic contacts onto the same dendrites, having shared histories of presynaptic and postsynaptic activity. The spine heads and neck diameters, but not neck lengths, of these pairs were nearly identical in size. We found that there is a minimum of 26 distinguishable synaptic strengths, corresponding to storing 4.7 bits of information at each synapse. Because of stochastic variability of synaptic activation the observed precision requires averaging activity over several minutes

Coordinated structural plasticity across synapses in the adult hippocampus

textNeural circuitry is determined primarily by trillions of synaptic junctions that link cells in the nervous system. Understanding how the structure of the synapse influences its function has been a central goal of cellular neuroscience since synapses were first recognized more than a century ago. Long-term potentiation (LTP), a long lasting enhancement of synaptic efficacy, is a well-characterized cellular correlate of learning and memory that results in dramatic structural remodeling of the synapse. Research has focused heavily on the postsynaptic structural remodeling that occurs to support LTP, but concomitant presynaptic and subcellular remodeling during LTP has been left largely unexplored. To address these questions, three-dimensional reconstructions from serial section electron microscopy of presynaptic boutons, vesicle pools, and dendritic smooth endoplasmic reticulum (SER) in hippocampal area CA1 were created and quantified. The data presented in this dissertation demonstrate that coordinated structural plasticity occurs at both pre- and postsynaptic sides of adult hippocampal synapses by 2 hours during LTP induced with theta burst stimulation. Presynaptically, the number of presynaptic boutons correlated perfectly with fewer dendritic spines during LTP that were previously reported, suggesting that synaptic units act as cohesive structures. Vesicle pools were mobilized and vesicle transport packets were moved into boutons or were released in transit. Dendritic SER is a ubiquitous intracellular membranous network involved in calcium signaling and protein modification. The complexity of SER influences the movement of diffusible membrane cargo. SER was dramatically remodeled during LTP, redistributing from the shaft of the dendrite into spines and becoming highly complex near synapses that were largest during LTP. As a preliminary investigation into how normal mechanisms of structural plasticity described in this dissertation might go awry under conditions of synaptic pathology, three-dimensional reconstructions of CA1 synaptic ultrastructure in a mouse model of Fragile X, which is known to express exaggerated mGluR-dependent long-term depression (LTD), were created and quantified. Synaptic ultrastructure was similar with that of the wild-type mouse, suggesting that structural malformation in FX might be confined to development or to other brain regions.Neuroscienc

Estimating Mean Pulmonary Wedge Pressure in Patients With Chronic Atrial Fibrillation From Transthoracic Doppler Indexes of Mitral and Pulmonary Venous Flow Velocity

AbstractObjectives. We sought to obtain a noninvasive estimation of mean pulmonary wedge pressure (MPWP) in patients with chronic atrial fibrillation (AF).Background. It has previously been demonstrated that MPWP can be reliably estimated from Doppler indexes of mitral and pulmonary venous flow (PVF) in patients with sinus rhythm. Doppler estimation of MPWP has not been validated in patients with AF.Methods. MPWP was correlated with variables of mitral and pulmonary venous flow velocity as assessed by Doppler transthoracic echocardiography in 35 consecutive patients. The derived algorithm was prospectively tested in 23 additional patients.Results. In all patients the mitral flow pattern showed only a diastolic forward component. A significant but relatively weak correlation (r = −0.50) was observed between MPWP and mitral deceleration time. In 12 (34%) of 35 patients, the pulmonary vein flow tracing demonstrated only a diastolic forward component; a diastolic and late systolic forward flow was noted in the remaining 23 patients (66%). A strong negative correlation was observed between MPWP and the normalized duration of the diastolic flow (r = −0.80) and its initial deceleration slope time (r = −0.91). Deceleration time >220 ms predicted MPWP ≤12 mm Hg with 100% sensitivity and 100% specificity. When estimating MPWP by using the equation MPWP= −94.261 PVF deceleration time− 9.831 Interval QRS to onset of diastolic PVF− 16.337 Duration of PVF+ 44.261, the measured and predicted MPWP closely agreed with a mean difference of −0.85 mm Hg. The 95% confidence limits were 4.8 and −6.1 mm Hg.Conclusions. In patients with chronic AF, MPWP can be estimated from transthoracic Doppler study of PVF velocity signals.(J Am Coll Cardiol 1997;30:19–26

Recovery of distal coronary flow reserve in LAD and LCx after Y-Graft intervention assessed by transthoracic echocardiography

<p>Abstract</p> <p>Background</p> <p>Y- graft (Y-G) is a graft formed by the Left Internal Mammary Artery (LIMA) connected to the Left Anterior Descending Artery (LAD) and by a free Right Internal Mammary Artery (RIMA) connected to LIMA and to a Marginal artery of Left Circumflex Artery (LCx). Aim of the work was to study the flow of this graft during a six months follow-up to assess whether the graft was able to meet the request of all the left coronary circulation, and to assess whether it could be done by evaluation of coronary flow reserve (CFR).</p> <p>Methods</p> <p>In 13 consecutive patients submitted to Y-G (13 men), CFR was measured in distal LAD and in distal LCx from 1 week after , every two months, up to six months after operation (a total of 8 tests for each patient) by means of transthoracic echocardiography (TTE) and Adenosine infusion (140 mcg/kg/min for 3-6 min). A Sequoia 256, Acuson-Siemens, was used. Contrast was used when necessary (Levovist 300 mg/ml solution at a rate of 0,5-1 ml/min). Max coronary flow diastolic velocity post-/pre-test ≥2 was considered normal CFR.</p> <p>Results</p> <p>Coronary arteriography revealed patency of both branches of Y-G after six months. Accuracy of TTE was 100% for LAD and 85% for LCx. Feasibility was 100% for LAD and 85% for LCx. CFR improved from baseline in LAD (2.21 ± 0.5 to 2.6 ± 0.5, p = 0.03) and in LCx (1.7 ± 1 to 2.12 ± 1, p = 0.05). CFR was under normal at baseline in 30% of patients <it>vs </it>8% after six months in LAD (p = 0.027), and in 69% of patients <it>vs </it>30% after six months in LCx (p = 0.066).</p> <p>Conclusion</p> <p>CFR in Y-G is sometimes reduced in both left territories postoperatively but it improves at six months follow-up. A follow-up can be done non-invasively by TTE and CFR evaluation.</p