A voltage-based Event-Timing-Dependent Plasticity rule accounts for LTP subthreshold and suprathreshold for dendritic spikes in CA1 pyramidal neurons.

Long-term potentiation (LTP) is a synaptic mechanism involved in learning and memory. Experiments have shown that dendritic sodium spikes (Na-dSpikes) are required for LTP in the distal apical dendrites of CA1 pyramidal cells. On the other hand, LTP in perisomatic dendrites can be induced by synaptic input patterns that can be both subthreshold and suprathreshold for Na-dSpikes. It is unclear whether these results can be explained by one unifying plasticity mechanism. Here, we show in biophysically and morphologically realistic compartmental models of the CA1 pyramidal cell that these forms of LTP can be fully accounted for by a simple plasticity rule. We call it the voltage-based Event-Timing-Dependent Plasticity (ETDP) rule. The presynaptic event is the presynaptic spike or release of glutamate. The postsynaptic event is the local depolarization that exceeds a certain plasticity threshold. Our model reproduced the experimentally observed LTP in a variety of protocols, including local pharmacological inhibition of dendritic spikes by tetrodotoxin (TTX). In summary, we have provided a validation of the voltage-based ETDP, suggesting that this simple plasticity rule can be used to model even complex spatiotemporal patterns of long-term synaptic plasticity in neuronal dendrites.

Safety and Efficacy of the Transaxillary Access for Minimally Invasive Mitral Valve Surgery-A Propensity Matched Competitive Analysis.

Background and Objectives: Transaxillary access is a straightforward "single incision­direct vision" concept, based on a 5 cm skin incision in the right anterior axillary line. It is suitable for aortic, mitral and tricuspid surgery. The present study evaluates the hospital outcomes of the transaxillary access for isolated mitral valve surgery compared with full sternotomy. Patients and Methods: The final study group included 480 patients. A total of 160 consecutive transaxillary patients served as treatment group (MICS-MITRAL). Based on a multivariate logistic regression model including age, sex, body-mass-index, EuroScore II and LVEF, a 1:2 propensity matched control-group (n = 320) was generated out of 980 consecutive sternotomy patients. Redo surgeries, endocarditis or combined procedures were excluded. The mean age was 66.6 ± 10.6 years, 48.6% (n = 234) were female. EuroSCORE II averaged 1.98 ± 1.4%. Results: MICS-MITRAL had longer perfusion (88.7 ± 26.6 min vs. 68.7 ± 32.7 min; p < 0.01) and cross-clamp (64.4 ± 22.3 min vs. 49.7 ± 22.4 min; p < 0.01) times. This did not translate into longer procedure times (132 ± 31 min vs. 131 ± 46 min; p = 0.76). Both groups showed low rates of failed repair (MICS-MITRAL: n = 6/160; 3.75%; Sternotomy: n = 10/320; 3.1%; p = 0.31). MICS-MITRAL had lower transfusion rates (p ≤ 0.001), less re-exploration for bleeding (p = 0.04), shorter ventilation times (p = 0.02), shorter ICU-stay (p = 0.05), less postoperative hemofiltration (p < 0.01) compared to sternotomy patients. No difference was seen in the incidence of stroke (p = 0.47) and postoperative delirium (p = 0.89). Hospital mortality was significantly lower in MICS-MITRAL patients (0.0% vs. 3.4%; p = 0.02). Conclusions: The transaxillary access for MICS-MITRAL provides superior cosmetics and excellent clinical outcomes. It can be performed at least as safely and in the same time frame as conventional mitral surgery by sternotomy.

Contributions by metaplasticity to solving the Catastrophic Forgetting Problem.

Catastrophic forgetting (CF) refers to the sudden and severe loss of prior information in learning systems when acquiring new information. CF has been an Achilles heel of standard artificial neural networks (ANNs) when learning multiple tasks sequentially. The brain, by contrast, has solved this problem during evolution. Modellers now use a variety of strategies to overcome CF, many of which have parallels to cellular and circuit functions in the brain. One common strategy, based on metaplasticity phenomena, controls the future rate of change at key connections to help retain previously learned information. However, the metaplasticity properties so far used are only a subset of those existing in neurobiology. We propose that as models become more sophisticated, there could be value in drawing on a richer set of metaplasticity rules, especially when promoting continual learning in agents moving about the environment.

A new reduced-morphology model for CA1 pyramidal cells and its validation and comparison with other models using HippoUnit.

Modeling long-term neuronal dynamics may require running long-lasting simulations. Such simulations are computationally expensive, and therefore it is advantageous to use simplified models that sufficiently reproduce the real neuronal properties. Reducing the complexity of the neuronal dendritic tree is one option. Therefore, we have developed a new reduced-morphology model of the rat CA1 pyramidal cell which retains major dendritic branch classes. To validate our model with experimental data, we used HippoUnit, a recently established standardized test suite for CA1 pyramidal cell models. The HippoUnit allowed us to systematically evaluate the somatic and dendritic properties of the model and compare them to models publicly available in the ModelDB database. Our model reproduced (1) somatic spiking properties, (2) somatic depolarization block, (3) EPSP attenuation, (4) action potential backpropagation, and (5) synaptic integration at oblique dendrites of CA1 neurons. The overall performance of the model in these tests achieved higher biological accuracy compared to other tested models. We conclude that, due to its realistic biophysics and low morphological complexity, our model captures key physiological features of CA1 pyramidal neurons and shortens computational time, respectively. Thus, the validated reduced-morphology model can be used for computationally demanding simulations as a substitute for more complex models.

Perioperative Course of Three-Dimensional-Derived Right Ventricular Strain in Coronary Artery Bypass Surgery: A Prospective, Observational, Pilot Trial.

OBJECTIVES: Few data exist on perioperative three-dimensional-derived right ventricular strain. The authors aimed to describe the perioperative course of three-dimensional-derived right ventricular strain in coronary artery bypass graft (CABG) surgery patients. DESIGN: Prospective, observational, pilot trial. SETTING: Single university hospital. PARTICIPANTS: The study comprised 40 patients with preserved left ventricular and right ventricular (RV) function undergoing isolated on-pump CABG surgery. INTERVENTIONS: Three-dimensional strain analysis and standard echocardiographic evaluation of RV function were performed preoperatively (T1) and postoperatively (T4) with transthoracic echocardiography (TTE) and intraoperatively before sternotomy (T2) and after sternotomy (T3) with transesophageal echocardiography (TEE). All echocardiographic measurements were performed under stable hemodynamic conditions and predefined fluid management without any vasoactive support. MEASUREMENTS AND MAIN RESULTS: The measurements of three-dimensional-derived RV free-wall strain (3D-RV FWS) and RV ejection fraction were performed using TomTec 4D RV-Function 2.0 software. Philips QLAB 10.8 was used to analyze tissue velocity of the tricuspid annulus, tricuspid annular systolic excursion, and RV fractional area change. There were no significant differences (median [interquartile range {IQR}]) between preoperative TTE and intraoperative TEE measurements for 3D-RV FWS (T1 v T2: -22.35 [IQR -17.70 to -27.22] v -24.35 [IQR -20.63 to -29.88]; not significant). 3D-RV FWS remained unchanged after sternotomy (T2 v T3: -24.35 [IQR -20.63 to -29.88] v -23.75 [IQR -20.25 to -29.28]; not significant) but deteriorated significantly after CABG (T1 v T4: -22.35 [IQR -17.70 to -27.22] v -18.5 [IQR -16.90 to -21.65]; p = 0.004). CONCLUSION: In patients undergoing on-pump CABG, 3D-RV FWS values for awake, spontaneously breathing patients measured with TTE and values assessed in patients under general anesthesia with TEE did not significantly differ. Three-dimensional RV FWS did not change after sternotomy but deteriorated after on-pump CABG.