Extracting non-linear integrate-and-fire models from experimental data using dynamic I–V curves

The dynamic I–V curve method was recently introduced for the efficient experimental generation of reduced neuron models. The method extracts the response properties of a neuron while it is subject to a naturalistic stimulus that mimics in vivo-like fluctuating synaptic drive. The resulting history-dependent, transmembrane current is then projected onto a one-dimensional current–voltage relation that provides the basis for a tractable non-linear integrate-and-fire model. An attractive feature of the method is that it can be used in spike-triggered mode to quantify the distinct patterns of post-spike refractoriness seen in different classes of cortical neuron. The method is first illustrated using a conductance-based model and is then applied experimentally to generate reduced models of cortical layer-5 pyramidal cells and interneurons, in injected-current and injected- conductance protocols. The resulting low-dimensional neuron models—of the refractory exponential integrate-and-fire type—provide highly accurate predictions for spike-times. The method therefore provides a useful tool for the construction of tractable models and rapid experimental classification of cortical neurons

Dynamic I-V curves are reliable predictors of naturalistic pyramidal-neuron voltage traces

Neuronal response properties are typically probed by intracellular measurements of current-voltage (I-V) relationships during application of current or voltage steps. Here we demonstrate the measurement of a novel I-V curve measured while the neuron exhibits a fluctuating voltage and emits spikes. This dynamic I-V curve requires only a few tens of seconds of experimental time and so lends itself readily to the rapid classification of cell type, quantification of heterogeneities in cell populations, and generation of reduced analytical models. We apply this technique to layer-5 pyramidal cells and show that their dynamic I-V curve comprises linear and exponential components, providing experimental evidence for a recently proposed theoretical model. The approach also allows us to determine the change of neuronal response properties after a spike, millisecond by millisecond, so that postspike refractoriness of pyramidal cells can be quantified. Observations of I-V curves during and in absence of refractoriness are cast into a model that is used to predict both the subthreshold response and spiking activity of the neuron to novel stimuli. The predictions of the resulting model are in excellent agreement with experimental data and close to the intrinsic neuronal reproducibility to repeated stimuli

CV events leading to hospitalization and CV interventions in the last 12 months (%).^*

<p>AF, atrial fibrillation; CABG, coronary artery bypass graft; CNS, central nervous system; CV, cardiovascular; HF, heart failure; PCI, percutaneous coronary intervention.</p>*<p>Data are not complete for all patients: the reported percentage is for the number of patients with data available for each given variable.</p><p><a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0086443#pone.0086443.s005" target="_blank">Table S5</a> shows CV events leading to hospitalization and CV interventions in the last 12 months for permanent AF patients according to revised definition of control used in the RACE II study, i.e., lenient control (in sinus rhythm or in AF with heart rate [HR] <110 beats per minute [bpm]) or no control (no sinus rhythm and in AF with HR ≥110 bpm).</p

Management strategy chosen for AF (%).^*

<p>AF, atrial fibrillation.</p><p>Rate (± rhythm): rate control with or without rhythm control; rhythm (± rate): rhythm control with or without rate control.</p>*<p>Data are not complete for all patients: the reported percentage is for the number of patients with data available for each given variable.</p>†<p>Including pharmacologic cardioversion with AAD therapy and electrical cardioversion; data are not complete for all patients: the reported percentage is for the number of patients with data available for each given variable.</p><p><a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0086443#pone.0086443.s006" target="_blank">Table S6</a> shows management strategy for permanent AF patients according to revised definition of control used in the RACE II study, i.e., lenient control (in sinus rhythm or in AF with heart rate [HR] <110 beats per minute [bpm]) or no control (no sinus rhythm and in AF with HR ≥110 bpm).</p

The SAGE study: global observational analysis of glycaemic control, hypoglycaemia and diabetes management in T1DM

International audienceAims: To describe glycaemic control and diabetes management in adults with type 1 diabetes (T1DM), in a real-life global setting.Materials and methods: Study of Adults' GlycEmia (SAGE) was a multinational, multicentre, single visit, non-interventional, cross-sectional study in adult patients with T1DM. Data were collected at a single visit, analysed according to predefined age groups (26-44, 45-64, and ≥65 years), and reported across different regions. The primary endpoint was the proportion of participants achieving HbA1c <7.0 % in each age group. Secondary endpoints included incidence of hypoglycaemia, severe hypoglycaemia and severe hyperglycaemia leading to diabetic ketoacidosis (DKA), and therapeutic management of T1DM.Results: Of 3903 included participants, 3858 (98.8%) were eligible for the study. Overall, 24.3% (95% confidence interval [CI]: 22.9 to 25.6) of participants achieved the glycaemic target of HbA1c <7.0 %, with more participants achieving this target in the 26-44 years group (27.6% [95% CI: 25.5 to 29.8]). Target achievement was highest in Eastern and Western Europe, and lowest in the Middle East. The incidence of hypoglycaemia and of severe hyperglycaemia leading to DKA tended to decrease with age, and varied across regions. Age and regional differences were observed in therapeutic management, including types of device/insulin usage, frequency of insulin dose adjustment, and technology usage.Conclusions: Glycaemic control remains poor in adults with T1DM globally. Several areas of treatment may be optimised to improve outcomes, including supporting patient self-management of insulin therapy, increasing use of technologies such as CGM, and greater provision of healthcare support. This article is protected by copyright. All rights reserved

Multivariate logistic regression analysis: independent predictors for choice of management strategy at the end of the visit (rhythm-control strategy vs. rate-control strategy).

<p>AF, atrial fibrillation; BMI, body mass index; bpm, beats per minute; CI, confidence interval; EHRA, European Heart Rhythm Association; HF, heart failure; HR, heart rhythm; OR, odds ratio.</p

(A) AF control (at visit) and (B) AF symptoms (EHRA) (at visit) according to AF management strategy prior to the visit.

<p>p<0.001 (AF control); p<0.001 (AF symptoms). AF, atrial fibrillation; bpm, beats per minute; EHRA, European Heart Rhythm Association.</p