Neurons show diverse firing patterns. Even neurons belonging to a single chemical or morphological class, or the same identified neuron, can display different types of electrical activity. For example, motor neuron MN5, which innervates a flight muscle of adult Drosophila, can show distinct firing patterns under the same recording conditions. We developed a two-dimensional biophysical model and show that a core complement of just two voltage-gated channels is sufficient to generate firing pattern diversity. We propose Shab and DmNa v to be two candidate genes that could encode these core currents, and find that changes in Shab channel expression in the model can reproduce activity resembling the main firing patterns observed in MN5 recordings. We use bifurcation analysis to describe the different transitions between rest and spiking states that result from variations in Shab channel expression, exposing a connection between ion channel expression, bifurcation structure, and firing patterns in models of membrane potential dynamics.

Neural representations of odors are subject to computations that involve sequentially convergent and divergent anatomical connections across different areas of the brains in both mammals and insects. Furthermore, in both mammals and insects higher order brain areas are connected via feedback connections. In order to understand the transformations and interactions that this connectivity make possible, an ideal experiment would compare neural responses across different, sequential processing levels. Here we present results of recordings from a first order olfactory neuropile – the antennal lobe (AL) – and a higher order multimodal integration and learning center – the mushroom body (MB) – in the honey bee brain. We recorded projection neurons (PN) of the AL and extrinsic neurons (EN) of the MB, which provide the outputs from the two neuropils. Recordings at each level were made in different animals in some experiments and simultaneously in the same animal in others. We presented two odors and their mixture to compare odor response dynamics as well as classification speed and accuracy at each neural processing level. Surprisingly, the EN ensemble significantly starts separating odor stimuli rapidly and before the PN ensemble has reached significant separation. Furthermore the EN ensemble at the MB output reaches a maximum separation of odors between 84–120 ms after odor onset, which is 26 to 133 ms faster than the maximum separation at the AL output ensemble two synapses earlier in processing. It is likely that a subset of very fast PNs, which respond before the ENs, may initiate the rapid EN ensemble response. We suggest therefore that the timing of the EN ensemble activity would allow retroactive integration of its signal into the ongoing computation of the AL via centrifugal feedback.

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Electrical signaling allows communication within and between different tissues and is necessary for the survival of multicellular organisms. The ionic transport that underlies transmembrane currents in cells is mediated by transporters and channels. Fast ionic transport through channels is typically modeled with a conductance-based formulation that describes current in terms of electrical drift without diffusion. In contrast, currents written in terms of drift and diffusion are not as widely used in the literature in spite of being more realistic and capable of displaying experimentally observable phenomena that conductance-based models cannot reproduce (e.g. rectification). The two formulations are mathematically related: conductance-based currents are linear approximations of drift-diffusion currents. However, conductance-based models of membrane potential are not first-order approximations of drift-diffusion models. Bifurcation analysis and numerical simulations show that the two approaches predict qualitatively and quantitatively different behaviors in the dynamics of membrane potential. For instance, two neuronal membrane models with identical populations of ion channels, one written with conductance-based currents, the other with drift-diffusion currents, undergo transitions into and out of repetitive oscillations through different mechanisms and for different levels of stimulation. These differences in excitability are observed in response to excitatory synaptic input, and across different levels of ion channel expression. In general, the electrophysiological profiles of membranes modeled with drift-diffusion and conductance-based models having identical ion channel populations are different, potentially causing the input-output and computational properties of networks constructed with these models to be different as well. The drift-diffusion formulation is thus proposed as a theoretical improvement over conductance-based models that may lead to more accurate predictions and interpretations of experimental data at the single cell and network levels.

A general formulation for both passive and active transmembrane transport is derived from basic thermodynamical principles. The derivation takes into account the energy required for the motion of molecules across membranes, and includes the possibility of modeling asymmetric flow. Transmembrane currents can then be described by the general model in the case of electrogenic flow. As it is desirable in new models, it is possible to derive other well known expressions for transmembrane currents as particular cases of the general formulation. For instance, the conductance-based formulation for current turns out to be a linear approximation of the general formula for current. Also, under suitable assumptions, other formulas for current based on electrodiffusion, like the constant field approximation by Goldman, can also be recovered from the general formulation. The applicability of the general formulations is illustrated first with fits to existing data, and after, with models of transmembrane potential dynamics for pacemaking cardiocytes and neurons. The general formulations presented here provide a common ground for the biophysical study of physiological phenomena that depend on transmembrane transport.

BackgroundInfluenza viruses are a major cause of morbidity and mortality worldwide. Vaccination remains a powerful tool for preventing or mitigating influenza outbreaks. Yet, vaccine supplies and daily administration capacities are limited, even in developed countries. Understanding how such constraints can alter the mitigating effects of vaccination is a crucial part of influenza preparedness plans. Mathematical models provide tools for government and medical officials to assess the impact of different vaccination strategies and plan accordingly. However, many existing models of vaccination employ several questionable assumptions, including a rate of vaccination proportional to the population at each point in time.MethodsWe present a SIR-like model that explicitly takes into account vaccine supply and the number of vaccines administered per day and places data-informed limits on these parameters. We refer to this as the non-proportional model of vaccination and compare it to the proportional scheme typically found in the literature.ResultsThe proportional and non-proportional models behave similarly for a few different vaccination scenarios. However, there are parameter regimes involving the vaccination campaign duration and daily supply limit for which the non-proportional model predicts smaller epidemics that peak later, but may last longer, than those of the proportional model. We also use the non-proportional model to predict the mitigating effects of variably timed vaccination campaigns for different levels of vaccination coverage, using specific constraints on daily administration capacity.ConclusionsThe non-proportional model of vaccination is a theoretical improvement that provides more accurate predictions of the mitigating effects of vaccination on influenza outbreaks than the proportional model. In addition, parameters such as vaccine supply and daily administration limit can be easily adjusted to simulate conditions in developed and developing nations with a wide variety of financial and medical resources. Finally, the model can be used by government and medical officials to create customized pandemic preparedness plans based on the supply and administration constraints of specific communities.

IntroductionMathematical models and field data suggest that human mobility is an important driver for Dengue virus transmission. Nonetheless little is known on this matter due the lack of instruments for precise mobility quantification and study design difficulties.Materials and methodsWe carried out a cohort-nested, case-control study with 126 individuals (42 cases, 42 intradomestic controls and 42 population controls) with the goal of describing human mobility patterns of recently Dengue virus-infected subjects, and comparing them with those of non-infected subjects living in an urban endemic locality. Mobility was quantified using a GPS-data logger registering waypoints at 60-second intervals for a minimum of 15 natural days.ResultsAlthough absolute displacement was highly biased towards the intradomestic and peridomestic areas, occasional displacements exceeding a 100-Km radius from the center of the studied locality were recorded for all three study groups and individual displacements were recorded traveling across six states from central Mexico. Additionally, cases had a larger number of visits out of the municipality´s administrative limits when compared to intradomestic controls (cases: 10.4 versus intradomestic controls: 2.9, p = 0.0282). We were able to identify extradomestic places within and out of the locality that were independently visited by apparently non-related infected subjects, consistent with houses, working and leisure places.ConclusionsResults of this study show that human mobility in a small urban setting exceeded that considered by local health authority’s administrative limits, and was different between recently infected and non-infected subjects living in the same household. These observations provide important insights about the role that human mobility may have in Dengue virus transmission and persistence across endemic geographic areas that need to be taken into account when planning preventive and control measures. Finally, these results are a valuable reference when setting the parameters for future mathematical modeling studies.

Acute dopamine receptor blockade in substantia nigra pars reticulata: a possible model for drug-induced Parkinsonism. Dopamine (DA) depletion modifies the firing pattern of neurons in the substantia nigra pars reticulata (SNr), shifting their mostly tonic firing toward irregularity and bursting, traits of pathological firing underlying rigidity and postural instability in Parkinson's disease (PD) patients and animal models of Parkinsonism (PS). Drug-induced Parkinsonism (DIP) represents 20 -40% of clinical cases of PS, becoming a problem for differential diagnosis, and is still not well studied with physiological tools. It may co-occur with tardive dyskinesia. Here we use in vitro slice preparations including the SNr to observe drug-induced pathological firing by using drugs that most likely produce it, DA-receptor antagonists (SCH23390 plus sulpiride), to compare with firing patterns found in DA-depleted tissue. The hypothesis is that SNr firing would be similar under both conditions, a prerequisite to the proposal of a similar preparation to test other DIP-producing drugs. Firing was analyzed with three complementary metrics, showing similarities between DA depletion and acute DAreceptor blockade. Moreover, blockade of either nonselective cationic channels or Ca v 3 T-type calcium channels hyperpolarized the membrane and abolished bursting and irregular firing, silencing SNr neurons in both conditions. Therefore, currents generating firing in control conditions are in part responsible for pathological firing. Haloperidol, a DIP-producing drug, reproduced DA-receptor antagonist firing modifications. Since acute DA-receptor blockade induces SNr neuron firing similar to that found in the 6-hydroxydopamine model of PS, output basal ganglia neurons may play a role in generating DIP. Therefore, this study opens the way to test other DIP-producing drugs.NEW & NOTEWORTHY Dopamine (DA) depletion enhances substantia nigra pars reticulata (SNr) neuron bursting and irregular firing, hallmarks of Parkinsonism. Several drugs, including antipsychotics, antidepressants, and calcium channel antagonists, among others, produce drug-induced Parkinsonism. Here we show the first comparison between SNr neuron firing after DA depletion vs. firing found after acute blockade of DA receptors. It was found that firing in both conditions is similar, implying that pathological SNr neuron firing is also a physiological correlate of drug-induced Parkinsonism.