Effects Of Other Perturbations Research Articles

Interhemispheric dominance switching in a neural network model for birdsong.

Male zebra finches produce a sequence-invariant set of syllables, separated by short inspiratory gaps. These songs are learned from an adult tutor and maintained throughout life, making them a tractable model system for learned, sequentially ordered behaviors, particularly speech production. Moreover, much is known about the cortical, thalamic, and brain stem areas involved in producing this behavior, with the premotor cortical nucleus HVC (proper name) being of primary importance. In a previous study, our group developed a behavioral neural network model for birdsong constrained by the structural connectivity of the song system, the signaling properties of individual neurons and circuits, and circuit-breaking behavioral studies. Here we describe a more computationally tractable model and use it to explain the behavioral effects of unilateral cooling and electrical stimulations of HVC on song production. The model demonstrates that interhemispheric switching of song control is sufficient to explain these results, consistent with the hypotheses proposed when the experiments were initially conducted. Finally, we use the model to make testable predictions that can be used to validate the model framework and explain the effects of other perturbations of the song system, such as unilateral ablations of the primary input and output nuclei of HVC. NEW & NOTEWORTHY In this report, we propose a two-hemisphere neural network model for the bilaterally symmetrical song system underlying birdsong in the male zebra finch. This model captures the behavioral effects of unilateral cooling and electrical stimulations of the premotor cortical nucleus HVC during song production, supporting the hypothesis of interhemispheric switching of song control. We use the model to make testable predictions regarding the behavioral effects of other unilateral perturbations to the song system.

Population-Based Mathematical Modeling Facilitates the Interpretation of Dynamic Clamp Experiments in Cardiomyocytes

Dynamic clamp (DC) is a powerful method that comprehensively probes how the AP responds to perturbations based on different currents intrinsic to cardiomyocytes. In this closed-loop method, a current is calculated based on the time course of measured voltage, and a scaled version of the calculated current is applied to the cell in real-time. However, since DC currents differ from endogenous currents in several ways, care needs to be taken in interpreting results of these experiments. Since our experiments found significant between-cell heterogeneity in the response to DC perturbations, in order to guide appropriate understanding of these experiments we performed population-based simulations of DC perturbations with different assumptions that reflect how DC currents differ from endogenous currents.DC currents lack the ionic selectivity of endogenous currents. Simulations of DC perturbations with and without ionic selectivity showed that a lack of ionic selectivity leads to overestimation of the effect of the L-type calcium current on APD, but that the effects of other perturbations were largely unaffected. Furthermore, while endogenous currents respond directly to intracellular ionic concentrations, these values are unknown in experiments and must instead be estimated for the calculation of DC currents. We performed simulations where DC currents were calculated using either true ionic concentrations or estimates thereof, and while we found only minor differences in the mean perturbation effect sizes between these two paradigms, the patterns of variability in cell response across a population of models differed significantly, with the latter method producing a closer approximation of experimental results.By illustrating the strengths and shortcomings of how well dynamic clamp perturbations approximate changes in endogenous currents, these simulations allow for more accurate interpretation of dynamic clamp results.

A Jahn-Teller study of the orthorhombically distorted centre in and

centres in and are strongly coupled Jahn-Teller systems. A theoretical Jahn-Teller model is developed, in which the parameters that appear in the effective Hamiltonian describing the ground state of the ion are obtained by fitting previously published EPR results. It is found necessary to include certain random strains in the analysis in order to explain the orthorhombic features of the EPR spectra. The coupling between the ground and excited states and the effects of other perturbations are discussed.