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A theory of rate coding control by intrinsic plasticity effects.

ABSTRACT: Intrinsic plasticity (IP) is a ubiquitous activity-dependent process regulating neuronal excitability and a cellular correlate of behavioral learning and neuronal homeostasis. Because IP is induced rapidly and maintained long-term, it likely represents a major determinant of adaptive collective neuronal dynamics. However, assessing the exact impact of IP has remained elusive. Indeed, it is extremely difficult disentangling the complex non-linear interaction between IP effects, by which conductance changes alter neuronal activity, and IP rules, whereby activity modifies conductance via signaling pathways. Moreover, the two major IP effects on firing rate, threshold and gain modulation, remain unknown in their very mechanisms. Here, using extensive simulations and sensitivity analysis of Hodgkin-Huxley models, we show that threshold and gain modulation are accounted for by maximal conductance plasticity of conductance that situate in two separate domains of the parameter space corresponding to sub- and supra-threshold conductance (i.e. activating below or above the spike onset threshold potential). Analyzing equivalent integrate-and-fire models, we provide formal expressions of sensitivities relating to conductance parameters, unraveling unprecedented mechanisms governing IP effects. Our results generalize to the IP of other conductance parameters and allow strong inference for calcium-gated conductance, yielding a general picture that accounts for a large repertoire of experimental observations. The expressions we provide can be combined with IP rules in rate or spiking models, offering a general framework to systematically assess the computational consequences of IP of pharmacologically identified conductance with both fine grain description and mathematical tractability. We provide an example of such IP loop model addressing the important issue of the homeostatic regulation of spontaneous discharge. Because we do not formulate any assumptions on modification rules, the present theory is also relevant to other neural processes involving excitability changes, such as neuromodulation, development, aging and neural disorders.

SUBMITTER: Naude J

PROVIDER: S-EPMC3261921 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:Change in breeding phenology is often a response to environmental forcing, but less is known of the mechanism underlying such changes and their fitness consequences. Here, we report on changes in the breeding phenology from a 27-year longitudinal study (1991-2017) of individually marked, known-aged grey seals (Halichoerus grypus) on Sable Island, Nova Scotia, Canada. We used generalized linear mixed models and a 3-step process to develop a model that includes interactions between intrinsic and extrinsic covariates and to test hypotheses about the influence of fixed factors (maternal age, parity, previous reproductive success, pup sex, colony density, Atlantic Multidecal Oscillation (AMO), North Atlantic Oscillation (NAO), and Sea Surface Temperature) and a random factor (female identity) on parturition dates. We also examined the consequences of the shift in birthdates on maternal energy allocation in offspring as measured by pup weaning mass. Birthdates were known for 2,768 pups of 660 known-age females. For 494 females with ≥2 parturition dates, repeatability as measured by the intraclass correlation was high (mean = 0.66). 87% of the variation in birthdates was explained by a mixed-effects model that included intrinsic and extrinsic fixed effects. Most of the explained variation was associated with the random effect of female identity. Parity was the most important intrinsic fixed effect, with inexperienced mothers giving birth later in the season than multiparous females. Over almost 3 decades, mean birthdates advanced by 15 days. The mixed model with intrinsic effects and population size, the detrended AMO from the previous year and mean NAO in the previous 3 years explained 80% of the variation with 21% of variation from the fixed effects. Both primiparous and multiparous individuals responded to the climate forcing, and there was strong evidence for heterogeneity in the response. Nevertheless, the shift in birthdates did not impact pup weaning mass.

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A theory of rate coding control by intrinsic plasticity effects.

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