Biology subjects

Plotkin, J.

Publications and source records attributed to Plotkin, J..

4 recordsLinked to original sources

bioRxiv2026

LSD persistently disrupts affective pain processing

Psychedelics produce long-lasting effects, but their circuit mechanisms remain unclear. Here we show that, in rats, a single dose of lysergic acid diethylamide (LSD) persistently reduces pain affect. This effect is recapitulated by local administration in the anterior cingulate cortex (ACC), but not primary somatosensory cortex. Neuropixels recordings reveal that LSD suppresses stimulus-evoked nociceptive responses in the ACC, reducing the encoding of aversive value. Despite increasing intrinsic excitability ex vivo, LSD reduces the maximum stimulus-evoked firing of ACC neurons in vivo, indicating a dissociation between excitability and sensory encoding. Together, these findings show that psychedelics disrupt the cortical transformation of nociceptive input into aversive representations.

neuroscience↗

bioRxiv2018

Evolutionary games with environmental feedbacks

Strategic interactions form the basis for evolutionary game theory and often occur in dynamic environments. The various strategies employed in a population may alter the quality or state of the environment, which may in turn feedback to change the incentive structure of strategic interactions. This type of feedback is common in social-ecological systems, evolutionary-ecological systems, and even psychological-economic systems - where the state of the environment alters the dynamics of competing types, and vice versa. Here we develop a framework of \"eco-evolutionary game theory\" that permits the study of joint strategic and environmental dynamics, with feedbacks. We consider environments governed either by a renewable resource (e.g. common-pool harvesting) or a decaying resource (e.g. pollution byproducts). We show that the dynamics of strategies and the environment depend, crucially, on the incentives for individuals to lead or follow behavioral changes, and on the relative speed of environmental versus strategic change. Our analysis unites dynamical phenomena that occur in settings as diverse as human decision-making, plant nutrient acquisition, and resource harvesting. We discuss the implication of our results for fields ranging from ecology to economics.

evolutionary biology↗

bioRxiv2018

Inferring the shape of global epistasis

Genotype-phenotype relationships are notoriously complicated. Idiosyncratic interactions between specific combinations of mutations occur, and are difficult to predict. Yet it is increasingly clear that many interactions can be understood in terms of global epistasis. That is, mutations may act additively on some underlying, unobserved trait, and this trait is then transformed via a nonlinear function to the observed phenotype as a result of subsequent biophysical and cellular processes. Here we infer the shape of such global epistasis in three proteins, based on published high-throughput mutagenesis data. To do so, we develop a maximum-likelihood inference procedure using a flexible family of monotonic nonlinear functions spanned by an I-spline basis. Our analysis uncovers dramatic nonlinearities in all three proteins; in some proteins a model with global epistasis accounts for virtually all the measured variation, whereas in others we find substantial local epistasis as well. This method allows us to test hypotheses about the form of global epistasis and to distinguish variance components attributable to global epistasis, local epistasis, and measurement error.

evolutionary biology↗

bioRxiv2016

Phenotypic plasticity promotes recombination and gene clustering in periodic environments

The impact of changing environments on the evolution of genetic recombination is still unclear. While the Red Queen hypothesis provides a reasonable explanation for recombination, it requires coevolution with antagonistic species, such as host-parasite systems. We present a novel scenario for the evolution of recombination in changing environments: the genomic storage effect due to phenotypic plasticity. Using an analytic approximation and Monte Carlo simulations, we demonstrate that recombination evolves between a target locus that determines fitness, and a modifier locus that modulates the effects of alleles at the target. Evolution of recombination by this plasticity effect does not require antagonistic inter-specific interactions and, unlike in previous models, it occurs when only one target locus codes for a trait under selection. Furthermore, if the effects of multiple target loci are modified by the same plasticity locus, then the recombination rate among the target loci will tend to decrease, clustering the loci that influence a trait. These results provide a novel scenario for the evolution of recombination, highlighting the importance of phenotypic plasticity for recombination modification.

evolutionary biology↗