Dataset Information

Synthetic circuit for exact adaptation and fold-change detection.

ABSTRACT: Biological organisms use their sensory systems to detect changes in their environment. The ability of sensory systems to adapt to static inputs allows wide dynamic range as well as sensitivity to input changes including fold-change detection, a response that depends only on fold changes in input, and not on absolute changes. This input scale invariance underlies an important strategy for search that depends solely on the spatial profile of the input. Synthetic efforts to reproduce the architecture and response of cellular circuits provide an important step to foster understanding at the molecular level. We report the bottom-up assembly of biochemical systems that show exact adaptation and fold-change detection. Using a malachite green aptamer as the output, a synthetic transcriptional circuit with the connectivity of an incoherent feed-forward loop motif exhibits pulse generation and exact adaptation. A simple mathematical model was used to assess the amplitude and duration of pulse response as well as the parameter regimes required for fold-change detection. Upon parameter tuning, this synthetic circuit exhibits fold-change detection for four successive rounds of two-fold input changes. The experimental realization of fold-change detection circuit highlights the programmability of transcriptional switches and the ability to obtain predictive dynamical systems in a cell-free environment for technological applications.

SUBMITTER: Kim J

PROVIDER: S-EPMC4027175 | biostudies-literature | 2014 May

REPOSITORIES: biostudies-literature

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Synthetic circuit for exact adaptation and fold-change detection.

Kim Jongmin J Khetarpal Ishan I Sen Shaunak S Murray Richard M RM

Nucleic acids research 20140411 9

Biological organisms use their sensory systems to detect changes in their environment. The ability of sensory systems to adapt to static inputs allows wide dynamic range as well as sensitivity to input changes including fold-change detection, a response that depends only on fold changes in input, and not on absolute changes. This input scale invariance underlies an important strategy for search that depends solely on the spatial profile of the input. Synthetic efforts to reproduce the architectu ...[more]

PMID: 24728988

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Project description:Visual processing transforms the complexities of the visual world into useful information. Ciona, an invertebrate chordate and close relative of the vertebrates, has one of the simplest nervous systems known, yet has a range of visuomotor behaviors. This simplicity has facilitated studies linking behavior and neural circuitry. Ciona larvae have two distinct visuomotor behaviors - a looming shadow response and negative phototaxis. These are mediated by separate neural circuits that initiate from different clusters of photoreceptors, with both projecting to a CNS structure called the posterior brain vesicle (pBV). We report here that inputs from both circuits are processed to generate fold change detection (FCD) outputs. In FCD, the behavioral response scales with the relative fold change in input, but is invariant to the overall magnitude of the stimulus. Moreover, the two visuomotor behaviors have fundamentally different stimulus/response relationships - indicative of differing circuit strategies, with the looming shadow response showing a power relationship to fold change, while the navigation behavior responds linearly. Pharmacological modulation of the FCD response points to the FCD circuits lying outside of the visual organ (the ocellus), with the pBV being the most likely location. Consistent with these observations, the connectivity and properties of pBV interneurons conform to known FCD circuit motifs, but with different circuit architectures for the two circuits. The negative phototaxis circuit forms a putative incoherent feedforward loop that involves interconnecting cholinergic and GABAergic interneurons. The looming shadow circuit uses the same cholinergic and GABAergic interneurons, but with different synaptic inputs to create a putative non-linear integral feedback loop. These differing circuit architectures are consistent with the behavioral outputs of the two circuits. Finally, while some reports have highlighted parallels between the pBV and the vertebrate midbrain, suggesting a common origin for the two, others reports have disputed this, suggesting that invertebrate chordates lack a midbrain homolog. The convergence of visual inputs at the pBV, and its putative role in visual processing reported here and in previous publications, lends further support to the proposed common origin of the pBV and the vertebrate midbrain.

Dataset Information

Synthetic circuit for exact adaptation and fold-change detection.

Publications

Synthetic circuit for exact adaptation and fold-change detection.

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