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Cell-type-specific population dynamics of diverse reward computations.

Cell | 2022

Computational analysis of cellular activity has developed largely independently of modern transcriptomic cell typology, but integrating these approaches may be essential for full insight into cellular-level mechanisms underlying brain function and dysfunction. Applying this approach to the habenula (a structure with diverse, intermingled molecular, anatomical, and computational features), we identified encoding of reward-predictive cues and reward outcomes in distinct genetically defined neural populations, including TH+ cells and Tac1+ cells. Data from genetically targeted recordings were used to train an optimized nonlinear dynamical systems model and revealed activity dynamics consistent with a line attractor. High-density, cell-type-specific electrophysiological recordings and optogenetic perturbation provided supporting evidence for this model. Reverse-engineering predicted how Tac1+ cells might integrate reward history, which was complemented by in vivo experimentation. This integrated approach describes a process by which data-driven computational models of population activity can generate and frame actionable hypotheses for cell-type-specific investigation in biological systems.

Pubmed ID: 36113428 RIS Download

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This is a list of tools and resources that we have found mentioned in this publication.


NEURON (tool)

RRID:SCR_005393

NEURON is a simulation environment for modeling individual neurons and networks of neurons. It provides tools for conveniently building, managing, and using models in a way that is numerically sound and computationally efficient. It is particularly well-suited to problems that are closely linked to experimental data, especially those that involve cells with complex anatomical and biophysical properties. NEURON has benefited from judicious revision and selective enhancement, guided by feedback from the growing number of neuroscientists who have used it to incorporate empirically-based modeling into their research strategies. NEURON's computational engine employs special algorithms that achieve high efficiency by exploiting the structure of the equations that describe neuronal properties. It has functions that are tailored for conveniently controlling simulations, and presenting the results of real neurophysiological problems graphically in ways that are quickly and intuitively grasped. Instead of forcing users to reformulate their conceptual models to fit the requirements of a general purpose simulator, NEURON is designed to let them deal directly with familiar neuroscience concepts. Consequently, users can think in terms of the biophysical properties of membrane and cytoplasm, the branched architecture of neurons, and the effects of synaptic communication between cells. * helps users focus on important biological issues rather than purely computational concerns * has a convenient user interface * has a user-extendable library of biophysical mechanisms * has many enhancements for efficient network modeling * offers customizable initialization and simulation flow control * is widely used in neuroscience research by experimentalists and theoreticians * is well-documented and actively supported * is free, open source, and runs on (almost) everything

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Synapse (tool)

RRID:SCR_006307

A cloud-based collaborative platform which co-locates data, code, and computing resources for analyzing genome-scale data and seamlessly integrates these services allowing scientists to share and analyze data together. Synapse consists of a web portal integrated with the R/Bioconductor statistical package and will be integrated with additional tools. The web portal is organized around the concept of a Project which is an environment where you can interact, share data, and analysis methods with a specific group of users or broadly across open collaborations. Projects provide an organizational structure to interact with data, code and analyses, and to track data provenance. A project can be created by anyone with a Synapse account and can be shared among all Synapse users or restricted to a specific team. Public data projects include the Synapse Commons Repository (SCR) (syn150935) and the metaGenomics project (syn275039). The SCR provides access to raw data and phenotypic information for publicly available genomic data sets, such as GEO and TCGA. The metaGenomics project provides standardized preprocessed data and precomputed analysis of the public SCR data.

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Imaris (tool)

RRID:SCR_007370

Imaris provides range of capabilities for working with three dimensional images. Uses flexible editing and processing functions, such as interactive surface rendering and object slicing capabilities. And output to standard TIFF, Quicktime and AVI formats. Imaris accepts virtually all image formats that are used in confocal microscopy and many of those used in wide-field image acquisition.

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STOCK Tg(Chat-cre)GM24Gsat/Mmucd (organism)

RRID:MMRRC_017269-UCD

Mus musculus with name STOCK Tg(Chat-cre)GM24Gsat/Mmucd from MMRRC.

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C57BL/6J (organism)

RRID:IMSR_JAX:000664

Mus musculus with name C57BL/6J from IMSR.

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B6;129S-Tac1tm1.1(cre)Hze/J (organism)

RRID:IMSR_JAX:021877

Mus musculus with name B6;129S-Tac1tm1.1(cre)Hze/J from IMSR.

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B6.Cg-Calb1tm1.1(folA/cre)Hze/J (organism)

RRID:IMSR_JAX:023531

Mus musculus with name B6.Cg-Calb1tm1.1(folA/cre)Hze/J from IMSR.

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B6.129X1-Thtm1(cre)Te/Kieg (organism)

RRID:IMSR_EM:00254

Mus musculus with name B6.129X1-Thtm1(cre)Te/Kieg from IMSR.

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