Dataset Information

Molecular Logic of Spinocerebellar Tract Neuron Diversity and Connectivity.

ABSTRACT: Coordinated motor behaviors depend on feedback communication between peripheral sensory systems and central circuits in the brain and spinal cord. Relay of muscle- and tendon-derived sensory information to the CNS is facilitated by functionally and anatomically diverse groups of spinocerebellar tract neurons (SCTNs), but the molecular logic by which SCTN diversity and connectivity is achieved is poorly understood. We used single-cell RNA sequencing and genetic manipulations to define the mechanisms governing the molecular profile and organization of SCTN subtypes. We found that SCTNs relaying proprioceptive sensory information from limb and axial muscles are generated through segmentally restricted actions of specific Hox genes. Loss of Hox function disrupts SCTN-subtype-specific transcriptional programs, leading to defects in the connections between proprioceptive sensory neurons, SCTNs, and the cerebellum. These results indicate that Hox-dependent genetic programs play essential roles in the assembly of neural circuits necessary for communication between the brain and spinal cord.

SUBMITTER: Baek M

PROVIDER: S-EPMC6555431 | biostudies-literature | 2019 May

REPOSITORIES: biostudies-literature

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Molecular Logic of Spinocerebellar Tract Neuron Diversity and Connectivity.

Baek Myungin M Menon Vilas V Jessell Thomas M TM Hantman Adam W AW Dasen Jeremy S JS

Cell reports 20190501 9

Coordinated motor behaviors depend on feedback communication between peripheral sensory systems and central circuits in the brain and spinal cord. Relay of muscle- and tendon-derived sensory information to the CNS is facilitated by functionally and anatomically diverse groups of spinocerebellar tract neurons (SCTNs), but the molecular logic by which SCTN diversity and connectivity is achieved is poorly understood. We used single-cell RNA sequencing and genetic manipulations to define the mechani ...[more]

PMID: 31141687

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Project description:Decades of research have revealed the remarkable complexity of the midbrain dopamine (DA) system, which comprises cells principally located in the ventral tegmental area (VTA) and substantia nigra pars compacta (SNc). Neither homogenous nor serving a singular function, the midbrain DA system is instead composed of distinct cell populations that (1) receive different sets of inputs, (2) project to separate forebrain sites, and (3) are characterized by unique transcriptional and physiological signatures. To appreciate how these differences relate to circuit function, we first need to understand the anatomical connectivity of unique DA pathways and how this connectivity relates to DA-dependent motivated behavior. We and others have provided detailed maps of the input-output relationships of several subpopulations of midbrain DA cells and explored the roles of these different cell populations in directing behavioral output. In this study, we analyze VTA inputs and outputs as a high dimensional dataset (10 outputs, 22 inputs), deploying computational techniques well-suited to finding interpretable patterns in such data. In addition to reinforcing our previous conclusion that the connectivity in the VTA is dependent on spatial organization, our analysis also uncovered a set of inputs elevated onto each projection-defined VTADA cell type. For example, VTADA→NAcLat cells receive preferential innervation from inputs in the basal ganglia, while VTADA→Amygdala cells preferentially receive inputs from populations sending a distributed input across the VTA, which happen to be regions associated with the brain's stress circuitry. In addition, VTADA→NAcMed cells receive ventromedially biased inputs including from the preoptic area, ventral pallidum, and laterodorsal tegmentum, while VTADA→mPFC cells are defined by dominant inputs from the habenula and dorsal raphe. We also go on to show that the biased input logic to the VTADA cells can be recapitulated using projection architecture in the ventral midbrain, reinforcing our finding that most input differences identified using rabies-based (RABV) circuit mapping reflect projection archetypes within the VTA.

Dataset Information

Molecular Logic of Spinocerebellar Tract Neuron Diversity and Connectivity.

Publications

Molecular Logic of Spinocerebellar Tract Neuron Diversity and Connectivity.

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