Gene expression profiling of inputs to the mesolimbic dopamine circuit
Ontology highlight
ABSTRACT:
ORGANISM(S): Mus musculus
PROVIDER: GSE95234 | GEO | 2017/03/20
SECONDARY ACCESSION(S): PRJNA376454
REPOSITORIES: GEO
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Project description:Gene expression profiling of inputs to the mesolimbic dopamine circuit
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Project description:Unified visual perception relies on the integration of bottom-up and top-down inputs in the primary visual cortex (V1), with top-down inputs known to provide behavior-related modulation on visual processing. However, the organization of top-down inputs in V1 remains unclear. Here, using optogenetics-assisted circuit mapping, we characterized how multiple top-down inputs from higher-order cortical and thalamic areas engage excitatory and inhibitory neurons in V1. Systematic layer- and cell-type-specific profiling of the innervation properties of top-down inputs ultimately revealed that each top-down input employs a unique laminar profile when innervating V1. These profiles partially overlap in superficial layers, bypass layer 4 (L4), and clearly segregate upon reaching deep layers. Specifically, inputs from the medial secondary visual cortex (V2M) and anterior cingulate cortex (ACA) preferentially activate L6 neurons, while inputs from the ventrolateral orbitofrontal cortex (ORBvl) and lateral posterior thalamic nucleus (LP) activate L5 neurons. Having defined the inputs, we conducted independent optogenetic activation studies and discovered that ORBvl and LP inputs selectively activate two types of pyramidal neurons (Pyrs) in L5: Pyr <-- ORBvl and Pyr <-- LP neurons, each with specific electrophysiological properties and gene expression profiles. Retrograde mapping subsequently revealed that Pyr <-- ORBvl neurons preferentially innervate subcortical areas and Pyr <-- LP neurons innervate cortical areas, indicating parallel processing of ORBvl and LP inputs in Pyr-type-specific subnetworks. Further, we found mutual inhibition between these two subnetworks, as LP inputs indirectly inhibit Pyr <-- ORBvl neurons and ORBvl inputs inhibit Pyr <-- LP neurons through local inhibitory neurons. Our study thus deepens understanding of the neuronal mechanisms involved in top-down modulation of visual processing by providing a valuable resource characterizing the layer- and cell-type-specific organization of top-down inputs in V1 and by revealing that L5 Pyr-type-specific subnetworks engage in parallel processing of corticocortical and thalamocortical top-down inputs.
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Project description:Astrocytes, the most abundant cells in the central nervous system, promote synapse formation and help refine neural connectivity. Although they are allocated to spatially distinct regional domains during development, it is unknown whether region-restricted astrocytes are functionally heterogeneous. Here we show that postnatal spinal cord astrocytes express several region-specific genes, and that ventral astrocyte-encoded Semaphorin3a (Sema3a) is required for proper motor neuron and sensory neuron circuit organization. Loss of astrocyte-encoded Sema3a led to dysregulated α−motor neuron axon initial segment orientation, markedly abnormal synaptic inputs, and selective death of α−but not of adjacent γ−motor neurons. Additionally, a subset of TrkA+ sensory afferents projected to ectopic ventral positions. These findings demonstrate that stable maintenance of a positional cue by developing astrocytes influences multiple aspects of sensorimotor circuit formation. More generally, they suggest that regional astrocyte heterogeneity may help to coordinate postnatal neural circuit refinement.
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