Dataset Information

Dopamine Oppositely Modulates State Transitions in Striosome and Matrix Direct Pathway Striatal Spiny Neurons.

ABSTRACT: Corticostriatal synaptic integration is partitioned among striosome (patch) and matrix compartments of the dorsal striatum, allowing compartmentalized control of discrete aspects of behavior. Despite the significance of such organization, it's unclear how compartment-specific striatal output is dynamically achieved, particularly considering new evidence that overlap of afferents is substantial. We show that dopamine oppositely shapes responses to convergent excitatory inputs in mouse striosome and matrix striatal spiny projection neurons (SPNs). Activation of postsynaptic D1 dopamine receptors promoted the generation of long-lasting synaptically evoked "up-states" in matrix SPNs but opposed it in striosomes, which were more excitable under basal conditions. Differences in dopaminergic modulation were mediated, in part, by dendritic voltage-gated calcium channels (VGCCs): pharmacological manipulation of L-type VGCCs reversed compartment-specific responses to D1 receptor activation. These results support a novel mechanism for the selection of striatal circuit components, where fluctuating levels of dopamine shift the balance of compartment-specific striatal output.

SUBMITTER: Prager EM

PROVIDER: S-EPMC7769890 | biostudies-literature | 2020 Dec

REPOSITORIES: biostudies-literature

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Dopamine Oppositely Modulates State Transitions in Striosome and Matrix Direct Pathway Striatal Spiny Neurons.

Prager Eric M EM Dorman Daniel B DB Hobel Zachary B ZB Malgady Jeffrey M JM Blackwell Kim T KT Plotkin Joshua L JL

Neuron 20201019 6

Corticostriatal synaptic integration is partitioned among striosome (patch) and matrix compartments of the dorsal striatum, allowing compartmentalized control of discrete aspects of behavior. Despite the significance of such organization, it's unclear how compartment-specific striatal output is dynamically achieved, particularly considering new evidence that overlap of afferents is substantial. We show that dopamine oppositely shapes responses to convergent excitatory inputs in mouse striosome a ...[more]

PMID: 33080228

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Project description:Many neurological disorders and diseases including drug addiction are associated with specific neuronal cell types in the brain. The striatum, a region that plays a critically important role in the development of addictive drug-related behavior, provides a good example of the cellular heterogeneity challenges associated with analyses of specific neuronal cell types. Such studies are needed to identify the adaptive changes in neuroproteomic signaling that occur in response to diseases such as addiction. The striatum contains two major cell types, D1 and D2 type dopaminoceptive medium spiny neurons (MSNs), whose cell bodies and processes are intermingled throughout this region. Since little is known about the proteomes of these two neuronal cell populations, we have begun to address this challenge by using fluorescence-activated nuclear sorting (FANS) to isolate nuclei-containing fractions from striatum from D1 and D2 "Translating Ribosome Affinity Purification" (TRAP) mice. This approach enabled us to devise and implement a robust and reproducible workflow for preparing samples from specific MSN cell types for mass spectrometry analyses. These analyses quantified at least 685 proteins in each of four biological replicates of 50 K sorted nuclei from two D1 mice/replicate and from each of four biological replicates of 50 K sorted nuclei from two D2 mice/replicate. Proteome analyses identified 87 proteins that were differentially expressed in D1 versus D2 MSN nuclei and principal component analysis (PCA) of these proteins separated the 8 biological replicates into specific cell types. Central network analysis of the 87 differentially expressed proteins identified Hnrnpd and Hnmpa2b1 in D1 and Cct2 and Cct7 in D2 as potential central interactors. This workflow can now be used to improve our understanding of many neurological diseases including characterizing the short and long-term impact of drugs of abuse on the proteomes of these two dopaminoceptive neuronal populations.

Dataset Information

Dopamine Oppositely Modulates State Transitions in Striosome and Matrix Direct Pathway Striatal Spiny Neurons.

Publications

Dopamine Oppositely Modulates State Transitions in Striosome and Matrix Direct Pathway Striatal Spiny Neurons.

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