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Dopamine Oppositely Modulates State Transitions in Striosome and Matrix Direct Pathway Striatal Spiny Neurons
Journal article   Open access   Peer reviewed

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

Eric M. Prager, Daniel B. Dorman, Zachary B. Hobel, Jeffrey M. Malgady, Kim T. Blackwell and Joshua L. Plotkin
Neuron (Cambridge, Mass.), Vol.108(6), pp.1091-1102.e5
12/23/2020
DOI: 10.1016/j.neuron.2020.09.028
PMCID: 7769890
PMID: 33080228
url
https://doi.org/10.1016/j.neuron.2020.09.028View
Published (Version of record) Open Access

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. [Display omitted] •Both striosome and matrix dSPNs support dendritically evoked somatic “up-states”•Dopamine oppositely modulates up-state length in striosome versus matrix dSPNs via D1Rs•Compartment-specific responses to D1R activation involve L-type Ca2+ channels•Changes in striatal dopamine may shift the balance of striosome versus matrix output Prager et al. show that dopamine promotes the maintenance of dendritically evoked “up-states” in mouse direct pathway matrix SPNs but opposes it in striosomes. This requires postsynaptic D1 receptors and involves differential engagement of L-type Ca2+ channels. These findings reveal a mechanism where fluctuations in dopamine may constrain compartment-specific striatal output.
2-photon imaging dendrite L-type calcium channel model plateau state-transition striatum synaptic integration up-state voltage-gated calcium channel

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