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Distinct mechanisms of CB1 and GABAB receptor presynaptic modulation of striatal indirect pathway projections to mouse globus pallidus

Sitzia, Giacomo ; Abrahao, Karina Possa ; Liput, Daniel ; Calandra, Gian Marco ; Lovinger, David M.

The Journal of physiology, 2023-01, Vol.601 (1), p.195-209 [Periódico revisado por pares]

London: Wiley Subscription Services, Inc

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  • Título:
    Distinct mechanisms of CB1 and GABAB receptor presynaptic modulation of striatal indirect pathway projections to mouse globus pallidus
  • Autor: Sitzia, Giacomo ; Abrahao, Karina Possa ; Liput, Daniel ; Calandra, Gian Marco ; Lovinger, David M.
  • Assuntos: basal ganglia ; Calcium channels ; Calcium channels (voltage-gated) ; calcium imaging ; Cannabinoid CB1 receptors ; Globus pallidus ; Medicin och hälsovetenskap ; Neostriatum ; Neuroscience ; neurotransmitter release ; optogenetics ; presynaptic ; Receptor mechanisms ; Synaptic transmission ; γ-Aminobutyric acid B receptors
  • É parte de: The Journal of physiology, 2023-01, Vol.601 (1), p.195-209
  • Notas: The peer review history is available in the Supporting Information section of this article
    This article was first published as a preprint. Sitzia G, Abrahao KP, Liput D, Calandra GM, Lovinger DM. 2022. Distinct mechanisms of CB1 and GABAB receptor presynaptic modulation of striatal indirect pathway projections to mouse Globus Pallidus. bioRxiv.
    https://doi.org/10.1113/JP283614#support‐information‐section
    https://doi.org/10.1101/2022.07.21.500979
    Handling Editors: David Wyllie & Ilan Lampl
    .
    ObjectType-Article-1
    SourceType-Scholarly Journals-1
    ObjectType-Feature-2
    content type line 23
    This article was first published as a preprint. Sitzia G, Abrahao KP, Liput D, Calandra GM, Lovinger DM. 2022. Distinct mechanisms of CB1 and GABAB receptor presynaptic modulation of striatal indirect pathway projections to mouse Globus Pallidus. bioRxiv. https://doi.org/10.1101/2022.07.21.500979
    The peer review history is available in the Supporting Information section of this article (https://doi.org/10.1113/JP283614#support‐information‐section).
  • Descrição: Presynaptic modulation is a fundamental process regulating synaptic transmission. Striatal indirect pathway projections originate from A2A‐expressing spiny projection neurons (iSPNs), targeting the globus pallidus external segment (GPe) and control the firing of the tonically active GPe neurons via GABA release. It is unclear if and how the presynaptic G‐protein‐coupled receptors (GPCRs), GABAB and CB1 receptors modulate iSPN‐GPe projections. Here we used an optogenetic platform to study presynaptic Ca2+ and GABAergic transmission at iSPN projections, using a genetic strategy to express the calcium sensor GCaMP6f or the excitatory channelrhodopsin (hChR2) on iSPNs. We found that P/Q‐type calcium channels are the primary voltage‐gated Ca2+ channel (VGCC) subtype controlling presynaptic calcium and GABA release at iSPN‐GPe projections. N‐type and L‐type VGCCs also contribute to GABA release at iSPN‐GPe synapses. GABAB receptor activation resulted in a reversible inhibition of presynaptic Ca2+ transients (PreCaTs) and an inhibition of GABAergic transmission at iSPN‐GPe synapses. CB1 receptor activation did not inhibit PreCaTs but inhibited GABAergic transmission at iSPN‐GPe projections. CB1 effects on GABAergic transmission persisted in experiments where NaV and KV1 were blocked, indicating a VGCC‐ and KV1‐independent presynaptic mechanism of action of CB1 receptors. Taken together, presynaptic modulation of iSPN‐GPe projections by CB1 and GABAB receptors is mediated by distinct mechanisms. Key points P/Q‐type are the predominant voltage‐gated Ca2+ channels controlling presynaptic Ca2+ and GABA release on the striatal indirect pathway projections. GABAB receptors modulate iSPN‐GPe projections via a VGCC‐dependent mechanism. CB1 receptors modulate iSPN‐GPe projections via a VGCC‐independent mechanism. figure legend Left: schematic diagram of the projection studied; the indirect pathway projection originating from striatal indirect pathway spiny projection neurons (iSPNs) and targeting the globus pallidus external segment (GPe). Right: proposed mechanism of action of GABAB and CB1 receptors on iSPN‐GPe projections. Presynaptic modulation of iSPN‐GPe projections by GABAB receptors is mediated by the inhibition of voltage‐gated Ca2+ channels (VGCCs). Presynaptic modulation of iSPN‐GPe projections by CB1 receptors is mediated by the inhibition of GABA release through a mechanism downstream of VGCCs.
  • Editor: London: Wiley Subscription Services, Inc
  • Idioma: Inglês
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