• Activation of Dopamine D1 Rece...

*Result*: Activation of Dopamine D1 Receptors at the Axon Initial Segment-Like Process of Retinal AII Amacrine Cells Modulates Action Potential Firing.

Title:
Activation of Dopamine D1 Receptors at the Axon Initial Segment-Like Process of Retinal AII Amacrine Cells Modulates Action Potential Firing.
Authors:
Veruki ML; Department of Biomedicine, University of Bergen, N-5009 Bergen, Norway margaret.veruki@uib.no espen.hartveit@uib.no.; Mohn Research Center for the Brain, University of Bergen, N-5009 Bergen, Norway., Liu JH; Department of Biomedicine, University of Bergen, N-5009 Bergen, Norway., Singh JB; Department of Biomedicine, University of Bergen, N-5009 Bergen, Norway., Luppi MS; Department of Biomedicine, University of Bergen, N-5009 Bergen, Norway.; Mohn Research Center for the Brain, University of Bergen, N-5009 Bergen, Norway., Hartveit E; Department of Biomedicine, University of Bergen, N-5009 Bergen, Norway margaret.veruki@uib.no espen.hartveit@uib.no.; Mohn Research Center for the Brain, University of Bergen, N-5009 Bergen, Norway.
Source:
The Journal of neuroscience : the official journal of the Society for Neuroscience [J Neurosci] 2025 Aug 13; Vol. 45 (33). Date of Electronic Publication: 2025 Aug 13.
Publication Type:
Journal Article
Language:
English
Journal Info:
Publisher: Society for Neuroscience Country of Publication: United States NLM ID: 8102140 Publication Model: Electronic Cited Medium: Internet ISSN: 1529-2401 (Electronic) Linking ISSN: 02706474 NLM ISO Abbreviation: J Neurosci Subsets: MEDLINE
Imprint Name(s):
Publication: Washington, DC : Society for Neuroscience
Original Publication: [Baltimore, Md.] : The Society, c1981-
MeSH Terms:
Receptors, Dopamine D1*/metabolism , Receptors, Dopamine D1*/agonists , Amacrine Cells*/physiology , Amacrine Cells*/drug effects , Amacrine Cells*/metabolism , Action Potentials*/physiology , Action Potentials*/drug effects , Retina*/cytology , Axon Initial Segment*/drug effects , Axon Initial Segment*/physiology , Axon Initial Segment*/metabolism, Dopamine Agonists/pharmacology ; Animals ; Rats ; Male ; Female
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Contributed Indexing:
Keywords: Nav1.1; ankyrin-G; axon initial segment; intrinsic excitability; neuromodulation; rod pathway
Substance Nomenclature:
0 (Receptors, Dopamine D1)
0 (Dopamine Agonists)
Entry Date(s):
Date Created: 20250709 Date Completed: 20250825 Latest Revision: 20260214
Update Code:
20260214
PubMed Central ID:
PMC12352536
DOI:
10.1523/JNEUROSCI.0736-25.2025
PMID:
40634127
Database:
MEDLINE

*Further Information*

*Dopamine is an important neuromodulator found throughout the central nervous system that can influence neural circuits involved in sensory, motor, and cognitive functions. In the retina, dopamine is released by specific amacrine cells and plays a role in reconfiguring circuits for photopic vision. This adaptation takes place both in photoreceptors and at postreceptoral sites. The AII amacrine cell, which plays a crucial role for transmission of both scotopic and photopic visual signals, has been considered an important target of dopaminergic modulation, expressed as a change in the strength of electrical coupling mediated by gap junctions between the AIIs. It has been difficult, however, to find clear evidence for expression of dopamine receptors by AII amacrines. Here, we combined injection of fluorescent dye in AIIs with immunolabeling of type 1 dopamine receptors (D1Rs) and made the surprising observation that D1Rs, along with KCNQ2, an M-type K<sup>+</sup> channel, are expressed at the AII axon initial segment-like process (AII-AIS) that also expresses voltage-gated Na<sup>+</sup> (Na<subscript>v</subscript>) channels and generates action potentials. With current-clamp recording of AIIs in rat (male, female) retinal slices, we found that D1R activation reduced spike frequency and increased spike threshold. Taken together with experiments using immunolabeling, pharmacological manipulation, and computational modeling, our results suggest that activation of D1Rs on AIIs reduces the intrinsic excitability of these cells, likely mediated by an intracellular signal transduction pathway involving cAMP, PKA, and phosphorylation of Na<subscript>v</subscript> channels in the AII-AIS. These results suggest a novel mechanism for the role of dopamine in retinal adaptation.
(Copyright © 2025 the authors.)*

*The authors declare no competing financial interests.*