Glutamatergic Neurotransmission from Melanopsin Retinal Ganglion Cells is Required for Neonatal Photoaversion but Not Adult Pupillary Light Reflex

Overview

Journal PLoS One

Specialties General Medicine
Science

Date 2014 Jan 7

PMID 24391855

Citations 14

Authors

Anton Delwig

Sriparna Majumdar

Kelly Ahern

Matthew M LaVail

Robert Edwards

Thomas S Hnasko

David R Copenhagen

Affiliations

Soon will be listed here.

Abstract

Melanopsin-expressing retinal ganglion cells (mRGCs) in the eye play an important role in many light-activated non-image-forming functions including neonatal photoaversion and the adult pupillary light reflex (PLR). MRGCs rely on glutamate and possibly PACAP (pituitary adenylate cyclase-activating polypeptide) to relay visual signals to the brain. However, the role of these neurotransmitters for individual non-image-forming responses remains poorly understood. To clarify the role of glutamatergic signaling from mRGCs in neonatal aversion to light and in adult PLR, we conditionally deleted vesicular glutamate transporter (VGLUT2) selectively from mRGCs in mice. We found that deletion of VGLUT2 in mRGCs abolished negative phototaxis and light-induced distress vocalizations in neonatal mice, underscoring a necessary role for glutamatergic signaling. In adult mice, loss of VGLUT2 in mRGCs resulted in a slow and an incomplete PLR. We conclude that glutamatergic neurotransmission from mRGCs is required for neonatal photoaversion but is complemented by another non-glutamatergic signaling mechanism for the pupillary light reflex in adult mice. We speculate that this complementary signaling might be due to PACAP neurotransmission from mRGCs.

Citing Articles

Developmental control of rod number via a light-dependent retrograde pathway from intrinsically photosensitive retinal ganglion cells.

DSouza S, Upton B, Eldred K, Glass I, Nayak G, Grover K Dev Cell. 2024; 59(21):2897-2911.e6.

PMID: 39142280 PMC: 11537824. DOI: 10.1016/j.devcel.2024.07.018.

Role of glutamate in the development of visual pathways.

Majumdar S Front Ophthalmol (Lausanne). 2024; 3:1147769.

PMID: 38983097 PMC: 11182277. DOI: 10.3389/fopht.2023.1147769.

Regulation of mouse exploratory behaviour by irradiance and cone-opponent signals.

Tamayo E, Mouland J, Lucas R, Brown T BMC Biol. 2023; 21(1):178.

PMID: 37605163 PMC: 10441731. DOI: 10.1186/s12915-023-01663-6.

The Retinal Basis of Light Aversion in Neonatal Mice.

Caval-Holme F, Aranda M, Chen A, Tiriac A, Zhang Y, Smith B J Neurosci. 2022; 42(20):4101-4115.

PMID: 35396331 PMC: 9121827. DOI: 10.1523/JNEUROSCI.0151-22.2022.

Age and Sex-Dependent ADNP Regulation of Muscle Gene Expression Is Correlated with Motor Behavior: Possible Feedback Mechanism with PACAP.

Kapitansky O, Sragovich S, Jaljuli I, Hadar A, Giladi E, Gozes I Int J Mol Sci. 2020; 21(18).

PMID: 32937737 PMC: 7555576. DOI: 10.3390/ijms21186715.

References

Fyk-Kolodziej B, Dzhagaryan A, Qin P, Pourcho R . Immunocytochemical localization of three vesicular glutamate transporters in the cat retina. J Comp Neurol. 2004; 475(4):518-30. DOI: 10.1002/cne.20199. View

Johnson J, Fremeau Jr R, Duncan J, Renteria R, Yang H, Hua Z . Vesicular glutamate transporter 1 is required for photoreceptor synaptic signaling but not for intrinsic visual functions. J Neurosci. 2007; 27(27):7245-55. PMC: 2443709. DOI: 10.1523/JNEUROSCI.0815-07.2007. View

Engelund A, Fahrenkrug J, Harrison A, Hannibal J . Vesicular glutamate transporter 2 (VGLUT2) is co-stored with PACAP in projections from the rat melanopsin-containing retinal ganglion cells. Cell Tissue Res. 2010; 340(2):243-55. DOI: 10.1007/s00441-010-0950-3. View

Hannibal J, Fahrenkrug J . Target areas innervated by PACAP-immunoreactive retinal ganglion cells. Cell Tissue Res. 2004; 316(1):99-113. DOI: 10.1007/s00441-004-0858-x. View

Delwig A, Logan A, Copenhagen D, Ahn A . Light evokes melanopsin-dependent vocalization and neural activation associated with aversive experience in neonatal mice. PLoS One. 2012; 7(9):e43787. PMC: 3441538. DOI: 10.1371/journal.pone.0043787. View

Scherrer G, Low S, Wang X, Zhang J, Yamanaka H, Urban R . VGLUT2 expression in primary afferent neurons is essential for normal acute pain and injury-induced heat hypersensitivity. Proc Natl Acad Sci U S A. 2010; 107(51):22296-301. PMC: 3009833. DOI: 10.1073/pnas.1013413108. View

Engelund A, Fahrenkrug J, Harrison A, Luuk H, Hannibal J . Altered pupillary light reflex in PACAP receptor 1-deficient mice. Brain Res. 2012; 1453:17-25. DOI: 10.1016/j.brainres.2012.03.005. View

Hnasko T, Chuhma N, Zhang H, Goh G, Sulzer D, Palmiter R . Vesicular glutamate transport promotes dopamine storage and glutamate corelease in vivo. Neuron. 2010; 65(5):643-56. PMC: 2846457. DOI: 10.1016/j.neuron.2010.02.012. View

Fahrenkrug J, Nielsen H, Hannibal J . Expression of melanopsin during development of the rat retina. Neuroreport. 2004; 15(5):781-4. DOI: 10.1097/00001756-200404090-00008. View

10.

Fremeau Jr R, Voglmaier S, Seal R, Edwards R . VGLUTs define subsets of excitatory neurons and suggest novel roles for glutamate. Trends Neurosci. 2004; 27(2):98-103. DOI: 10.1016/j.tins.2003.11.005. View

11.

Johnson J, Sherry D, Liu X, Fremeau Jr R, Seal R, Edwards R . Vesicular glutamate transporter 3 expression identifies glutamatergic amacrine cells in the rodent retina. J Comp Neurol. 2004; 477(4):386-98. PMC: 2586940. DOI: 10.1002/cne.20250. View

12.

McNeill D, Sheely C, Ecker J, Badea T, Morhardt D, Guido W . Development of melanopsin-based irradiance detecting circuitry. Neural Dev. 2011; 6:8. PMC: 3070623. DOI: 10.1186/1749-8104-6-8. View

13.

Schmidt-Supprian M, Rajewsky K . Vagaries of conditional gene targeting. Nat Immunol. 2007; 8(7):665-8. DOI: 10.1038/ni0707-665. View

14.

Tian N, Copenhagen D . Visual stimulation is required for refinement of ON and OFF pathways in postnatal retina. Neuron. 2003; 39(1):85-96. DOI: 10.1016/s0896-6273(03)00389-1. View

15.

Hatori M, Le H, Vollmers C, Keding S, Tanaka N, Buch T . Inducible ablation of melanopsin-expressing retinal ganglion cells reveals their central role in non-image forming visual responses. PLoS One. 2008; 3(6):e2451. PMC: 2396502. DOI: 10.1371/journal.pone.0002451. View

16.

Ecker J, Dumitrescu O, Wong K, Alam N, Chen S, LeGates T . Melanopsin-expressing retinal ganglion-cell photoreceptors: cellular diversity and role in pattern vision. Neuron. 2010; 67(1):49-60. PMC: 2904318. DOI: 10.1016/j.neuron.2010.05.023. View

17.

Johnson J, Wu V, Donovan M, Majumdar S, Renteria R, Porco T . Melanopsin-dependent light avoidance in neonatal mice. Proc Natl Acad Sci U S A. 2010; 107(40):17374-8. PMC: 2951438. DOI: 10.1073/pnas.1008533107. View

18.

Hannibal J . Neurotransmitters of the retino-hypothalamic tract. Cell Tissue Res. 2002; 309(1):73-88. DOI: 10.1007/s00441-002-0574-3. View

19.

Kawaguchi C, Isojima Y, Shintani N, Hatanaka M, Guo X, Okumura N . PACAP-deficient mice exhibit light parameter-dependent abnormalities on nonvisual photoreception and early activity onset. PLoS One. 2010; 5(2):e9286. PMC: 2823792. DOI: 10.1371/journal.pone.0009286. View

20.

Stella Jr S, Li S, Sabatini A, Vila A, Brecha N . Comparison of the ontogeny of the vesicular glutamate transporter 3 (VGLUT3) with VGLUT1 and VGLUT2 in the rat retina. Brain Res. 2008; 1215:20-9. PMC: 2562175. DOI: 10.1016/j.brainres.2008.03.038. View