Regulation of the Serotonergic System by Kainate in the Avian Retina
Serotonin (5-HT) has been recognized as a neurotransmitter in the vertebrate retina, restricted mainly to amacrine and bipolar cells. It is involved with synaptic processing and possibly as a mitogenic factor. We confirm that chick retina amacrine and bipolar cells are, respectively, heavily and faintly immunolabeled for 5-HT. Amacrine serotonergic cells also co-express tyrosine hydroxylase (TH), a marker of dopaminergic cells in the retina. Previous reports demonstrated that serotonin transport can be modulated by neurotransmitter receptor activation. As 5-HT is diffusely released as a neuromodulator and co-localized with other transmitters, we evaluated if 5-HT uptake or release is modulated by several mediators in the avian retina. The role of different glutamate receptors on serotonin transport and release in vitro and in vivo was also studied. We show that l-glutamate induces an inhibitory effect on [3H]5-HT uptake and this effect was specific to kainate receptor activation. Kainate-induced decrease in [3H]5-HT uptake was blocked by CNQX, an AMPA/kainate receptor antagonist, but not by MK-801, a NMDA receptor antagonist. [3H]5-HT uptake was not observed in the presence of AMPA, thus suggesting that the decrease in serotonin uptake is mediated by kainate. 5-HT (10–50 μM) had no intrinsic activity in raising intracellular Ca2+, but addition of 10 μM 5-HT decreased Ca2+ shifts induced by KCl in retinal neurons. Moreover, kainate decreased the number of bipolar and amacrine cells labeled to serotonin in chick retina. In conclusion, our data suggest a highly selective effect of kainate receptors in the regulation of serotonin functions in the retinal cells.
KeywordsSerotonin Glutamate receptors Retina Kainate
Grants from Fundação de Amparo à Pesquisa do Estado do Rio de Janeiro (FAPERJ), Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq), Instituto Nacional de Ciência e Tecnologia de Neurociência Translacional (INCT-INNT), Instituto Nacional de Ciência e Tecnologia de Neuroimodulação (INCT-NIM), and Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES) supported this work. DPF thanks CAPES/Brazil for doctoral fellowships. JLMN and AMH thank CNPQ for the individual research fellowship. KCC and RAMR thank CNPq and FAPERJ for the individual research fellowship. We thank Granja Americano (Santa Izabel Alimento LTDA) for kindly providing Fertilized White Leghorn eggs (Gallus gallus) for our experiments.
Conceived and designed the experiments: LSS, HRF, KCC, RAMR, and JLMN. Performed the experiments: ACFP, SMAL, LSS, HRF, FAFR, and DPF. Analyzed the data: AMH, KRHMO, KCC, RAMR, and JLMN. Contributed reagents/materials/analysis tools: KCC, RAMR, and JLMN. Wrote the paper and financial support and administrative support: KCC, RAMR, and JLMN.
This study was funded by CNPq (Grant number 552491/2011-0).
Compliance with Ethical Standards
Conflict of interest
The authors declare that they have no conflict of interest.
All experiments involving animals were approved and carried out in accordance with the guidelines of the Institutional Animal Care and Use Committee of the Federal University of Pará (permit number 85/15) and Federal University of Rio de Janeiro (permit number IBCCF-035).
- Connaughton, V., 1995. Glutamate and Glutamate Receptors in the Vertebrate Retina, In: Kolb, H., Fernandez, E., Nelson, R. (Eds.), Webvision: The Organization of the Retina and Visual System,University of Utah Health Sciences Center, Salt Lake City (UT)Google Scholar
- da Silva Sampaio L, Kubrusly RCC, Colli YP, Trindade PP, Ribeiro-Resende VT, Einicker-Lamas M, Paes-de-Carvalho R, Gardino PF, de Mello FG, De Melo Reis RA (2018) Cannabinoid receptor type 1 expression in the developing avian retina: morphological and functional correlation with the dopaminergic system. Front Cell Neurosci 12:58CrossRefGoogle Scholar
- Kubrusly RCC, Gunter A, Sampaio L, Martins RS, Schitine CS, Trindade P, Fernandes A, Borelli-Torres R, Miya-Coreixas VS, Rego Costa AC, Freitas HR, Gardino PF, de Mello FG, Calaza KC, Reis RAM (2018) Neuro-glial cannabinoid receptors modulate signaling in the embryonic avian retina. Neurochem Int 112:27–37CrossRefGoogle Scholar
- Trakhtenberg EF, Pita-Thomas W, Fernandez SG, Patel KH, Venugopalan P, Shechter JM, Morkin MI, Galvao J, Liu X, Dombrowski SM, Goldberg JL (2017) Serotonin receptor 2C regulates neurite growth and is necessary for normal retinal processing of visual information. Dev Neurobiol 77:419–437CrossRefGoogle Scholar