Developmental remodeling of ampa and nmda subunit composition at the rod bipolar cell dyad synapse in the mouse retina
Fecha
2024-01
Autores
Profesor Guía
Formato del documento
Thesis
ORCID Autor
Título de la revista
ISSN de la revista
Título del volumen
Editor
Universidad de Valparaíso
Ubicación
ISBN
ISSN
item.page.issne
item.page.doiurl
Facultad
Departamento o Escuela
Facultad de Ciencias. Programa de Doctorado en Ciencias Mención en Neurociencia
Determinador
Recolector
Especie
Nota general
Doctorado en Ciencias Biológicas mención Neurociencia
Resumen
During postnatal development, synaptic connections undergo dynamic refinement involving structural and functional changes in response to neuronal activity. In the visual system, the onset of visual experience, marked by eye opening (~P14), triggers synaptic remodeling processes, including modifications in synaptic receptor composition. In the retina, the rod pathway, a conserved circuitry across mammalian species, mediates dim light vision. Here, rod bipolar cells (RBCs) provide glutamatergic inputs to GABAergic A17 and glycinergic AII amacrine cells (ACs). While AII ACs transfer signals to ON and OFF pathway, A17 ACs make reciprocal inhibitory feedback synapses onto the same RBC axon terminal, modulating the time course of visual signaling in vivo. While at the time of eye opening, these synapses undergo extensive modifications leading to the maturation of fundamental components that enable inhibitory signaling, including GABA receptors (GABARs), it remains unclear whether the maturation and stabilization of RBC dyad synapses during development involve changes in the subunit composition of ionotropic glutamate receptors (iGluRs) and whether these changes require visual experience.
In this thesis, using acute retinal slices from normally- and dark-reared mice and a combination of electrophysiological, pharmacological, and optical approaches, we investigate whether light-dependent synaptic activity (i.e. visual experience), drives a switch in the subunit composition of AMPARs and/or NMDARs at the RBC dyad synapse, allowing for the stabilization of feedforward and feedback synaptic connections of this circuit.
We found that: (1) the mEPSC frequency increases with age in both AII and A17 ACs, but the amplitude and kinetics change only in AII ACs. These changes were unaffected by visual deprivation, except for the mEPSC frequency onto AII ACs, which was enhanced. (2) In the mouse retina, the expression of CP-AMPARs in AII ACs remained unchanged throughout development, while NMDARs were not functionally expressed. No changes were induced by visual deprivation. (3) In A17 amacrine cells, AMPARs transition from calcium-impermeable (with an atypical pharmacological profile) to calcium-permeable, while NMDARs transition from GluN2B- to GluN2A-containing receptors. This change in iGluRs subunit composition was not modified by visual deprivation. (4) The GABAergic reciprocal feedback, which requires CP-AMPARs activation, onto RBC axon terminals is absent before eye opening, likely by the lack of expression of CP-AMPARs before eye opening. (5) Interestingly, the synaptic strength of the GABAergic reciprocal feedback is reduced by visual deprivation, an effect that can be reversed by exposing visually deprived animals to light.
Together, our results indicate that extensive refinement of the mechanisms facilitating feedforward excitatory and feedback inhibitory signaling at the RBC dyad synapse occurs during retinal development. Most of these changes are independent of visual experience. Additionally, our findings underscore the distinct iGluRs profiles exhibited by AII and A17 amacrine cells, suggesting that both cell types follow unique programs of synaptic refinement and development.
Descripción
Lugar de Publicación
Auspiciador
• Programa de doctorado en Ciencias Biológicas mención Neurociencia, Facultad de
Ciencias, Universidad de Valparaíso.
• Proyecto FONDECYT 1151091 y 1201848.
• Centro Interdisciplinario de Neurociencia (CINV): Proyecto código P09-022F
Palabras clave
RETINA, CELULAS BIPOLARES, SINAPSIS