Session: Session 2
Adaptive Response of the Visual Thalamus to Imbalanced Sensory Input: Proteomic Insights into Molecular Mechanisms in Amblyopia
Introduction
Amblyopia arises from neuronal adaptation due to abnormal experience of one eye during a critical period of visual development early in childhood. The molecular mechanisms underlying amblyopia are not yet fully characterized. To investigate this process, we used the monocular deprivation experimental paradigm in young rats to induce plasticity of neuronal excitability in dorsal lateral geniculate nucleus (dLGN) neurons (Duménieu et al., BioRxiv 2023).
Method
We isolated dLGN regions tied to the deprived and spared eyes from rats subjected to monocular deprivation for 4-, 7-, and 10-days using microdissection. The protein content of the samples was analyzed by liquid chromatography coupled with high-resolution mass spectrometry (LC-MS/MS). Isobaric labeling (Tandem Mass Tag – 18plex TMTpro reagents) was used to enhance mass spectrometry sensitivity and enable relative quantification by mixing the samples. Data analysis was performed using MaxQuant 2.5, Perseus 2.0.11, and Proteome Discoverer 3.0.
Results
Our preliminary data analysis identified modulation of protein expression in rats monocularly deprived for 4-, 7-, and 10-days. Specifically, we observed significant changes in the levels of proteins essential for intrinsic and synaptic neuronal excitability. Key proteins, such as ion channels or proteins involved in synaptic transmission, showed altered expression patterns, indicating their potential role in the adaptive processes of the dLGN in response to monocular deprivation. These protein alterations suggest mechanisms by which neuronal circuits in the dLGN adapt to altered visual input.
Conclusion
Employing a proteomic approach, we identified activity-dependent dynamic changes in the components of dLGN neurons. These discoveries enhance our understanding of the molecular mechanisms linked to activity-driven regulation of neuronal excitability in amblyopia.
Amblyopia arises from neuronal adaptation due to abnormal experience of one eye during a critical period of visual development early in childhood. The molecular mechanisms underlying amblyopia are not yet fully characterized. To investigate this process, we used the monocular deprivation experimental paradigm in young rats to induce plasticity of neuronal excitability in dorsal lateral geniculate nucleus (dLGN) neurons (Duménieu et al., BioRxiv 2023).
Method
We isolated dLGN regions tied to the deprived and spared eyes from rats subjected to monocular deprivation for 4-, 7-, and 10-days using microdissection. The protein content of the samples was analyzed by liquid chromatography coupled with high-resolution mass spectrometry (LC-MS/MS). Isobaric labeling (Tandem Mass Tag – 18plex TMTpro reagents) was used to enhance mass spectrometry sensitivity and enable relative quantification by mixing the samples. Data analysis was performed using MaxQuant 2.5, Perseus 2.0.11, and Proteome Discoverer 3.0.
Results
Our preliminary data analysis identified modulation of protein expression in rats monocularly deprived for 4-, 7-, and 10-days. Specifically, we observed significant changes in the levels of proteins essential for intrinsic and synaptic neuronal excitability. Key proteins, such as ion channels or proteins involved in synaptic transmission, showed altered expression patterns, indicating their potential role in the adaptive processes of the dLGN in response to monocular deprivation. These protein alterations suggest mechanisms by which neuronal circuits in the dLGN adapt to altered visual input.
Conclusion
Employing a proteomic approach, we identified activity-dependent dynamic changes in the components of dLGN neurons. These discoveries enhance our understanding of the molecular mechanisms linked to activity-driven regulation of neuronal excitability in amblyopia.