Open Collections

Robinson, Kaylie

University of British Columbia

The cerebellar cortex has been shown to have roles in motor control, emotion and cognition, and alterations in these functions have been implicated in psychiatric disorders. The molecular composition of different synapse types across the cerebellar cortex is essential for the proper execution of these functions. Mapping of synaptic components has begun with glutamate receptors using immunogold electron microscopy but has yet to be done with many synaptic components. Many synaptic signalling and scaffolding proteins have important roles at the synapse, and have been associated with a multitude of psychiatric disorders, including schizophrenia and autism spectrum disorder. In the following study, we used an adapted version of magnified analysis of the proteome to map the localization of a variety of excitatory synaptic components at major synapse types in the molecular and granule cell layers of the cerebellar cortex. In the molecular layer, we show differential expression of synaptic proteins with AMPA receptors being more highly expressed in molecular layer interneuron to Purkinje cell and climbing fibre to Purkinje cell synapses, Shank1 and SynGAP being more highly expressed in parallel fibre to Purkinje cell synapses, Shank2 being more highly expressed at parallel fibre to Purkinje cell synapses and climbing fibre to Purkinje cell synapses, and Shank3 being expressed at all synapse types. These results show not only cell type specific differences but input specific differences in synaptic proteins in the molecular layer. In the granule cell layer, we show differential expression of synaptic components at synaptic versus extrasynaptic sites, with AMPA receptors being more highly expressed at synaptic sites, and NMDA receptors being more highly expressed at extrasynaptic sites. A similar expression pattern as for NMDA receptors was shown for SynGAP, where Shank3 and SAPAP1 showed equal expression across synaptic and extrasynaptic sites. The results from the granule cell layer show evidence that NMDA receptors and synGAP are localized at adherens junctions in the granule cell glomeruli, suggesting roles in structural regulation. Overall, these results contribute to the development of a cerebellar synaptome.

Text

2024-04-12

Attribution-NonCommercial-NoDerivatives 4.0 International

http://hdl.handle.net/2429/87791

Neuroscience

University of British Columbia

UBCV

http://creativecommons.org/licenses/by-nc-nd/4.0/