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• W2950377514 endingPage "12166" @default.
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• W2950377514 abstract "Combinatorial expansion by the cerebellar granule cell layer (GCL) is fundamental to theories of cerebellar contributions to motor control and learning. Granule cells (GrCs) sample approximately four mossy fiber inputs and are thought to form a combinatorial code useful for pattern separation and learning. We constructed a spatially realistic model of the cerebellar GCL and examined how GCL architecture contributes to GrC combinatorial diversity. We found that GrC combinatorial diversity saturates quickly as mossy fiber input diversity increases, and that this saturation is in part a consequence of short dendrites, which limit access to diverse inputs and favor dense sampling of local inputs. This local sampling also produced GrCs that were combinatorially redundant, even when input diversity was extremely high. In addition, we found that mossy fiber clustering, which is a common anatomical pattern, also led to increased redundancy of GrC input combinations. We related this redundancy to hypothesized roles of temporal expansion of GrC information encoding in service of learned timing, and we show that GCL architecture produces GrC populations that support both temporal and combinatorial expansion. Finally, we used novel anatomical measurements from mice of either sex to inform modeling of sparse and filopodia-bearing mossy fibers, finding that these circuit features uniquely contribute to enhancing GrC diversification and redundancy. Our results complement information theoretic studies of granule layer structure and provide insight into the contributions of granule layer anatomical features to afferent mixing. SIGNIFICANCE STATEMENT Cerebellar granule cells are among the simplest neurons, with tiny somata and, on average, just four dendrites. These characteristics, along with their dense organization, inspired influential theoretical work on the granule cell layer as a combinatorial expander, where each granule cell represents a unique combination of inputs. Despite the centrality of these theories to cerebellar physiology, the degree of expansion supported by anatomically realistic patterns of inputs is unknown. Using modeling and anatomy, we show that realistic input patterns constrain combinatorial diversity by producing redundant combinations, which nevertheless could support temporal diversification of like combinations, suitable for learned timing. Our study suggests a neural substrate for producing high levels of both combinatorial and temporal diversity in the granule cell layer." @default.
• W2950377514 created "2019-06-27" @default.
• W2950377514 creator A5037108237 @default.
• W2950377514 creator A5091012126 @default.
• W2950377514 date "2017-11-08" @default.
• W2950377514 modified "2023-09-25" @default.
• W2950377514 title "Morphological Constraints on Cerebellar Granule Cell Combinatorial Diversity" @default.
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• W2950377514 doi "https://doi.org/10.1523/jneurosci.0588-17.2017" @default.
• W2950377514 hasPubMedCentralId "https://www.ncbi.nlm.nih.gov/pmc/articles/5729189" @default.
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• W2950377514 hasPublicationYear "2017" @default.
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