Recent advances in understanding the mechanisms of cerebellar granule cell development and function and their contribution to behavior

Roy V. Sillitoe, Elizabeth P. Lackey, Detlef Heck

Research output: Contribution to journalReview article

Abstract

The cerebellum is the focus of an emergent series of debates because its circuitry is now thought to encode an unexpected level of functional diversity. The flexibility that is built into the cerebellar circuit allows it to participate not only in motor behaviors involving coordination, learning, and balance but also in non-motor behaviors such as cognition, emotion, and spatial navigation. In accordance with the cerebellum's diverse functional roles, when these circuits are altered because of disease or injury, the behavioral outcomes range from neurological conditions such as ataxia, dystonia, and tremor to neuropsychiatric conditions, including autism spectrum disorders, schizophrenia, and attention-deficit/hyperactivity disorder. Two major questions arise: what types of cells mediate these normal and abnormal processes, and how might they accomplish these seemingly disparate functions? The tiny but numerous cerebellar granule cells may hold answers to these questions. Here, we discuss recent advances in understanding how the granule cell lineage arises in the embryo and how a stem cell niche that replenishes granule cells influences wiring when the postnatal cerebellum is injured. We discuss how precisely coordinated developmental programs, gene expression patterns, and epigenetic mechanisms determine the formation of synapses that integrate multi-modal inputs onto single granule cells. These data lead us to consider how granule cell synaptic heterogeneity promotes sensorimotor and non-sensorimotor signals in behaving animals. We discuss evidence that granule cells use ultrafast neurotransmission that can operate at kilohertz frequencies. Together, these data inspire an emerging view for how granule cells contribute to the shaping of complex animal behaviors.

Original languageEnglish (US)
Article number1142
JournalF1000Research
Volume7
DOIs
StatePublished - Jan 1 2018

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Animals
Networks (circuits)
Electric wiring
Stem cells
Gene expression
Navigation
Cerebellum
Stem Cell Niche
Developmental Genes
Animal Behavior
Dystonia
Tremor
Cell Lineage
Ataxia
Attention Deficit Disorder with Hyperactivity
Epigenomics
Synaptic Transmission
Synapses
Cognition
Schizophrenia

All Science Journal Classification (ASJC) codes

  • Biochemistry, Genetics and Molecular Biology(all)
  • Immunology and Microbiology(all)
  • Pharmacology, Toxicology and Pharmaceutics(all)

Cite this

Recent advances in understanding the mechanisms of cerebellar granule cell development and function and their contribution to behavior. / Sillitoe, Roy V.; Lackey, Elizabeth P.; Heck, Detlef.

In: F1000Research, Vol. 7, 1142, 01.01.2018.

Research output: Contribution to journalReview article

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