IL1RAPL1 controls inhibitory networks during cerebellar development in mice

Eur J Neurosci. 2009 Oct;30(8):1476-86. doi: 10.1111/j.1460-9568.2009.06975.x. Epub 2009 Oct 7.


Abnormalities in the formation and function of cerebellar circuitry potentially contribute to cognitive deficits in humans. In the adult, the activity of the sole output neurons of the cerebellar cortex - the Purkinje cells (PCs) - is shaped by the balance of activity between local excitatory and inhibitory circuits. However, how this balance is established during development remains poorly understood. Here, we investigate the role of interleukin-1 receptor accessory protein-like 1 (IL1RAPL1), a protein linked to cognitive function which interacts with neuronal calcium sensor 1 (NCS-1) in the development of mouse cerebellum. Using Il1rapl1-deficient mice, we found that absence of IL1RAPL1 causes a transient disinhibition of deep cerebellar nuclei neurons between postnatal days 10 and 14 (P10/P14). Upstream, in the cerebellar cortex, we found developmental perturbations in the activity level of molecular layer interneurons (MLIs), resulting in the premature appearance of giant GABAA-mediated inhibitory post-synaptic currents capable of silencing PCs. Examination of feed-forward recruitment of MLIs by parallel fibres shows that during this P10/P14 time window, MLIs were more responsive to incoming excitatory drive. Thus, we conclude that IL1RAPL1 exerts a key function during cerebellar development in establishing local excitation/inhibition balance.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Anesthetics, Local / pharmacology
  • Animals
  • Animals, Newborn
  • Biophysics
  • Calbindins
  • Cerebellum / cytology*
  • Cerebellum / growth & development*
  • Electric Stimulation / methods
  • Excitatory Amino Acid Antagonists / pharmacology
  • Gene Expression Regulation, Developmental / genetics
  • In Vitro Techniques
  • Inhibitory Postsynaptic Potentials / drug effects
  • Inhibitory Postsynaptic Potentials / genetics
  • Inhibitory Postsynaptic Potentials / physiology*
  • Interleukin-1 Receptor-Like 1 Protein
  • Mice
  • Mice, Knockout
  • Neural Inhibition / drug effects
  • Neural Inhibition / genetics
  • Neural Inhibition / physiology*
  • Neuronal Calcium-Sensor Proteins / metabolism
  • Neurons / drug effects
  • Neurons / physiology*
  • Neuropeptides / metabolism
  • Parvalbumins / metabolism
  • Patch-Clamp Techniques / methods
  • Quinoxalines / pharmacology
  • Receptors, Interleukin / deficiency
  • Receptors, Interleukin / physiology*
  • S100 Calcium Binding Protein G / metabolism
  • Tetrodotoxin / pharmacology


  • Anesthetics, Local
  • Calbindins
  • Excitatory Amino Acid Antagonists
  • Il1rl1 protein, mouse
  • Interleukin-1 Receptor-Like 1 Protein
  • Neuronal Calcium-Sensor Proteins
  • Neuropeptides
  • Parvalbumins
  • Quinoxalines
  • Receptors, Interleukin
  • S100 Calcium Binding Protein G
  • frequenin calcium sensor proteins
  • 2,3-dioxo-6-nitro-7-sulfamoylbenzo(f)quinoxaline
  • Tetrodotoxin