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Extracerebellar role for Cerebellin1: modulation of dendritic spine density and synapses in striatal medium spiny neurons.

Cerebellin1 (Cbln1) is a secreted glycoprotein that was originally isolated from the cerebellum and subsequently found to regulate synaptic development and stability. Cbln1 has a heterogeneous distribution in brain, but the only site in which it has been shown to have central effects is the cerebellar cortex, where loss of Cbln1 causes a reduction in granule cell-Purkinje cell synapses. Neurons of the thalamic parafascicular nucleus (PF), which provide glutamatergic projections to the striatum, also express high levels of Cbln1. We first examined Cbln1 in thalamostriatal neurons and then determined if cbln1 knockout mice exhibit structural deficits in striatal neurons. Virtually all PF neurons express Cbln1-immunoreactivity (-ir). In contrast, only rare Cbln1-ir neurons are present in the central medial complex, the other thalamic region that projects heavily to the dorsal striatum. In the striatum Cbln1-ir processes are apposed to medium spiny neuron (MSN) dendrites; ultrastructural studies revealed that Cbln1-ir axon terminals form axodendritic synapses with MSNs. Tract-tracing studies found that all PF cells retrogradely labeled from the striatum express Cbln1-ir. We then examined the dendritic structure of Golgi-impregnated MSNs in adult cbln1 knockout mice. MSN dendritic spine density was markedly increased in cbln1(-/-) mice relative to wildtype littermates, but total dendritic length was unchanged. Ultrastructural examination revealed an increase in the density of MSN axospinous synapses in cbln1(-/-) mice, with no change in postsynaptic density length. Thus, Cbln1 determines the dendritic structure of striatal MSNs, with effects distinct from those seen in the cerebellum.

Pubmed ID: 20503425 RIS Download

Mesh terms: Aging | Animals | Axons | Corpus Striatum | Dendritic Spines | Male | Mice | Mice, Knockout | Nerve Tissue Proteins | Neural Pathways | Neurons | Protein Precursors | Rats | Rats, Sprague-Dawley | Synapses | Thalamus

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Associated grants

  • Agency: NINDS NIH HHS, Id: NS042828
  • Agency: NINDS NIH HHS, Id: P01 NS044282
  • Agency: NIMH NIH HHS, Id: R01 MH077298
  • Agency: NCRR NIH HHS, Id: R01 RR00165
  • Agency: NINDS NIH HHS, Id: NS051537
  • Agency: NCRR NIH HHS, Id: P51 RR000165
  • Agency: NCI NIH HHS, Id: CA21765
  • Agency: NINDS NIH HHS, Id: R01 NS051537
  • Agency: NCI NIH HHS, Id: P30 CA021765
  • Agency: NINDS NIH HHS, Id: F31 NS061528-02
  • Agency: NINDS NIH HHS, Id: R01 NS042828
  • Agency: NINDS NIH HHS, Id: P01 NS44282
  • Agency: NINDS NIH HHS, Id: F31 NS061528
  • Agency: NIMH NIH HHS, Id: R01MH-077298

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