An Extracerebellar Role for Cerebellin1 in the Striatum
Kusnoor SV, Parris J, Muly EC, Morgan JI, Deutch AY. Extracerebellar role for Cerebellin1: modulation of dendritic spine density and synapses in striatal medium spiny neurons. J Comp Neurol 2010;518(13):2525-2537. doi: 10.1002/cne.22350.
Background: Cerebellin1 (Cbln1) is a secreted glycoprotein originally identified in the cerebellum, where it regulates granule cell–Purkinje cell synapses. Although widely distributed in the brain, its extracerebellar functions remain unclear. The parafascicular (PF) nucleus of the thalamus, a major source of glutamatergic input to striatal medium spiny neurons (MSNs), expresses high levels of Cbln1, suggesting that it may modulate thalamostriatal connectivity.
Hypothesis: This study hypothesized that Cbln1 expressed in PF neurons influences the synaptic organization and dendritic structure of striatal MSNs.
Methods: The authors used immunohistochemistry, tract tracing, electron microscopy and Golgi impregnation in wildtype and cbln1 knockout mice to determine Cbln1 localization and its effects on MSN morphology. Golgi-stained MSNs were reconstructed using Neurolucida to measure dendritic length and spine density.
Results: Virtually all PF neurons expressed Cbln1-immunoreactivity, whereas central medial nuclei rarely did. Cbln1-positive PF axons formed axodendritic synapses with MSNs. In cbln1-null mice, MSN dendritic spine density increased by approximately 22% compared with wildtype, while total dendritic length, spine shape and spine length distributions were unchanged. Ultrastructural analysis confirmed an increased density of axospinous asymmetric synapses without alteration in postsynaptic density length or perforation frequency.
Conclusions: The findings demonstrate an extracerebellar role for Cbln1 in shaping striatal synaptic architecture. Loss of Cbln1 increases MSN spine and synapse density, indicating that Cbln1 normally constrains excitatory connectivity within the striatum.
