Connexin43 and Bergmann glial gap junctions in cerebellar function

Mika Tanaka

doi:10.3389/neuro.01.038.2008

Abstract

Connexin43 (Cx43), a major component of astrocytic gap junctions, is abundantly expressed in Bergmann glial cells (BGCs) in the cerebellum, but the function of Cx43 in BGCs is largely unknown. BGCs are specialized astrocytes closely associated with Purkinje cells. Here, we review our recent studies of the role of Cx43 in gap junctional coupling between BGCs and in cerebellar function. We generated Cx43 conditional knockout mice with an S100b-Cre transgenic line (Cx43fl/fl:S100b-Cre), in which there was a significant postnatal loss of Cx43 in BGCs and cerebellar astrocytes. Gap junctional coupling between BGCs measured by dye coupling was virtually abolished in Cx43fl/fl:S100b-Cre mice. Electrophysiologic and behavioral analyses suggested that Cx43-mediated gap junctions and Cx43 hemichannels in BGCs are not necessary for the neuron-glia interactions required for cerebellum-dependent motor coordination and motor learning. These findings raise questions regarding the regional differences in the impact of the loss of Cx43 in the brain.

Highlights

Astrocytes, the most abundant cell type in the mammalian brain, are extensively coupled by gap junctions (Giaume and McCarthy, 1996) through which ionic and metabolic homeostasis is maintained, and electrical coupling and intercellular signaling (e.g., Ca2+ wave) occur (Ransom and Ye, 2005)
Using a new Cx43 conditional knockout (CKO) model, we recently investigated the contribution of Cx43 to gap junctional coupling between Bergmann glial cells (BGCs), and examined whether Cx43 in BGCs, either as a gap junction channel or a hemichannel, plays an important role in cerebellar functions via Purkinje cell-BGC interactions
The restricted nature of the S100bCre-mediated deletion might explain the lack of rotarod impairment in the Cx43 floxed allele (Cx43fl)/fl:S100b-Cre mice, because the functions of other brain regions can affect motor coordination (Blundell et al, 2008)

Summary

Introduction

Astrocytes, the most abundant cell type in the mammalian brain, are extensively coupled by gap junctions (Giaume and McCarthy, 1996) through which ionic and metabolic homeostasis (e.g., spatial buffering of K+ and glutamate) is maintained, and electrical coupling and intercellular signaling (e.g., Ca2+ wave) occur (Ransom and Ye, 2005). To investigate the role of Cx43 in cerebellar function, we constructed a new Cx43 CKO model with temporal and regional specificity of a Cre-mediated recombination directed to the cerebellum (Tanaka et al, 2008), as deficits in other brain areas, e.g., striatum, can lead to impaired motor coordination (Blundell et al, 2008).

Results

Conclusion