GABA modulates development of cerebellar Purkinje cell dendrites under control of endocannabinoid signaling.
Purkinje cells (PCs) are the sole projection neurons in the cerebellar cortex with highly arborized dendrites, on which they receive glutamatergic and GABAergic inputs. Whereas influences of glutamatergic inputs on dendritic development of PCs have been well studied, those of GABA remain elusive. Here we examined effects of GABAergic signaling on dendritogenesis of PCs in dissociated cerebellar cultures. Treatment with GABA(A) agonists such as muscimol altered Purkinje dendrites to longer and less branched morphology, while GABA(A) antagonists resulted in shorter dendrites. In contrast, neither a GABA(B) agonist nor antagonist had major effects on dendritic morphology. Simultaneous addition of a glutamatergic antagonist cocktail or the Trk receptor antagonist K252a did not block muscimol. Furthermore, blockade of endocannabinoid signaling by either AM251 or tetrahydrolipstatin resulted in longer and less branched dendrites similar to those treated with GABA(A) agonists suggesting upstream regulation by endocannabinoids. Notably, whereas Purkinje dendrites extended in random directions in the presence of muscimol, they oriented to coexisting GABAergic interneurons when treated with AM251. Taken together, our results postulate the hypothesis that GABA released from the cerebellar interneurons modulates dendritogenesis of PCs in an endocannabinoid-dependent manner in the developing cerebellar cortex.
Kawaguchi
Koji
K
Division of Developmental Neurobiology, Department of Physiology and Cell Biology, Kobe University Graduate School of Medicine, Chuo-ku, Kobe, Japan.
Habara
Tomomi
T
Terashima
Toshio
T
Kikkawa
Satoshi
S
D000818:Animals; D019208:Brain-Derived Neurotrophic Factor / Q000502:physiology; D063385:Cannabinoid Receptor Modulators / Q000502:physiology*; D002465:Cell Movement; D002478:Cells, Cultured; D003712:Dendrites / Q000187:drug effects / Q000502:physiology*; D063388:Endocannabinoids; D058785:GABA-A Receptor Agonists; D018698:Glutamic Acid / Q000502:physiology; D007395:Interneurons / Q000502:physiology; D051379:Mice; D008810:Mice, Inbred C57BL; D008813:Mice, Inbred ICR; D009118:Muscimol / Q000494:pharmacology; D011689:Purkinje Cells / Q000502:physiology / Q000648:ultrastructure*; D011963:Receptors, GABA-A / Q000502:physiology; D015398:Signal Transduction; D013997:Time Factors; D005680:gamma-Aminobutyric Acid / Q000502:physiology*
D019208:Brain-Derived Neurotrophic Factor; D063385:Cannabinoid Receptor Modulators; D063388:Endocannabinoids; D058785:GABA-A Receptor Agonists; D011963:Receptors, GABA-A; D009118:Muscimol; D018698:Glutamic Acid; D005680:gamma-Aminobutyric Acid