Cerebellar Golgi cells (GoCs) efficiently control the spiking activity of granule
cells through GABAA receptor-mediated tonic and phasic inhibition. Recent experiments
provided compelling evidence for the extensive interconnection of GoCs through electrical
synapses, but their chemical inhibitory synaptic inputs are debated. Here, we investigated
the GABAergic synaptic inputs of GoCs using in vitro electrophysiology and quantitative
light microscopy (LM) and electron microscopy (EM). We characterized GABAA receptor-mediated
IPSCs in GoCs and Lugaro cells (LuCs), and found that IPSCs in GoCs have lower frequencies,
smaller amplitudes, and much slower decay kinetics. Pharmacological and LM immunolocalization
experiments revealed that GoCs express alpha3, whereas LuCs express alpha1 subunit-containing
GABAA receptors. The selective expression and clustered distribution of the alpha3
subunit in GoCs allowed the quantitative analysis of GABAergic synapses on their dendrites
in the molecular layer (ML). EM and LM experiments in rats, and wild-type and GlyT2-GFP
transgenic mice revealed that only one third of axon terminals establishing GABAergic
synapses on GoC dendrites contain GlyT2, ruling out LuCs, globular cells, and any
noncortical glycinergic inputs as major inhibitory sources. We also show that axon
terminals of stellate/basket cells very rarely innervate GlyT2-GFP-expressing GoCs,
indicating that only a minority of the inhibitory inputs to GoCs in the ML originates
from local interneurons, and the majority of their inhibitory inputs exclusively releases
GABA.
