TY - JOUR T1 - Only a minority of the inhibitory inputs to cerebellar Golgi cells originates from local GABAergic cells JF - eneuro JO - eneuro DO - 10.1523/ENEURO.0055-16.2016 SP - ENEURO.0055-16.2016 AU - Mark D. Eyre AU - Zoltan Nusser Y1 - 2016/05/12 UR - http://www.eneuro.org/content/early/2016/05/09/ENEURO.0055-16.2016.abstract N2 - 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- (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 α3, whereas LuCs express α1 subunit-containing GABAA receptors. The selective expression and clustered distribution of the α3 subunit in GoCs allowed the quantitative analysis of GABAergic synapses on their dendrites in the molecular layer (ML). EM and LM experiments in rats, 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 non-cortical 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.Significance Statement: Golgi cells are essential for controlling the activity of granule cells in the cerebellum by releasing the inhibitory neurotransmitter GABA, but very little is known about the sources of their own inhibition. We used functional and morphological techniques to demonstrate that the inhibitory postsynaptic receptors on Golgi cells are unique among the cell types in the cerebellar cortex, and used these unique GABAA receptors to visualize GoC inhibitory synapses and their presynaptic inputs. This study extends our understanding of cerebellar microcircuits by demonstrating that only a minority of the inhibitory inputs to Golgi cells originate from GABAergic cells of the cerebellar cortex. ER -