Commun Biol. 2025 May 12. 8(1): 731
Cerebellar Golgi cells (GoCs), segregate parallel fiber (pf), and mossy fiber (mf) inputs on apical and basal dendrites. Computational modeling predicted that this anatomical arrangement, coupled with a specific ionic channel localization, could be instrumental to drive STDP at mf-GoC synapses. Here, we test this hypothesis with GoC patch-clamp recordings in acute mouse cerebellar slices. Repeated mf-pf pairing on the theta-band within a ± 50 ms time window induces anti-symmetric Hebbian-STDP, with spike-timing long-term potentiation or depression (st-LTP or st-LTD) occurring when action potentials (APs) elicited by pf stimulation follow or precede the activation of mf synapses, respectively. Mf-GoC STDP induction requires AP backpropagation from apical to basal dendrites, NMDA receptor activation at mf-GoC synapses, and intracellular calcium changes. Importantly, STDP is inverted by inhibitory control. Thus, experimental evidence confirms and extends model predictions suggesting that GoC STDP can bind molecular layer to granular layer activity, regulating cerebellar computation and learning.