Anti-hebbian long-term synaptic plasticity at the mossy fiber- Golgi cell synapse of cerebellum

This study is focused on synaptic properties of Golgi cells (GoCs), the main inhibitory neurons of cerebellar granular layer, and the presence of long-term synaptic plasticity at the mossy fibers- Golgi cell (MFs-GoC) synapses was evaluated. GoCs are characterized by an irregular soma with a diameter of 20–40 μm from which radiate several basal dendrites, two to three apical dendrites and an extensively ramified axon [1]. The most relevant excitatory input to GoCs comes from the MFs arriving to the glomeruli, thus forming synapses on basal dendrites and allowing them to mediate feedforward inhibition (MFs→GoC→GrC). Moreover, the GoCs receives connection from GrCs principally through the PFs or, in alternative, through synapses en passant along their ascending axon, enabling a feedback inhibition (MFs→GrC→GoC→GrC). GoCs also receive inhibitory signals from molecular layer neurons [5-6]. Finally, recent studies revealed the existence of inhibitory GoC-GoC communication through gap-junctions [10]. Cerebellar inhibition results from feedback and feedforward loops shaping the temporal aspect and spatial organization of signals relayed to the molecular layer. Over the years, the cerebellum has been object of many investigations on different forms of synaptic plasticity and their mechanisms of induction, which grant a critical contribution to motor learning and have the function to regulate the overall level of activity in the cerebellar circuitry. In particular, studies revealed the existence of multiple forms of long-term plasticity in the molecular layer, granular layer and DCN, thus demonstrating that the plastic capability of the cerebellum is more complex and extended than initially expected.[2]. Therefore, considering the functional implications of GoCs for granular layer network, and the importance of plasticity at other synapses, it becomes crucial to evaluate the existence of forms of plasticity at the MF-GoC synapses.