Intrinsic excitement in cerebellar nuclei neurons during learning

Understanding the mechanisms underlying learning and memory continues to be of major interest in the neuroscientific discourse. Worldwide, over 50 million people live with some form of memory disorder, and this number will increase with the aging of our society. Synaptic plasticity is considered the main cellular correlate of learning in the brain, yet extrasynaptic changes in membrane excitability may also contribute. The possible roles of changes in membrane excitability during learning and memory have only started to be explored in the last few decades. In the hippocampus, possible functions of membrane excitability in memory allocation and the promotion of cell assembly formation during memory consolidation have been highlighted (1). In the cerebellum, and more specifically the cerebellar cortex, synaptic plasticity may establish connectivity patterns via action potential firing, whereas intrinsic plasticity may facilitate a neuron to get integrated into an active engram (2, 3). The cerebellum offers an ideal system to study basic mechanisms underlying learning and memory because of its evolutionarily well-preserved neuroarchitecture and the well-characterized forms of motor learning that it controls. In PNAS, Wang et al. (4) demonstrate learning-induced changes in membrane excitability in cerebellar nuclei projection neurons, which together with the vestibular nuclei neurons, form the main output of the cerebellum. Early in the 20th century, delay eyeblink conditioning (EBC) was recognized as an elegant and simple form of associative learning (5), but it was not until the end of the century that changes in membrane excitability during EBC learning were studied as one of the potential mechanisms (6, 7). Pioneering work by Schreurs et al. (6) showed that cerebellar Purkinje cells, which inhibit the nuclei neurons (Fig. 1 A ), display learning-related changes in membrane excitability 24 h and 1 mo after EBC learning, pointing toward both a short-term and long-term role of intrinsic … [↵][1]1To whom correspondence should be addressed. Email: c.canto{at}nin.knaw.nl. [1]: #xref-corresp-1-1