The cerebellar network: revisiting the critical issues

Abstract

The cerebellum forms one of the main neuronal circuits of the brain. It is involved in motor control and its dysfunction causes the well known neurological syndrome called ataxia. However, despite decades of research, its mechanisms of function still remain elusive. This faith is peculiar indeed, if one considers the remarkable prediction made in the 1980s that cerebellum was soon going to be understood in principle (Sir J.C. Eccles in Ito, 1984). The fact is that, once scientists moved from anatomy-based models (e.g. the renowned motor learning theory of D. Marr; Marr, 1969) to cellular physiology, the cerebellar circuit became quite hard to understand. Cerebellar neurons have dynamic properties, which are not yet fully resolved and complicate (not to say often conflict with) theoretical predictions (reviewed in D'Angelo et al. 2010). Psychophysics has demonstrated that the cerebellum regulates timing of movement and that it can make use of implicit memory to perform the operation called ‘sensory prediction’ (Ivry et al. 2002; Ivry & Spencer, 2004; Spencer & Ivry, 2009). Neurophysiology has confirmed extremely fast precise sequences of neuronal activation as well as several sites of long-term synaptic plasticity, providing cues to interpret the phenomenological observations. However, a precise relationship between cellular properties and the mechanisms of cerebellum in coordinating movement cannot be established yet. An exemplar issue is that of parallel fibre–Purkinje cell LTD, which has been predicted by theory and then observed in vitro, but its role in vivo is hard to demonstrate (Le Guen & De Zeeuw, 2010; Schonewille et al. 2011). At the same time, other forms of plasticity have been reported, whose role also remains to be determined (Hansel et al. 2001). Other critical and related problems concern elaboration of time codes in the granular layer (D'Angelo & De Zeeuw, 2009; D'Angelo et al. 2009) and other circuit sections (De Zeeuw et al. 2011), contrasting the still diffused idea that frequency codes represent the main way for transmitting neuronal information. Still debated is also signal processing in the subcircuit composed by inferior olivary neurons, deep cerebellar nuclear neurons and Purkinje cells (Jacobson et al. 2008; Llinas, 2009), as well as the role of parallel fibres in signal transmission from granular to molecular layer (Rokni et al. 2007) and the function of the main neurons of the cerebellar cortex and nuclei. Understanding these issues is clearly fundamental and preliminary to the interpretation of cerebellar circuit function. These issues were debated at the meeting The cerebellum: from neurons to higher control and cognition, held in Pavia, Italy, 8–9 July 2010. As a fundamental aspect of the cerebellum, Rodolfo Llinas (Llinas, 2011) reviews here the dispute between cerebellar motor learning and cerebellar motor timing. The fundamental role of climbing fibres in controlling spike emission is re-evaluated with respect to their impact on long-term plasticity at the parallel fibre–Purkinje cell synapse. As far as timing emerges as a fundamental property of the circuit, important correlates are found in cerebellar neurons and synapses. Along with a review of the intrinsic excitable mechanism of Purkinje cells, here the specific role of SK channels is considered in detail (Hosy et al. 2011). The anomaly in Ca2+-dependent K+-channels has been recently related to forms of cerebellar ataxia (see also Libster et al. 2010; Rinaldo & Hansel, 2010; Hosy et al. 2011). A further step ahead in the circuit, the still unclear functional properties of deep cerebellar nuclei are considered by Uusisaari & De Schutter (2011). Finally, a general theoretical framework potentially capable of incorporating the salient properties of cerebellar cellular processing, the adaptive filter theory, is presented in comparison with classical theories of the cerebellum (Dean & Porrill, 2011; see also Dean & Porrill, 2010; Dean et al. 2010). The meeting programme and abstracts can be found at: http://www.frontiersin.org/events/The Cerebellum from neurons t 1/1095/cellular neuroscience