Reliable Coding Emerges from Coactivation of Climbing Fibers in Microbands of Cerebellar Purkinje Neurons

Department of Molecular Biology and Princeton Neuroscience Institute, Princeton University, Princeton, New Jersey 08544, USA.
The Journal of Neuroscience : The Official Journal of the Society for Neuroscience (Impact Factor: 6.34). 09/2009; 29(34):10463-73. DOI: 10.1523/JNEUROSCI.0967-09.2009
Source: PubMed


The inferior olive projects climbing fiber axons to cerebellar Purkinje neurons, where they trigger calcium-based dendritic spikes. These responses dynamically shape the immediate spike output of Purkinje cells as well as provide an instructive signal to guide long-term plasticity. Climbing fibers typically fire approximately once a second, and the instructive role is distributed over many such firing events. However, transmission of salient information on an immediate basis needs to occur on a shorter timescale during which a Purkinje cell would typically be activated by a climbing fiber only once. Here we show using in vivo calcium imaging in anesthetized mice and rats that sensory events are rapidly and reliably represented by momentary, simultaneous coactivation of microbands of adjacent Purkinje cells. Microbands were sagittally oriented and spanned up to 100 microm mediolaterally, representing hundreds of Purkinje cells distributed over multiple folia. Spontaneous and sensory-evoked microbands followed boundaries that were close or identical to one another and were desynchronized by olivary injection of the gap junction blocker mefloquine, indicating that excitation to the olive is converted to synchronized firing by electrical coupling. One-time activation of microbands could distinguish a sensory response from spontaneous activity with up to 98% accuracy. Given the anatomy of the olivocerebellar system, microband synchrony may shape the output of neurons in the cerebellar nuclei either via powerful inhibition by Purkinje cells or by direct monosynaptic excitation from the inferior olive.

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    • ". ( A ) Configuration of AM - ester injection and imaging . ( B ) Resulting staining of tissue 60 min after injection of indicator . Purkinje cells can be seen as vertical stripes with occasional brighter spots ( corresponding to dendrites ; scale bar = 20 μm ) . ( C ) Active Purkinje cell dendrites identified using a spatial PCA / ICA algorithm ( Ozden et al . , 2009 ) . ( D ) Fluorescence traces from the identified dendrites , using the same color code as in ( C ) . The timing of the sensory stimulus ( foot shock ) is indicated by the underlying grey bars . ( E ) Stimulus triggered averages of 20 stimulus presentations . Note that all cells except for the third ( orange ) show a stimulus - locked r"
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    • "This assumption seems to agree with experimental observations. For example, an air-puff stimulus (a potentially nociceptive stimulus which warrants closing the eyelid) can be reliably decoded when ensemble information is used, but not using the response of individual cells [72]. In another example , phase of locomotion has a rather small modulatory effect on climbing fiber activity, but perturbations cause much larger responses [100]. "
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    • "Furthermore, early investigators demonstrated that because CF bursts are ''all or nothing'' (Crill, 1970), they evoke the same electrical response in the soma of the postsynaptic PC (i.e., a complex spike [CS]) regardless of whether the CF input fired spontaneously or in response to a sensory event (Eccles et al., 1966). These classic electrophysiology studies led to the current view of cerebellar learning, according to which all individual CF bursts are equivalent, and therefore to obtain information about sensory-driven instructive signals, one must collect responses to CF inputs over many learning trials or many PCs (Gibson et al., 2004; Houk et al., 1996; Mauk and Donegan, 1997; Ozden et al., 2009; Schultz et al., 2009). Our experiments challenge the classical view that spontaneous and sensory-driven CF inputs are equivalent. "
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