Spatial Pattern Coding of Sensory Information by Climbing Fiber-Evoked Calcium Signals in Networks of Neighboring Cerebellar Purkinje Cells

Abstract

Climbing fiber input produces complex spike synchrony across populations of cerebellar Purkinje cells oriented in the parasagittal axis. Elucidating the fine spatial structure of this synchrony is crucial for understanding its role in the encoding and processing of sensory information within the olivocerebellar cortical circuit. We investigated these issues using in vivo multineuron two-photon calcium imaging in combination with information theoretic analysis. Spontaneous dendritic calcium transients linked to climbing fiber input were observed in multiple neighboring Purkinje cells. Spontaneous synchrony of calcium transients between individual Purkinje cells falls off over ϳ200 m mediolaterally, consistent with the presence of cerebellar microzones organized by climbing fiber input. Synchrony was increased after administration of harmaline, consistent with an olivary origin. Periodic sensory stimulation also resulted in a transient increase of synchrony after stimulus onset. To examine how synchrony affects the neural population code provided by the spatial pattern of complex spikes, we analyzed its information content. We found that spatial patterns of calcium events from small ensembles of cells provided substantially more stimulus information (59% more for seven-cell ensembles) than available by counting events across the pool without taking into account spatial origin. Information theoretic analysis indicated that, rather than contributing significantly to sensory coding via stimulus dependence, correlational effects on sensory coding are dominated by redundancy attributable to the prevalent spontaneous synchrony. The olivocerebellar circuit thus uses a labeled line code to report sensory signals, leaving open a role for synchrony in flexible selection of signals for output to deep cerebellar nuclei.

Dendritic Calcium Signaling Triggered by Spontaneous and Sensory-Evoked Climbing Fiber Input to Cerebellar Purkinje Cells In Vivo

“…This result also implies that the sensory inputs provided by inferior olive neurons through CFs rely on their precise timing and the spatiotemporal activation patterns in the local population of Purkinje cells Sasaki et al, 1989;Ozden et al, 2009;Schultz et al, 2009) in order for them to be discriminated from spontaneous CF input.…”

“…Although CF-evoked dendritic Ca 2ϩ signals have been detected in vivo using bulk loading or electroporation of [Ca 2ϩ ] indicators into Purkinje cells (Sullivan et al, 2005;Mukamel et al, 2009;Ozden et al, 2009;Schultz et al, 2009;Chen et al, 2010), quantitative characterization of the magnitude and spatial spread of the Ca 2ϩ signals and their precise relationship with electrical activity has thus far only been possible in vitro (Konnerth et al, 1992;Miyakawa et al, 1992;Wang et al, 2000). It is crucial to obtain this information in vivo, particularly given that dendritic excitability can be modulated by action potential firing, background excitatory and inhibitory synaptic input, and activity in neuromodulatory afferents.…”

Ablation of Glutamate Receptor GluRδ2 in Adult Purkinje Cells Causes Multiple Innervation of Climbing Fibers by Inducing Aberrant Invasion to Parallel Fiber Innervation Territory

“…Longitudinal olivocerebellar micro- zones have been identified in the cerebellar cortex, based on high synchrony of complex spike activity Sasaki et al, 1989;Sugihara et al, 1993;Lang et al, 1999;Fukuda et al, 2001) and Ca 2ϩ spikes (Ozden et al, 2008;Mukamel et al, 2009;Schultz et al, 2009). Each microzone is ϳ500 m in width, stable across behavioral states, and has sharp boundary with the neighboring microzones (Mukamel et al, 2009).…”

Estimating Information-Theoretic Quantities

“…However, the components can also be written as a sum of entropies and entropy--like quantities, which can then be computed using the entropy estimation algorithms described earlier in this chapter (Pola et al, 2003;Montani et al, 2007;Schultz et al, 2009). Note that, as shown by Scaglione and colleagues (Scaglione et al, 2008(Scaglione et al, , 2010) the components in Eq.…”