Traveling waves in developing cerebellar cortex mediated by asymmetrical Purkinje cell connectivity

Abstract

Correlated network activity plays a critical role in the development of many neural circuits. Purkinje cells are among the first neurons to populate the cerebellar cortex, where they sprout exuberant axon collaterals. Here we use multiple patch-clamp recordings targeted with two-photon microscopy to characterize monosynaptic connections between Purkinje cells of juvenile mice. We show that Purkinje cell axon collaterals project asymmetrically in the sagittal plane, directed away from the lobule apex. Based on our anatomical and physiological characterization of this connection, we construct a network model that robustly generates waves of activity traveling along chains of connected Purkinje cells. Consistent with the model, we observe traveling waves of activity in Purkinje cells in sagittal slices from young mice that require GABAA receptor-mediated transmission and intact Purkinje cell axon collaterals. These traveling waves are absent in adult animals, suggesting they play a developmental role in wiring the cerebellar cortical microcircuit.

Voltage-Sensitive Dye Imaging Reveals Dynamic Spatiotemporal Properties of Cortical Activity after Spontaneous Muscle Twitches in the Newborn Rat

“…A traveling component to movement-related activity would be consistent with activity in many developing neural systems (Calderon et al, 2005;Firth et al, 2005;Watt et al, 2009). In sensory areas, they promote homotopic connections by synchronizing cortical regions receiving afferent inputs from adjacent sensory organs (Feller, 1999).…”

“…Distinct patterns of neural activity are found in different neural systems (Yvert et al, 2004;Crépel et al, 2007;Tritsch et al, 2007;Watt et al, 2009), and, in some cases, the function of these patterns has been determined (Torborg and Feller, 2005;Huberman, 2007;Wu et al, 2010). Distinct patterns of neural activity are present within the developing mammalian cortex as well (Garaschuk et al, 2000;Adelsberger et al, 2005;Dupont et al, 2006;Yang et al, 2009;Colonnese and Khazipov, 2010;Seelke and Blumberg, 2010;Minlebaev et al, 2011).…”

Developmental Switching of Perisomatic Innervation from Climbing Fibers to Basket Cell Fibers in Cerebellar Purkinje Cells

“…The rest of the inhibitory fibers were collectively classified as other fibers, which included recurrent PC axons characterized by relatively dark axoplasm filled with dense synaptic vesicles (Fig. 2 F) (Watt et al, 2009) and unidentified afferent fibers. Free spines lacking any synaptic contact were often encountered during development; they were encapsulated by either BFs (Fig.…”

Response of traveling waves to transient inputs in neural fields

“…A similar weight kernel was considered in a study of directionally selective networks of visual cortex [40], and there are several experimental studies supporting the existence of functionally specific asymmetries in the spatial organization of synaptic inputs [41][42][43]. The nonlinearity f (u) represents the relationship between synaptic input and output firing rate.…”

“…which allows us to compute the null space V (ξ) of the adjoint operator (42). The homogeneous version of the left hand side has solutions of the form Be −ξ/c .…”