3D electron microscopic reconstruction of segments of rat cerebellar purkinje cell dendrites receiving ascending and parallel fiber granule cell synaptic inputs

Abstract

Growing physiological evidence suggests that there are functional differences between synapses made by the ascending and parallel fiber segments of the granule axon on cerebellar Purkinje cells. Supporting this view, our previous electron microscopic studies suggested that these synapses also contacted different regions of the Purkinje cell dendrite, and in particular that ascending segment synapses are made exclusively on the smallest diameter Purkinje cell dendrites. In the current study we used serial electron microscopic techniques to reconstruct Purkinje cell dendritic segments up to almost 10 mum in length. Using a combination of anatomical and immunological labeling techniques we identified the ascending or parallel fiber origins of the excitatory synaptic inputs onto dendritic spines, as well as the location of inhibitory synapses made directly on the dendritic shaft. The results confirmed that there are regions of the Purkinje cell dendrite receiving exclusively ascending or parallel fiber synapses and that ascending segment synapses are only found on small-diameter dendrites. In addition, we describe for the first time small-diameter dendritic regions contacted by both types of excitatory synapses. While our data suggest that the majority of inhibitory inputs to the Purkinje cell tree are associated with parallel fiber synaptic inputs, we also found inhibitory inputs on dendritic regions with mixed ascending and parallel fiber inputs, or exclusively parallel fiber inputs. The finding that ascending and parallel fiber inputs can be segregated on the Purkinje cell dendritic tree provides further evidence that these excitatory granule cell synaptic inputs may be functionally distinct.

The Functional Equivalence of Ascending and Parallel Fiber Inputs in Cerebellar Computation

“…Parallel fiber and ascending inputs have received much attention because of the consequences that their relative weights may have for information processing by the circuitry of the cerebellar cortex (Llinas, 1982; Barbour, 1993; Isope and Barbour, 2002; Santamaria et al, 2002; Santamaria and Bower, 2005; Sims and Hartell, 2005, 2006; Marcaggi and Attwell, 2007; Lu et al, 2009). If the weight of an ascending input is severalfold larger than that of a parallel fiber input, then the ascending input could play a differential role in relaying information to Purkinje cells.…”

Computational Structure of the Cerebellar Molecular Layer

“…Anatomically, and as shown in Fig. 60.6, electromicrographic analyses of the zones of termination of granule cell synapses on Purkinje cell dendrites have shown that synapses of the ascending segment of the axon are restricted to only the smallest diameter dendrites, whereas parallel fiber synapses are concentrated on the larger diameter spiny dendrites (GundappaSulur et al 1999;Lu et al 2009). Accordingly, to effect the soma, the influence of ascending segment synapses must traverse regions of the Purkinje cell dendrite under direct voltage control of parallel fiber excitation and molecular layer inhibition.…”

“…With further experimental evidence suggesting that ascending synapses made numerous direct Purkinje cell contacts (Gundappa-Sulur et al 1999;Lu et al 2009;Mugnaini 1972) and had large physiological effects (Jaeger and Bower 1994;Lu et al 2005), the next question addressed using the realistic models was the lack of parallel fiber effects after granule cell layer activation. Exploring this question required that the single Purkinje cell model be embedded into a cortical network model (Santamaria et al 2007).…”

Crossing Zones in the Vestibulocerebellum: A Commentary

“…Anatomical differences in the distributions of granule cell axons and their synapses [73][74][75] are likely to be functionally quite important in determining selectivity and effectiveness across Purkinje cells. Knowledge of how individual mossy fiber terminals distribute not only with respect to cerebellar zones, but also with respect to depth within the granular layer is certainly relevant.…”