Integration of the Microcircuitry of the Deep Cerebellar Nuclei into Canonical Cerebellar Circuits

[摘要] Defining the anatomical organization of cerebellar circuits has been the pursuit of neuroanatomists for over a century.The regular, repeated cytoarchitecture across the entire extent of the cerebellar cortex has led to an alluring promise that by understanding how a small patch of cortex processes information, we can generalize this finding to understand how the cortex functions as a whole.While great progress has been made to characterize cortical circuits, there has been a relative paucity of studies examining the microcircuitry of the deep cerebellar nuclei.Recent studies have shown that the deep nuclei are not passive relays of cortical processing but rather are highly sophisticated nodes within the cerebellum that have the capacity to both store memory traces and function without cortical input.The local network of the deep nuclei consists of at least six cell types and to date little information is known as to how these cells are synaptically linked, and how the cortex feeds into this network.The heterogeneity of the deep nuclei and the limitations of monosynaptic tracing techniques have hindered efforts to fully define the microcircuitry that supports nuclear processing.The advent of viral transneuronal tracing gives us the opportunity to probe the multisynaptic networks that are so characteristic of cerebellar circuits.The studies in this dissertation were designed to define the microcircuitry of the deep nuclei by utilizing monosynaptic and viral transneuronal tracing.First we provide evidence for largely non-collateralized projections from Purkinje cells onto principal or nucleo-olivary projection neurons using a dual viral tracing paradigm.In the second study we combine classical and viral tracing to provide strong evidence supporting the longstanding hypothesis that the inferior olive and cerebellum form a series of parallel, closed-loop circuits.Lastly we demonstrate, using monosynaptic tracing, a novel excitatory nucleo-cortical projection from the parvocellular interpositus nucleus targeting the Purkinje cell layer of the paraflocculus.Our studies, while confirming some aspects of cerebellar dogma, cast serious doubt onto the long held assumptions that the deep cerebellar nuclei are relay nuclei.These new findings suggest a substantial revision to cerebellar functional theories is necessary.

[发布机构] the University of Pittsburgh