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57th Annual Meeting of the German Society for Neuropathology and Neuroanatomy (DGNN)

German Society for Neuropathology and Neuroanatomy

12. - 15.09.2012, Erlangen

57th Annual Meeting of the German Society for Neuropathology and Neuroanatomy (DGNN)

Sequence of synaptogenesis in the human fetal cerebellar system

Meeting Abstract

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  • presenting/speaker Harvey B. Sarnat - University of Calgary-Alberta Children's Hospital, Pathology (Neuropathology), Calgary, Canada
  • Laura Flores-Sarnat - Alberta Children's Hospital, Calgary, Canada
  • Roland N. Auer - Universite de Montreal, Pathologie Neuropathologie), Montreal, Canada

Deutsche Gesellschaft für Neuropathologie und Neuroanatomie. 57th Annual Meeting of the German Society for Neuropathology and Neuroanatomy (DGNN). Erlangen, 12.-15.09.2012. Düsseldorf: German Medical Science GMS Publishing House; 2012. Doc12dgnnPP5.2

doi: 10.3205/12dgnn102, urn:nbn:de:0183-12dgnn1027

Published: September 11, 2012

© 2012 Sarnat et al.
This is an Open Access article distributed under the terms of the Creative Commons Attribution License ( You are free: to Share – to copy, distribute and transmit the work, provided the original author and source are credited.



Background: Precise temporal and spatial sequences of synaptogenesis occur in the cerebellar system as with other parts of the brain. It can be demonstrated by synaptophysin immunoreactivity, a synaptic vesicular wall protein found in axonal terminals of all synapses, regardless of site, function or transmitter.

Methods: Synaptophysin immunoreactivity was studied prospectively postmortem in 172 human fetuses and neonates, in nuclei of the Guillain-Mollaret triangle (dentato-olivo-rubro-cerebellar circuit), pontine nuclei and cerebellar cortex.

Results: Synaptophysin demonstrates not only a progressive increase in number of synaptic vesicles in each structure, but also the development of shape of inferior olivary and all deep cerebellar nuclei from amorphous globular neuronal aggregates. Intensity of synaptophysin reactivity is strong before the mature shape of these nuclei is achieved. The dorsal blade forms earlier than the ventral; reactivity is initially peripheral and later central. Dorsal and medial accessory olives show strong reactivity earlier than the principal olive; accessory cerebellar nuclei are reactive earlier than the dentate. Synaptogenesis in the pontine nuclei exhibits a patchy pattern reminiscent of the fetal corpus striatum and not becoming uniformly intense until 34wk. In the cerebellar cortex, morphogenesis and synaptophysin reactivity mature earlier in the vermis than the hemispheres, beginning around Purkinje cells and the molecular zone. Initiation of synaptophysin reactivity is at 13wk in the inferior olive, 16wk in the dentate, 14 wk in the red nucleus, 15wk in the pontine nuclei and vermis and 17wk in the hemisphere.

Conclusions: Development of both form and reactivity follows caudorostral and dorsoventral gradients in the longitudinal and vertical axes of the brainstem. This study of normal fetal neuroanatomy provides a basis for interpreting aberrations in timing and sequence of synaptogenesis in malformations involving the cerebellar system, in genetic and metabolic disorders, and associated with acquired fetal insults.