General and variable features of varicosity spacing along unmyelinated axons in the hippocampus and cerebellum

Shepherd, G. M. G., Raastad, M., Andersen, P. (April 2002) General and variable features of varicosity spacing along unmyelinated axons in the hippocampus and cerebellum. Proceedings of the National Academy of Sciences of the United States of America, 99 (9). pp. 6340-6345. ISSN 0027-8424

URL: http://www.ncbi.nlm.nih.gov/pubmed/11972022
DOI: 10.1073/pnas.052151299

Abstract

Along unmyelinated central axons, synapses occur at focal swellings called axonal varicosities (boutons). The mechanisms regulating how frequently synapses and varicosities occur along axons remain poorly understood. Here, to investigate varicosity distribution patterns and the extent to which they may be conserved across different axons, we analyzed varicosity numbers and positions along fluorescently labeled axon branches in hippocampal area CA1 (CA3-to-CA1 “Schaffer collateral” axons) and five other synaptic regions of rat hippocampus and cerebellum. Varicosity spacing varied by region; e.g., 3.7 ± 0.6 μm (mean ± SD) for CA3-to-CA1 axons and 5.2 ± 1.0 μm for cerebellar parallel fibers. Surprisingly, when 56 axons from these different regions were pooled into a single heterogeneous group, a general relationship emerged: the spacing variability (SD) was a constant fraction of the mean spacing, suggesting that varicosities along different axons are distributed in a fundamentally similar, scaled manner. Varicosity spacing was neither regular nor random but followed a pattern consistent with random synaptic distributions and the occurrence of multiple-synapse boutons. A quantitative model reproduced the salient features of the data and distinguished between two proposed mechanisms relating axonal morphogenesis and synaptogenesis. Arborizing varicose axons in the central nervous system are complex circuit elements: a single hippocampal CA3 cell axon makes ≈50,000 synapses over ≈0.2 m, all within the hippocampus (1, 2). Understanding connectivity in specific circuits requires detailed quantitative information about axonal synaptic distributions. At the ultrastructural level, synaptic boutons have been characterized as ≈1-μm long (3–5) varicosities that usually occur en passant along the axon, separated from other varicosities by short axonal shaft segments. For CA3-to-CA1 and other axons, the average synapse/varicosity ratio is 1.1–1.7 (4–11), reflecting the occurrence of multiple-synapse boutons (MSBs). MSBs may serve as intermediate or final stages of morphological plasticity associated with long-term synaptic plasticity (12–17). The organization of varicosities and their synapses over longer axonal distances merits quantification for several reasons. First, varicosity spacing is a key aspect of the complex geometry of axon–dendrite interactions. Second, synaptic and varicosity distribution patterns likely reflect fundamental connectivity rules. The report by Hellwig et al. (18) of a purely random pattern along neocortical axons carries numerous implications but has not yet been extended to other axon types. Third, varicosity spacing patterns may hold clues about mechanisms of synaptogenesis and development, an unexplored possibility relevant for synaptic plasticity models invoking varicosity neogenesis (15, 16, 19). Here, we used the strategy of quantifying varicosity spacing and its variability at the single axonal branch level for diverse types of central varicose axons, focusing on hippocampal CA3-to-CA1 axons and cerebellar parallel fibers but also including hippocampal axons in more heterogeneous populations to enable comparisons across a variety of axons.

Item Type: Paper
Subjects: organs, tissues, organelles, cell types and functions > tissues types and functions > axon
organs, tissues, organelles, cell types and functions > tissues types and functions > cerebellum
organs, tissues, organelles, cell types and functions > tissues types and functions > hippocampus
organs, tissues, organelles, cell types and functions > tissues types and functions
CSHL Authors:
Communities: CSHL labs > Svoboda lab
Depositing User: Matt Covey
Date: April 2002
Date Deposited: 31 Oct 2013 16:33
Last Modified: 31 Oct 2013 16:33
PMCID: PMC122950
Related URLs:
URI: http://repository.cshl.edu/id/eprint/28787

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