Structural plasticity of axon terminals in the adult

https://doi.org/10.1016/j.conb.2007.09.002Get rights and content

There is now conclusive evidence for widespread ongoing structural plasticity of presynaptic boutons and axon side-branches in the adult brain. The plasticity complements that of postsynaptic spines, but axonal plasticity samples larger volumes of neuropil, and has a larger impact on circuit remodeling. Axons from distinct neurons exhibit unique ratios of stable (t1/2 > 9 months) and dynamic (t1/2 5–20 days) boutons, which persist as spatially intermingled subgroups along terminal arbors. In addition, phases of side-branch dynamics mediate larger scale remodeling guided by synaptogenesis. The plasticity is most pronounced during critical periods; its patterns and outcome are controlled by Hebbian mechanisms and intrinsic neuronal factors. Novel experience, skill learning, life-style, and age can persistently modify local circuit structure through axonal structural plasticity.

Introduction

Structural plasticity of axons beyond developmental circuit assembly processes, and in the absence of physical lesions, is a recent discovery, and an exciting addition to the plasticity repertoire of mammalian brains. The late discovery reflects the advent of novel tools to deal with the overwhelming complexity of axonal arborisation patterns in the brain and the need to repeatedly image identified axons in situ over time periods ranging from days to months [1, 2, 3, 4]. Such repeated live imaging analysis of identified axons has proven indispensable in order to adequately document the occurrence of structural plasticity processes in axons under physiological conditions.

Although the surface has just been scratched so far, it is already clear that these novel aspects of brain plasticity can potentially match the functional impact of long-term plasticity mechanisms at pre-existing synapses. Thus, as we discuss below, structural plasticity of axons provides neuronal circuits with plasticity mechanisms that complement functional modifications of pre-existing circuitry, and might be qualitatively different from them. This is mainly due to the different time scales of the phenomena (seconds to hours, versus days to weeks), to the larger spatial scale of the modifications (axons can sample synaptic territories ranging in the tens and even hundreds of microns), and to the fact that structural plasticity can persistently modify the local architecture of microcircuits in both quantitative and qualitative ways [5••].

This review will focus on the recent evidence for structural plasticity of axon terminals in the juvenile and adult CNS in the absence of lesions or disease processes. We will begin by defining distinct types of axon terminal plasticity, then describe specific plasticity examples in the developing and adult CNS, discuss their possible significance, and close by highlighting emerging mechanistic issues that need to be addressed in our opinion. In order to focus on the plasticity of pre-existing axons under physiological conditions, this review will not address some of the more dramatic settings involving axonal plasticity in the adult. Those include axon regeneration and local sprouting to promote repair upon lesions and in disease, and adult neurogenesis [6, 7, 8, 9••]. These major plasticity processes have been treated separately in excellent reviews recently.

Section snippets

Principles of axonal plasticity in the target region

One obvious direct function of axonal structural plasticity is to locally sample potential synaptic partners and to modify local connectivity in neuronal circuits [10]. Owing to the high degree of topographic and local anatomical organization in many brain regions, the spatial extent of the axonal remodeling is likely to mirror, at least to some extent, the functional impact of the plasticity. Accordingly, it seems appropriate to subdivide axonal remodeling processes based on the spatial extent

Axonal dynamics during early postnatal life

The period of transition between the late phase of developmental circuit assembly and the onset of experience-related learning involves dramatic remodeling processes of pre-existing axons within their terminal arborisation regions. In addition to the fundamental interest of these phenomena to understand principles of brain assembly and function, the elucidation of the mechanisms involved will probably also provide insights relevant to plasticity phenomena in the adult. In the chronological

Axonal remodeling in the adult

Direct studies of the structural plasticity of axons in the adult have become possible because of the advent of genetic methods to selectively label very few neurons at any given time in vivo, achieving what can be viewed as ‘live Golgi stains’ [1, 2, 3] and to microscopy techniques allowing imaging of fluorescent samples several hundred microns deep into neural tissue [4]. In this chapter, we highlight recent live imaging studies of axonal plasticity and mention some of the more compelling

Mechanistic issues

Structural plasticity of axons raises mechanistic issues that are partly uniquely related to the specific features of individual axonal projections. Although many of these issues have not been addressed experimentally yet, their mention here should illustrate the potential for axonal plasticity to enrich the plasticity repertoire of the nervous system (Figure 2).

One major issue concerns the distinction between stable and dynamic presynaptic boutons. When axons are imaged repeatedly over many

Conclusions

The discovery that axons and presynaptic terminals exhibit vigorous structural plasticity in the juvenile and adult brain opens up new avenues to elucidate the mechanisms that mediate experience-related learning, memory, and adaptation. There seems to be a general tendency for the extent of the structural plasticity to decrease with increasing age, but the co-existence of stable and dynamic axonal circuitry is a feature shared by juvenile and adult neuronal circuits. An important feature of

References and recommended reading

Papers of particular interest, published within the period of review, have been highlighted as:

  • • of special interest

  • •• of outstanding interest

Acknowledgement

The work is supported by the Friedrich Miescher Institut, which is a branch of the Novartis Research Foundation.

References (52)

  • T. Pizzorusso et al.

    Reactivation of ocular dominance plasticity in the adult visual cortex

    Science

    (2002)
  • E. Putignano et al.

    Developmental downregulation of histone posttranslational modifications regulates visual cortical plasticity

    Neuron

    (2007)
  • B.A. Linkenhoker et al.

    Incremental training increases the plasticity of the auditory space map in adult barn owls

    Nature

    (2002)
  • J.F. Bergan et al.

    Hunting increases adaptive auditory map plasticity in adult barn owls

    J Neurosci

    (2005)
  • M. Brecht et al.

    Novel approaches to monitor and manipulate single neurons in vivo

    J Neurosci

    (2004)
  • S.L. Florence et al.

    Large-scale sprouting of cortical connections after peripheral injury in adult macaque monkeys

    Science

    (1998)
  • N. Dancause et al.

    Extensive cortical rewiring after brain injury

    J Neurosci

    (2005)
  • F.M. Bareyre et al.

    The injured spinal cord spontaneously forms a new intraspinal circuit in adult rats

    Nat Neurosci

    (2004)
  • N. Toni et al.

    Synapse formation on neurons born in the adult hippocampus

    Nat Neurosci

    (2007)
  • D.B. Chklovskii et al.

    Cortical rewiring and information storage

    Nature

    (2004)
  • E.S. Ruthazer et al.

    Control of axon branch dynamics by correlated activity in vivo

    Science

    (2003)
  • M.P. Meyer et al.

    Evidence from in vivo imaging that synaptogenesis guides the growth and branching of axonal arbors by two distinct mechanisms

    J Neurosci

    (2006)
  • C. Portera-Cailliau et al.

    Diverse modes of axon elaboration in the developing neocortex

    PLoS Biol

    (2005)
  • E.S. Ruthazer et al.

    Stabilization of axon branch dynamics by synaptic maturation

    J Neurosci

    (2006)
  • A. Das et al.

    Long-range horizontal connections and their role in cortical reorganization revealed by optical recording of cat primary visual cortex

    Nature

    (1995)
  • J.A. Kleim et al.

    Motor learning-dependent synaptogenesis is localized to functionally reorganized motor cortex

    Neurobiol Learn Mem

    (2002)
  • Cited by (0)

    1

    Equal contributions.

    View full text