Experiencia Y Plasticidad

REVIEWS

Experience-dependent structural synaptic plasticity in the mammalian brain
Anthony Holtmaat* and Karel Svoboda‡

Abstract | Synaptic plasticity in adult neural circuits may involve the strengthening or weakening of existing synapses as well as structural plasticity, including synapse formation and elimination. Indeed, long-term in vivo imaging studies are beginning to reveal thestructural dynamics of neocortical neurons in the normal and injured adult brain. Although the overall cell-specific morphology of axons and dendrites, as well as of a subpopulation of small synaptic structures, are remarkably stable, there is increasing evidence that experiencedependent plasticity of specific circuits in the somatosensory and visual cortex involves cell type-specific structuralplasticity: some boutons and dendritic spines appear and disappear, accompanied by synapse formation and elimination, respectively. This Review focuses on recent evidence for such structural forms of synaptic plasticity in the mammalian cortex and outlines open questions.
Neural circuits are defined by the structure of axons and dendrites and the synapses that connect them. Axons route a neuron’soutput to diverse target regions, which can span most of the brain. Individual dendrites integrate inputs from several sources over hundreds of micrometers. In the adult brain, circuit changes mediated by structural plasticity, accompanied by synapse formation and elimination, are thought to underlie aspects of long-term memory formation1. Given that in most areas of the brain, including the cerebralcortex, neurons are sparsely connected, structural plasticity could provide a substantial boost in the memory storage capacity, compared with plasticity due to changes in synaptic strength alone2. Structural rearrangements over long distances allows more variability and therefore a larger number of potential circuits to be generated, implying a larger memory capacity per synapse. Structuralplasticity might also be involved in recovery from brain injury 3–5. Neuronal processes are studded with a high density of synapses. A synapse is typically defined by the presence of a presynaptic active zone with synaptic vesicles, a well-defined synaptic cleft and a postsynaptic density (PSD)6,7. Most excitatory cortical synapses occur at contacts between axonal en passant boutons and dendriticspines. En passant boutons are small axonal varicosities that typically contain one active zone and one cluster of synaptic vesicles8. A subpopulation of axons, for example those of cortical layer 6 pyramidal cells, harbours a high density of terminaux boutons that often form synapses with dendritic shafts9. Spines are tiny protrusions that emanate from the dendritic shaft 10. Typically one bouton andone spine correspond to one synapse6,8. A small number of boutons8 and spines11–14 lack synapses and a few boutons participate in more than one synapse (multiple synapse boutons, MSBs)8,14–17. Electron microscopy (EM) reconstructions have revealed that spines are structurally extremely diverse: their volumes can range from 0.001 to 1 μm3,18,19; their shapes include thin, filopodia-like protrusions(‘thin spines’), short spines without a well-defined spine neck (‘stubby spines’) and spines with a large bulbous head (‘mushroom spines’)18,20. Different cortical cells, and perhaps even individual cells within a class, can have dramatically different spine densities21–23. Changes in synaptic connectivity through the de novo growth and retraction of dendritic spines and axonal boutons mightcontribute to functional changes in the brain. Compared with synaptic strength changes alone, such structural spine plasticity would hugely increase the memory storage capacity of the brain, because a large number of synaptic connectivity patterns are attainable by spine or bouton growth, even without large-scale remodelling of dendritic and axonal
voluME 10 | SEPTEMBEr 2009 | 647 © 2009 Macmillan...