Experience-Dependent Synaptic Plasticity in the Developing Cerebral Cortex

Chiye Aoki, Alev Erisir

Research output: Chapter in Book/Report/Conference proceedingChapter


This chapter will review some of the mechanisms of synaptic plasticity in the developing cerebral cortex, as revealed by neuroanatomical studies. We describe the electron microscopic data that capture synaptogenesis and synapse pruning in detail. The neurotransmitter systems that we will cover are glutamate, gamma-aminobutyric acid (GABA), norepinephrine, and acetylcholine. The topics included in this chapter are not only the important ones but also can best be described as those to which the authors have had the most direct research experience.Scrutiny of the timing of synaptogenesis and pruning across the species indicates that these two processes are not as simply aligned to the beginning and the end of the critical period (CP) for ocular dominance plasticity. On the contrary, synaptogenesis is robust, with synapse number increasing by as much as 30-fold during the early postnatal period and continuing even as synaptic plasticity begins to wane. This indicates that the waning of plasticity toward the end of the CP is quite an active process, rather than a reflection of some production line that winds down with time. Search for a brake in the CP has yielded multiple excellent candidates. One is Lynx1 that antagonizes the nicotinic acetylcholine receptors, which, in turn, brings the cholinergic system to the forefront among the players enabling synaptic plasticity during the CP. Another is the extracellular perineuronal net that stabilizes synapses formed upon the fast-spiking GABAergic interneurons and reduces the excitability of these interneurons. This latter point, together with the fact that the GABAergic neurons themselves undergo ocular dominance shifts and express high levels of cholinergic receptors, indicates that activity-dependent synapse rearrangement at the surface of GABAergic neurons could be a particularly important process underlying plasticity of the cortical circuit during the CP. This point compels us to better understand the molecular mechanisms of GABAergic synaptogenesis. An important player implicated in this process is the brain-derived neurotrophic factor.Given that norepinephrine is a permissive factor enabling plasticity of receptive field properties, the shift in the noradrenergic receptor expression from synapses to glia could be a factor contributing to the ending of the CP. Calcium is regarded as an important ion to enable synaptic plasticity. Therefore, synaptic transmission that allows for more Ca2+ influx (e.g. via the NR2B-containing N-methyl-d-aspartate receptors (NMDARs)) might be thought to be better than the alternative that allows for less (NR2A-containing NMDARs). However, the rise of NR2A-subunits aligns better with the onset of the CP, and it is the decline of the NR2B-subunits in layer 4 (the thalamocortical (TC) input layer) but not in layers 2/3, that aligns better with the end of the ocular dominance CP. These, among many other observations, point to the importance of considering layer-, and therefore circuit, specific changes during the CP. A structural change that is temporally correlated with developmental plasticity is the postsynaptic protrusions in layer 4 that invaginate the TC axon terminals. These highly specialized structures peak at the CP.Ultrastructural analysis of GABA receptor (GABAR) expression indicates that changes can be specific not only to the cortical layer but also to the cell type within the layer. For example, sensorineural activity-dependent regulation of the plasmalemmal expression of GABAR is evident for the pyramidal cells but not for the inhibitory interneurons, and it is the nonsynaptic GABARs mediating tonic inhibition of pyramidal neurons that increase at the plasma membrane at the onset of puberty. The combined electron microscopic and immunocytochemical approaches have been valuable for identifying activity-dependent changes in the developing cortical circuitry that are layer-specific, cell type-specific, and plasma membrane-specific and for discriminating changes that occur at the synapse, perisynaptically and nonsynaptically.

Original languageEnglish (US)
Title of host publicationThe Synapse
Subtitle of host publicationStructure and Function
PublisherElsevier Inc.
Number of pages49
ISBN (Print)9780124186750
StatePublished - Dec 2013


  • Acetylcholine
  • Cerebral Cortex
  • Critical Period
  • Electron Microscopy
  • GABA
  • Glutamate
  • Hippocampus
  • Muscarinic Receptors
  • NMDA
  • Nicotinic Receptors
  • Norepinephrine
  • Ocular Dominance Column Plasticity
  • Synapse
  • Synapse Morphology
  • Synaptic Plasticity
  • Synaptogenesis

ASJC Scopus subject areas

  • General Neuroscience


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