Associative learning elicits the formation of multiple-synapse boutons

Yuri Geinisman*, Robert W. Berry, John F. Disterhoft, John M. Power, Eddy A. Van Der Zee

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

214 Scopus citations


The formation of new synapses has been suggested to underlie learning and memory. However, previous work from this laboratory has demonstrated that hippocampus-dependent associative learning does not induce a net gain in the total number of hippocampal synapses and, hence, a net synaptogenesis. The aim of the present work was to determine whether associative learning involves a specific synaptogenesis confined to the formation of multiple-synapse boutons (MSBs) that synapse with more than one dendritic spine. We used the behavioral paradigm of trace eyeblink conditioning, which is a hippocampus-dependent form of associative learning. Conditioned rabbits were given daily 80-trial sessions to a criterion of 80% conditioned responses in a session. During each trial, the conditioned stimulus (tone) and the unconditioned stimulus (corneal airpuff) were presented with an intervening trace interval of 500 msec. Brain tissue was taken for morphological analyses 24 hr after the last session. Unbiased stereological methods were used for obtaining estimates of the total number of MSBs in the stratum radiatum of hippocampal subfield CA1. The results showed that the total number of MSBs was significantly increased in conditioned rabbits as compared with pseudoconditioned or unstimulated controls. This conditioning-induced change, which occurs without a net synaptogenesis, reflects a specific synaptogenesis resulting in MSB formation. Models of the latter process are proposed. The models postulate that it requires spine motility and may involve the relocation of existing spines from nonactivated boutons or the outgrowth of newly formed spines for specific synaptogenesis with single-synapse boutons activated by the conditioning stimulation.

Original languageEnglish (US)
Pages (from-to)5568-5573
Number of pages6
JournalJournal of Neuroscience
Issue number15
StatePublished - Aug 1 2001


  • Associative learning
  • CA1 stratum radiatum
  • Multiple-synapse boutons
  • Nippocampus
  • Spine motility
  • Synaptic plasticity
  • Synaptogenesis
  • Trace eyeblink conditioning

ASJC Scopus subject areas

  • Neuroscience(all)


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