Associative Learning Elicits the Formation of Multiple-Synapse Boutons

Abstract

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.

Mechanism for long-term memory formation when synaptic strengthening is impaired

“…Hippocampus-dependent LTM formation has been associated with de novo synaptogenesis, a form of structural plasticity (7,8,27). Those studies, however, did not establish whether synaptogenesis contributes to memory as functional plasticity and modulation of neuronal excitability could be sufficient.…”

Drug-Paired Contextual Stimuli Increase Dendritic Spine Dynamics in Select Nucleus Accumbens Neurons

“…Dendrites underwent automatic software reconstruction (Imaris, Bitplane; Supplementary Data S7; Shen et al, 2008Shen et al, , 2009. Dendritic spine tip densities were higher than overall spine densities because some protrusions had multiple heads, a phenomenon associated with conditioning (Geinisman et al, 2001). …”

Neuronal and morphological bases of cognitive decline in aged rhesus monkeys

“…The frequencies of single-synapse boutons, multiplesynapse boutons (MSBs), and boutons with no apparent synaptic contacts (nonsynaptic boutons, NSBs) in the OML were determined using serial section electron microscopy. MSBs are presynaptic boutons synaptically connected to more than one dendritic spine and potentially act as a morphological substrate to increase coupling between presynaptic and postsynaptic neurons (Harris 1995;Toni et al 1999;Geinisman et al 2001;Yankova et al 2001). MSBs are implicated in structural plasticity and hippocampus-dependent associative learning Toni et al 1999;Geinisman et al 2001).…”

“…MSBs are presynaptic boutons synaptically connected to more than one dendritic spine and potentially act as a morphological substrate to increase coupling between presynaptic and postsynaptic neurons (Harris 1995;Toni et al 1999;Geinisman et al 2001;Yankova et al 2001). MSBs are implicated in structural plasticity and hippocampus-dependent associative learning Toni et al 1999;Geinisman et al 2001). While there are no age effects on bouton density or average size in the DG OML, the proportion of NSBs is doubled in aged compared to young monkeys (Hara et al 2011), suggesting that aging results in a lower turnover or higher retraction of spines, leading to a greater proportion of boutons that fail to make or maintain a synaptic contact.…”