Structural Components of Synaptic Plasticity and Memory Consolidation

Consolidation of implicit memory in the invertebrate Aplysia and explicit memory in the mammalian hippocampus are associated with remodeling and growth of preexisting synapses and the formation of new synapses. Here, we compare and contrast structural components of the synaptic plasticity that underlies these two distinct forms of memory. In both cases, the structural changes involve time-dependent processes. Thus, some modifications are transient and may contribute to early formative stages of long-term memory, whereas others are more stable, longer lasting, and likely to confer persistence to memory storage. In addition, we explore the possibility that trans-synaptic signaling mechanisms governing de novo synapse formation during development can be reused in the adult for the purposes of structural synaptic plasticity and memory storage. Finally, we discuss how these mechanisms set in motion structural rearrangements that prepare a synapse to strengthen the same memory and, perhaps, to allow it to take part in other memories as a basis for understanding how their anatomical representation results in the enhanced expression and storage of memories in the brain.Santiago Ramón y Cajal (1894) used the insights provided by his remarkable light microscopic observations of neurons selectively stained with the Golgi method to propose the first cellular theory of memory storage as an anatomical change in the functional connections between nerve cells, later called synapses (Sherrington 1897). For most of the last century, chemical synapses were thought to convey information in only one direction—from the presynaptic to the postsynaptic neuron. It now is clear that synaptic transmission is a bidirectional and self-modifiable form of cell–cell communication (Peters et al. 1976; Jessell and Kandel 1993). This appreciation of reciprocal signaling between pre- and postsynaptic elements is consistent with other forms of intercellular communication and provides a conceptual framework for understanding memory-induced changes in the structure of the synapse. Indeed, an increasing body of evidence suggests that trans-synaptic signaling and coordinated recruitment of pre- and postsynaptic mechanisms underlie consolidation of both implicit and explicit forms of memory storage (Marrone 2005; Hawkins et al. 2006; Bailey et al. 2008).Studies in a variety of systems have found that molecular mechanisms of consolidation and long-term storage of memory begin at the level of the synapse. Existing proteins are modified, signals are sent back to the nucleus so that specific genes are expressed, and gene products are transported back to the synapse where the local synthesis of new protein is triggered to allow for the remodeling, addition, and elimination of synapses (Bailey and Kandel 1985; Bailey et al. 1996; Kandel 2001; Bourne and Harris 2008, 2012). These structural components of synaptic plasticity are thought to represent a cellular change that contributes to both implicit and explicit memory consolidation (Greenough and Bailey 1988; Bailey and Kandel 1993; Bailey et al. 2005; Bourne and Harris 2008, 2012). The association between alterations in the structure and/or number of synapses and memory storage has led to numerous studies regarding the signaling pathways that might couple molecular changes to structural changes. In addition, parallel homeostatic mechanisms have been identified that can trigger synaptic scaling, which serves to stabilize the strengthened synapses while weakening or eliminating other synapses, thus providing specificity during memory consolidation (Bourne and Harris 2011; Schacher and Hu 2014).In this review, we compare and contrast structural changes at the synapse during both implicit and explicit memory consolidation, as well as the molecular signaling pathways that initiate the learning-induced structural changes versus those that serve to maintain these changes over time. Toward that end, we will focus on two experimental model systems and several prototypic forms of synaptic plasticity that we have worked on and that have been extensively studied as representative examples of memory storage: long-term habituation and sensitization of the gill-withdrawal reflex in Aplysia. These are examples of implicit memory consolidation and hippocampal-based long-term potentiation (LTP) and long-term depression (LTD), as candidate mechanisms for the synaptic plasticity underlying explicit memory storage in mammals. These will serve as useful points of comparison to consider similarities, differences, and still-existing limitations in our understanding of the functional significance of the structural synaptic plasticity recruited during the consolidation of both implicit and explicit forms of memory.