Synaptic Tagging and Metaplasticity as Mediators of Neuronal Consciousness

Forming memories for highly arousing, novel, or salient events engages synaptic mechanisms that allow the association of temporally remote events and details. In the preceding version of this chapter, we argued that these experiences recruit metaplasticity and synaptic tagging processes, increasing both synapse plasticity and neuronal sensitivity to incoming inputs. During this heightened state of “neuronal consciousness,” the synaptic representation and association of events separated in time are enhanced, providing a means for increasing the qualitative aspects of a given memory. These processes (synaptic tagging, metaplasticity) likewise incorporate the key element of time, allowing neurons to detect and integrate temporally separated events. By extending the time frame in which events can be associated at a synaptic level and biasing synapses toward a plasticity-conducive state, synaptic tagging and metaplasticity provide potent mechanisms for enhancing memory quality in the brain. Through preparing or “priming” synapses for future encoding, metaplasticity serve as a gateway for augmenting neuronal consciousness. Priming lowers the threshold for neuronal detection and synaptic encoding of salient future events. This process is complemented by synaptic tagging, which provides an elegant means for associating “strong” and “weak” stimuli, facilitating storage of detailed memories. We review key intracellular signaling mechanisms that initiate lasting changes in the ability of synapses to undergo metaplasticity, along with leading candidate synaptic tags that facilitate metaplasticity. We also speculate on how these phenomena bolster neuronal consciousness to sculpt the brain’s capacity to dynamically encode and store information. This chapter is dedicated to Dr. Peter V. Nguyen, a pioneer in the study of many forms of noradrenaline-mediated synaptic plasticity.