How does synaptic plasticity support memory formation?

Synaptic mechanisms

Synaptic plasticity refers to the activity-dependent strengthening or weakening of connections between neurons, and it is the cellular foundation for many forms of learning and memory. Long-term potentiation and long-term depression were first characterized by Terje Lømo and Timothy Bliss at the University of Oslo, who showed that brief, high-frequency stimulation produces a long-lasting increase in synaptic efficacy. Subsequent work by Graham Collingridge at the University of Bristol clarified that NMDA type glutamate receptors act as molecular coincidence detectors that permit calcium entry only when presynaptic release and postsynaptic depolarization coincide, initiating intracellular cascades that alter receptor trafficking and synaptic strength. Eric R. Kandel at Columbia University extended these findings in simpler circuits of the sea slug Aplysia, demonstrating that short-term synaptic changes rely on modification of existing proteins while consolidation into long-term memory requires new gene expression and protein synthesis; this body of work underpinned Kandel’s Nobel Prize in Physiology or Medicine.

Synaptic plasticity includes both functional and structural changes. Functional potentiation can result from insertion of AMPA receptors into the postsynaptic membrane; structural plasticity often involves the growth or retraction of dendritic spines, observed with high-resolution imaging techniques. These coordinated molecular and morphological changes allow a distributed neural network to store information by selectively strengthening pathways that represent repeated or salient experiences.

Causes, consequences, and contextual influences

Patterns of activity such as repeated practice, salient emotional events, and sleep-dependent replay drive the processes that stabilize synaptic changes. Richard G. Morris at the University of Edinburgh provided influential evidence linking NMDA receptor–dependent plasticity in the hippocampus to spatial learning, showing that pharmacological blockade of these receptors impairs performance in spatial navigation tasks. Sleep plays a consolidating role; Matthew Walker at the University of California Berkeley has summarized how stages of sleep promote transfer and integration of hippocampal-dependent memories into cortex, stabilizing synaptic changes formed during wakefulness. Conversely, chronic stress alters plasticity in the hippocampus and prefrontal cortex, a phenomenon documented by Bruce S. McEwen at Rockefeller University, with consequences for learning, decision making, and emotional regulation.

At the population level, synaptic plasticity shapes cultural and territorial behaviors. Educational practices that emphasize spaced repetition and retrieval exploit plasticity principles to enhance durable learning. Environments that reduce chronic stress and improve sleep support healthier neural remodeling and memory retention across communities. Pathologically, impaired synaptic plasticity is a hallmark of neurodegenerative and psychiatric conditions, where synapse loss or maladaptive strengthening underlies cognitive decline and maladaptive behaviors, making synaptic mechanisms a central target for therapeutic strategies.

Understanding how synaptic plasticity supports memory formation connects molecular neuroscience to real-world outcomes. By tracing mechanisms from receptor kinetics to network remodeling and by examining how lifestyle, stress, and sleep modulate these processes, research led by investigators at institutions such as the University of Oslo, the University of Bristol, Columbia University, the University of Edinburgh, the University of California Berkeley, and Rockefeller University provides a coherent, evidence-based framework for improving learning, treating disease, and shaping environments that foster healthy cognitive function.