Researchers from the State University of New York have identified a pivotal compound that helps shape long-term memories in the brain. The finding, published in Science Advances, broadens our understanding of how memories are formed and stored over time.
Memory formation begins in the hippocampus, a brain region where networks of neurons become activated when a person experiences something meaningful. Each subsequent recollection tends to reactivate the same neural ensemble. When one neuron repeatedly triggers another, the connection between them strengthens. This synaptic reinforcement, occurring across the hippocampus and involving other brain regions, transforms fleeting experiences into lasting memories.
For long-term storage, brain cells produce specific proteins that bolster the wiring between neurons. Among these, the enzyme PKMzeta stands out as a constant producer in neurons, yet the mechanism guiding PKMzeta to the right synapses remained unclear until now. Researchers traced a molecule named KIBRA, which appears to recruit PKMzeta to particular synaptic sites, effectively guiding the memory-formation process.
In this study, KIBRA is described as acting like a molecular glue. It binds to strong synapses and concurrently directs PKMzeta to those same connections, providing a plausible explanation for how memories are selectively stabilized. This dual role helps illuminate why certain synapses become preferentially strengthened during learning and memory consolidation. [Citation: Science Advances, 2023]
To test the functional relevance of the KIBRA-PKMzeta interaction, the team carried out animal experiments to assess how disrupting this partnership would affect memory performance. Mice with impaired communication between KIBRA and PKMzeta demonstrated deficits in long-term spatial memory. In practical terms, they were less able to avoid areas in a testing arena where previous shocks had occurred, indicating a diminished ability to remember the locations associated with danger. These results underscore the importance of the KIBRA-PKMzeta axis in maintaining robust, lasting memory traces. [Citation: Science Advances, 2023]
Beyond the basic science implications, researchers are hopeful this line of inquiry may inform future strategies for treating memory-related disorders. Alzheimer’s disease and other conditions characterized by memory decline could potentially benefit from interventions that enhance or mimic this molecular targeting mechanism. Early work suggests that stabilizing memory-related synapses through precise protein interactions might slow the progression of memory loss or improve cognitive resilience. [Citation: Science Advances, 2023]
While previous studies have explored ways to counter memory decline using experimental compounds, the new findings provide a clearer map of the cellular machinery involved. By identifying KIBRA as a key partner that guides PKMzeta to strong synapses, scientists gain a more concrete target for developing therapeutics aimed at preserving long-term memories and slowing neurodegenerative processes. This research adds a promising piece to the larger puzzle of how memories are formed, stored, and retrieved in the aging brain. [Citation: Science Advances, 2023]