MemoryLoci · The Life Cycle of a Memory Trace: a New Understanding of Learning and Memory from Circuits to Synapses and Molecules

In MemoryLoci, we seek to understand the mammalian brain’s remarkable capacity to learn and remember. Episodic memory is central to most cognitive efforts and requires robust mechanisms to encode and retain salient features of our experiences while forgetting spurious details. What are the neural substrates of a memory trace, and how does the brain arbitrate among experiences for long-term storage? These central questions remain unresolved due to pervasive experimental roadblocks to our mechanistic understanding of the circuit-, cellular-, synaptic-, and molecular-level processes underlying information storage in the brain. Our groups have pioneered transformative approaches that now open the way to uncover the substrates of learning-related plasticity that support memory on scales from circuits to synapses and molecules. At the circuit level, we have innovated a method for indelible labeling of functionally identified memory-coding neurons in behaving animals, enabling correlated in-depth transcriptomic, molecular, physiological, and structural analyses of the functionally identified cells. At the synaptic-molecular level, we have pioneered all-optical approaches to directly interrogate synaptic plasticity and stability rules in behaving animals, followed by correlated molecular analysis of learning-related synaptic changes. We will integrate these foundational methodologies into a synergistic research program centered on the murine hippocampal circuit to decode the circuit, cellular, synaptic, and molecular logic of memory formation and retention. Our work will provide a profound understanding of how memories are formed and maintained in neural circuits. Thus, by establishing the circuit-, cellular-, synapse-, and molecular-level mechanisms of memory, our studies will revolutionize approaches to selectively modify the content of stored memories, which beckons new directions to treat memory pathologies in humans.