Leading researchers from around the world present their latest research into the neuroscience of memory at New York University.
Neuron by neuron, we snap together mental structures, constantly evolving palaces of memory that we carry with us until we die.
– George Johnson, In the Palaces of Memory
As we move through the world, our senses measure the raw data of our experience: a touch is registered by slight changes in pressure on our skin’s surface; a shrill siren rattles the hair cells within our ears. We experience our environment through these physical interfaces—and, like a sponge onto water, we soak up this raw data for everything it’s worth. From the moment our nervous system coalesces, we measure the world with these evolved systems so that we can begin to predict its tendencies and find useful patterns amid the chaos.
Far from storing individual memories in individual cells, the picture of memory in the brain that has emerged in the last half-century of active research is one of a widely distributed and dynamic system involving networks of neurons throughout the brain. In the mid-20th century, Donald Hebb set forth the influential idea that cells which fire together will wire together; Eric Kandel’s Nobel Prize-winning research in the 1960s illustrated the beautiful symphony of neurotransmitters and proteins on the cellular level that accounts for these experience-based changes to the physical structures of the brain—the gradual remodeling of our palaces of memory.
Now, as we face this 21st century of ever-intensifying research into the central nervous system, memory—like consciousness and sleep—remains one of the essential questions about the brain. How, on the most basic levels, does a constellation of cells and synapses store a lifetime of information? What are the mechanisms that cause memories to fade, shift, or be rewritten over time? How much sleep do I need tonight to remember writing this tomorrow?
This past weekend, some of the leading memory researchers from around the world gathered at New York University for a two-day symposium entitled “The Mysteries and Marvels of Memory,” hosted by the NYU Center for Neural Science. Assembling the experts into thematic triads with twenty-five minutes allotted for each presentation, the organizers smartly moved the program from presentations on Saturday morning about the “building blocks of biological learning machines” to more specialized avenues of research into memory erasure, long-term storage and retrieval, and functional localization of memory in the hippocampus and other structures in the brain as presented in Sunday’s talks.
As all investigations of complex biological systems evolved over millions of years should, Seth Grant of the Sanger Institute in Cambridge began the symposium with a riveting exploration of “The Origins of the Synapse and Evolution of Adaptive Behavior.” According to his research, we should think of the brain as a structure that evolved millions of years earlier than we currently believe, with primitive organisms containing proteins and molecular arrangements that Grant’s genomic research indicates were precursors to the synapse. These primitive systems were scaled up to form the complex nervous systems we now call a “brain.” His talk helped to cement the idea that our vastly complex nervous system grew from very simple structures that evolved for basic solutions to tractable environmental pressures. We must understand that there is a “deep ancestry of synaptic evolution,” as Grant put it.
Henry Markram, director of The Blue Brain Project at EPFL in Lausanne (and whom I’m working with on a 10-year documentary film project), followed with a whirlwind tour through his latest research into the balance of nature versus nurture on the level of neurons and synapses. Markram is using multicellular patch-clamp recording techniques to measure the activity of up to twelve cells at once, allowing him and his team to grasp, with increased resolution, the role of these cells with within a larger network. The take-home message is that we should perhaps think more about the dynamics at the synapse and less about the constant branching of axons and shifting of cellular structures when it comes to memory. The brain, with its vast networks of interconnected neurons, may be more hard-wired than we often believe, with slight modulations to chemical release accounting for the storage of experience more so than the dramatic reshaping and extension of axons to connect with new cells every time a memory is formed.
Moving from the extreme bottom-up approach to one focused on behavior as well as cells, Joseph LeDoux’s talk, entitled “Building Blocks of the Fear Learning Machine,” related the latest insights from his research into the structural underpinnings of fear and memory in the brain (we previously profiled LeDoux’s research into emotional memory and fear learning here), which continue to suggest that memory is much more dynamic and flexible than once thought—updating, revising, and re-filing of memories are processes that LeDoux’s talk as well as a bevy of other researchers at the symposium handled in neuroscientific terms.
Marie Monfils, who once worked in LeDoux’s lab, presented new work from her UT Austin lab, where she is investigating the interaction of reconsolidation and extinction in fear memory. Some of the latest insights from LeDoux, Monfils and others concern the process of bringing a stored memory back into conscious awareness so that it can be “updated” and sent back into storage, re-colored (hopefully for the better, in the case of traumatic memories) so that next time it’s hauled out of the closet it feels nicer to put on. The esteemed researcher Yadin Dudai, who gave the keynote address for the symposium entitled “The Engram Shaped and Reshaped: Lessons from the Rat Neocortex,” may have put it best: “The best memory is the memory you never use. Once you use it, it becomes unstable.”
This research could have significant clinical implications– but the symposium made it clear that more work needs to be done before we can tease out any such approaches to the vast and tangled system that is memory in the brain. Todd Saktor of SUNY Downstate Medical Center presented intriguing research into the activity of PKM, a protein which acts as a sort of housekeeper to aid in the storage of long-term memory in the brain, maintaining the synapses that link together the constellations of cells that encode our past experiences (for more, see this article about a study involving PKM).
Saktor and others are interested in what happens when PKM is inhibited, thus preventing the normal levels of housekeeping in networks of memory-encoding neurons. In the work done so far, there is promising evidence that blocking PKM seems to effectively erase certain memories in animal models by letting synapses fade into inactivity. This research, combined with new insights into other drug agents such as Propanolol that modulate fear memory, suggests that clinical applications of these new avenues of memory research–perhaps even for PTSD– may be approaching in the years to come.
In similar lines of research, Sheena Josselyn of the University of Toronto spoke of the need to find “the bare minimum of neurons needed to encode a fear memory” in order to finally define an engram; Bong-Kiun Kaang of the Seoul National University gave a talk entitled “Dynamic Nature of Long-term Memory” that elegantly moved between explanations of protein degradation and the degradation of long-term memories stored within these networks of proteins, cells and synapses. On Sunday, speakers shifted to considerations of larger structures and behavioral applications of memory research: Charan Ranganath of UC Davis spoke of research into improving episodic memory through behavioral training, and others spoke to new findings about the hippocampus, a key control center of all memory systems in the brain.
Paving the road from behavior to cellular structures and back again is a pursuit that linked all the talks at the symposium, and will surely continue to be the singular goal of this developing field. On the whole, the research continues to point to the flexibility and widely distributed nature of memory. Like steam rising through a house, our experiences come to fill the complex chambers of our brain throughout our lives, billowing about in every conscious moment and subject to constant rearrangement, re-emergence, and dissipation. One day we may be able to use new techniques to erase the unwanted, ensure the consolidation of the necessary, and re-color the pained. But perhaps the best thing we can do for now is try to get eight hours of sleep.