Grand Challenges of Neuroscience: Day 1

Following up on MC's posts about the significant insights in the history of neuroscience, I'll now take Neurevolution for a short jaunt into neuroscience's potential future.

In light of recent advances in technologies and methodologies applicable to neuroscience research, the National Science Foundation last summer released a document on the "Grand Challenges of Neuroscience".  These grand challenges were identified by a committee of leading members of the cognitive neuroscience community.

The document, available at, describes six domains of research the committee deemed to be important for progress in understanding the relationship between mind and brain.

Over the next few posts, I will discuss each of the research domains and explain in layperson's terms why these questions are interesting and worth pursuing.  I'll also describe potential experimental approaches to address these questions in a cognitive neuroscience framework.

Topic 1:  "Adaptive Plasticity"

One research topic brought up by the committee was that of adaptive plasticity.  In this context, plasticity refers to the idea that the connections in the brain, and the behavior governed by the brain, can be changed through experience and learning.  

Learning allows us to adapt to new circumstances and environments.  Arguably, understanding how we learn and how to improve learning could be one of the greatest contributions of neuroscience.

Although it is widely believed that memory is based on the synaptic changes that occur during long-term potentiation and long-term depression (see our earlier post) this has not been conclusively shown!

What has been shown is that drugs that prevent synaptic changes also prevent learning.  However, that finding only demonstrates a correlation between synaptic change and memory formation,  not causation. (For example, it is possible that those drugs are interfering with some other process that truly underlies memory.)

The overarching question the committee raises is: What are the rules and principles of neural plasticity that implement [the] diverse forms of memory?

This question aims to quantify the exact relationships between changes at the neuronal level and at the level of behavior.  For instance, do rapid changes at the synapse reflect rapid learning?  And, how do the physical limitations on the changes at the neuronal level relate to cognitive limitations at the behavioral level?

My personal opinion is that the answers to these questions will be obtained through new experiments that either implant new memories or alter existing ones (e.g., through electrical stimulation protocols). 

There is every indication that experimenters will soon be able to select and stimulate particular cells in an awake, behaving animal to alter the strength of the connection between those cells.  The experimenters can then test the behavior of the animals to see if their memory for the association that might be represented by that connection has been altered.


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  1. regarding your comment that changes in synaptic plasticity might not necessarily constitute the neural substrate of learning and memory, i would like to direct you to 2 science papers in the april 25th, 2006 issue. one is by mark bear, and the other is by charles sacktor. together, they provide a reasonably direct demonstration that changes in synaptic strength actually do indeed underlie learning and memory (at least one form, anyway). there are numerous other studies that address this indirectly, some of which, as you point out, rely heavily on pharmacology, which is obviously going to have side-effects and be correlational. however, these studies, and others, are consistent with what has been observed using genetic techniques, which of course have their own sets of problems. but the convergence between the sets of approaches, and the 2 science papers, i think put the field beyond the stage at which you characterize it.

    while the hope is of course to directly manipulate single cell neural activity and thus plasticity in awake behaving animals, i suspect that a reliable and believable result in this area is going to be a long time coming. while we can certainly do in vivo patch clamp currently, and maybe even start to manipulate neurons with light via ChR2 or other photopigment-channels, i think its going to be tough to get from the single cell spiking level in primary sensory cortex up to showing some sort of behavioral result. we’ll have to see. implanting memories or deleting them based on single cell or even single synapse activity is going to very hard, if not impossible in the near term, but i totally agree that this is where we should be headed.

  2. Mark- Thanks for contributing your comments. I agree with you that there’s a lot of good reason to believe that we have in fact determined the neurobiological underpinnings of memory.

    I would be very interested in checking out the two science papers that you mentioned but I haven’t been able to locate them either through the website (there doesn’t seem to be an April 25, 2006 issue of Science) or through Google Scholar. Any additional information on these articles or complete references would be really great.

  3. While science remains stuck in disproven Descartian / Newtonain model of the universe, memory will remain forever elusive.

    The buring question is where are the memories?

    How is it that Fernch word not used in 40 years when needed is there immediately.

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