On Tuesday night, I headed down to the beautiful Bell House in the Gowanus section of Brooklyn, for the latest Secret Science Club lecture, by NYU neurobiologist and biomedical engineer André Fenton, who studies the "mechanics" of memory. Besides his academic endeavors, Dr Fenton started the Biosignal Group, which produces a miniature, wireless EEG monitor.
Dr Fenton started his lecture with a quote by Gautama Siddhartha: "All that we are is the result of what we have thought. What we think, we become."
Memory is characterized by "truthiness", memories have a certain "fuzziness" about them. Memory doesn't function like a recording device, it is a reconstructive process, not a reproductive process. Basically, we make up stories... memories are created out of what we expect of the world, not necessarily what happened. We even remember events that never happened. Dr Fenton illustrated this with a memory test in which words such as "bed", "slumber", and "wake" were flashed briefly on a screen, and the audience was quizzed afterword about which words had appeared in the test. A good portion of the audience misremembers the word "sleep" as having appeared, while a word such as "horse" is not falsely remembered.
After this brief illustration of the nature of memory, the talk proceeded to the biology of memory- how does memory work in the brain, and where in the brain should we start to look? The best estimate is that the human brain contains about 100 billion neurons. Each neuron is a "chemical factory" and the interaction of these chemicals have electrophysiological effects. The brain is an electrical organ, neurons send electrochemical signals. To illustrate the connection between neurons, and the role that synapses play in the formation of memory, Dr Fenton showed us a film of the firing of a single entorhinal neuron in the brain of an epilepsy patient who had had electrodes implanted into his brain as a therapeutic measure. The patient was shown various images, and this particular neuron was most active while the patient was shown "Simpsons" clips and while recollecting said "Simpsons" clips. It would seem that single neurons are tuned to particular features of the outside world.
As an example of such "tuning", Dr Fenton cited head direction cells, discovered in Brooklyn, which activate when a rat's head is facing in a particular direction. As another example, place cells activate when a subject is in a particular location. It's important to note that there are no sense organs for place or orientation, so a calculation must be made. Dr Fenton compared this process to a whole "symphony" of cells being active in sense of place, movement, and orientation. The business, and joy, of neuroscience is figuring out how this symphony works.
Dr Fenton then moved on to the topic of synapses, the contacts between neurons- synaptic connections are the fundamental property of neurons. Cognitive experiences leave a lasting imprint within synapses. Experience and other electrochemical relationships "tune" synapses, they set synaptic relationships and maintain them. As Guatama Siddhartha put it, experiences define who you are and who you are going to be.
In studying the anatomy of the brain, experiments on humans is unethical (again, the subject in the aforementioned "single neuron" experiment had had electrodes implanted for therapeutic reasons related to a severe case of epilepsy). As an aside, these ethical standards may be different in the antipodes. Rats and mice are the typical subjects in brain anatomy studies.
Anatomically, the region of the bain most involved in memory is the hippocampus. In the hippocampus, neurons form circuits for information flow and transformation. In an aside, Dr Fenton imparted to us an important life lesson: TRY NOT TO DAMAGE YOUR HIPPOCAMPUS. Dr Fenton then showed us an image of the hippocampus of a mouse which had been genetically engineered so that the neurons produced a protein which made them glow green when active, the image was similar to this. Images of the signals across the synapses shows the organization in the synapses. Information is created, organized, and stored in the synapses as far as we understand. As far as the long-term retention of information, changes occur in the strength of relationships between synapses. Dr Fenton expressed this in a simple, cute and (importantly) memorable fashion: Neurons that fire together wire together.
The next topic was the brain's ability to change despite the limitations of anatomy. Changes in brain activity are dependent on synaptic plasticity. Coincident activation changes synapses- if enough of a chemical is released in a reliable way, subsequent activation is easier.
In a droll aside, Dr Fention informed that audience that "stimulates" is a fancy word for "electrocutes"- stimulating neurons electrically creates a response and rapid stimulation makes the response bigger. Change is important and can be regulated, high frequency stimulation makes a response bigger, and the response remains bigger because of brain changes.
One particular chemical which plays a role in memory is protein kinase M zeta. For more information on PKM zeta, Ed Yong has several relevant blog posts. Experiments demonstrated that the actions of protein kinase M zeta could be inhibited through the use of another protein, zeta inhibitory peptide. Zeta inhibitory peptide undoes the strengthening of synapse sets, in effect resetting the relationship to a "baseline" level. Injecting zeta inhibitory peptide into rats makes even "educated" rats act as if they were naive- in effect, it "erases" memory. Dr Fenton noted that memory is not everything, how one uses memory is also important (I sure hope that using memory to blog about lectures on memory is a worthy use of memory).
Inquiries into how cognitive experience changes the brain involve such questions as: Where is the PKM zeta molecule made? Where does it go? Where in the brain is PKM zeta present? Mice are used as the subjects in theser experiments because their genome is better known and more easily manipulated than that of rats. Trained mice have more PKM zeta present in their brains than untrained mice, and the difference in how much PKM zeta is present in different synapses makes the organization of these synapses apparent. The functional changes are not only due to the fact that the protein is present, but also due to the fact that it changes the synapses- measurement of electrical activity in the brain shows that trained animals produce different signals than animals in an untrained control group. These differences are attributed solely to prior experience. One finding that could have potential therapeutic use is that the manipulation of experience made changes can mitigate brain damage.
Preemptive cognitive experience has the power to change brain and psychological function. To illustrate this, Dr Fenton showed us Sandro Del-Prete's Message d'Amour des Dauphins:
Experience determines how one interprets the world- while it may take a while for you dirty dogs to see the dolphins in the image, a five year old would probably spot them immediately.
The lecture then moved on to possible therapeutic implications of training. Cognitive control is the ability to coordinate the use of information from multiple sources, typically for optimizing actions. Mental illness impairs cognitive control, the basic challenge in psychiatry is to improve cognitive control in patients. Optimal outcomes depend on context, a determination must me made of which information is most relevant in any situation. To illustrate this, Dr Fenton subjected the audience to a Stroop test:
A Stroop test was developed for rats and it was determined that brain-damaged rats had difficulty with the test. The brains of the rats were lesioned in such a way as to mimic schizophrenia, which may be triggered by fetal trauma. The schizophrenic rats had problems recognizing the incongruent stimuli presented in the Stroop test. Cognitive training during adolescence was able to prevent these deficits... early cognitive training may be able to mitigate brain damage. The adolescent cognitive experience prevented the adult cognitive control deficit despite persistent brain damage- the syanpses were "tuned" by training. Early cognitive experience promotes normal brain function- a normal brain is well synchronized, and early cognitive training makes synchronization easier and promotes plasticity. Experience tunes the synaptic communication pathways that create and control information flow through the brain. Cognitive experience in adolescence may be the "therapeutic window" to manipulate the brain in order to mitigate damage.
Dr Fenton then briefly discussed the ethics of prophylactic measures- while he was dubious about the ethics of prophylactic medication, he indicated that cognitive behavioral therapy would be a better therapeutic technique. The inability to focus mentally is debilitating, and cognitive training can mitigate this problem.
In the Q&A, some bastard in the audience was going to ask Dr Fenton if there were different biological mechanisms for short and long-term memory, but some evil mother pre-empted him (just kidding, no offense- the bastard had a sore throat anyway, so he wasn't prepared to bellow anyway). Dr Fenton answered that there was no evidence that different processes were involved.
Once again, the Secret Science Club dished out a, heh heh, memorable lecture. This particular lecture hit that sweet spot at the intersection of hard science, human interest, and social relevance. Bravo SSC and Dr Fenton! For a taste of this lecture, here is a "Studio 360" presentation by Dr André Fenton:
If you pour yourself a drink before hitting play, you'll have some approximation of the awesome power of the Secret Science Club.