This posting is in response to a recent new snapshot we highlight the brain plasticity research of Michael Greenberg (Harvard). In that news clip we noted that “The mechanisms that are responsible for brain plasticity, learning, are considered to be the number one problem in the study of how our minds work. The recent work of the Harvard neuroscientist Michael Greenberg illustrates how far we have come at identifying the fundamentals of how experience affects brain growth and development. His work and that of other neuroscientists has identified, at a molecular level, the underlying mechanisms of brain plasticity including how genes are turned on as a result of experience. So when we think of leaving a record of experience in memory we are not only c0nsidering the chemistry of how neurons communicate with one another but also the genetic events that activated within a cell.”
We asked the noted NIH geneticist Joni Rutter geneticist several questions about the genetic story behind brain plasticity.
GK questions to JR start with:
GK: What are the consequences of gene activation….i.e., in processing information…or memory.,…or anything else about the life of a cell? …and
What might be some of the implications of gene activation for understanding how minds work?
JR: There are two questions here. The first one I will re-phrase: what happens when a neuron vs. a liver cell is activated by the same stimulus?
Since a neuron is different from a liver cell even though they have the same exact DNA, they are able to respond to various stimuli in different ways. A stimulus will activate particular receptors, which in turn will activate particular signaling pathways. The genes in the nucleus are activated (or repressed) depending on the abundance of proteins in the cellular milieu that are involved in propagating the signaling pathways. The nuclear transcription factors that are recruited to bind to the DNA to turn on or turn off gene transcription are different in different cell types. Transcription factors that get stimulated in a liver cell may bind to DNA to activate genes involved in metabolism of the stimulus that activated the cell in the first place, while a neuron activated by the same stimulus may cause transcription factors to bind to DNA that may turn on or off genes that make serotonin receptors in response to the stimulus. So, the same stimulus can cause different genes to be turned on depending on the cell type that was exposed.
The second question—is gene activation an expected result of neuron stimulation?
Upon neuronal stimulation, signaling pathways ultimately activate transcription factors or other proteins (through chromatin modification or through DNA methylation, for example) that modify DNA to alter gene expression. Through these mechanisms, genes can either be activated or repressed depending on the stimulus. There is a good deal more to say here and I will do so in a later correspondence.
GK: What are the consequences of gene activation….i.e., in processing information…or memory.,…or anything else about the life of a cell? …and
What might be some of the implications of gene activation for understanding how minds work?
JR: Questions 2 and 3 are similar so I will answer them together.
Rather than gene activation per se, I’ll refer to it as gene expression changes, since we know that genes can be turned off or turned on. Gene expression changes can cause an increase in receptor expression, decreased receptor expression, changes in abundance of signaling molecules, etc. These changes in protein expression for a given neuron in the brain can cause changes in how the brain cells respond to their environment, and how they communicate with their neighboring cells. For example, drugs of abuse are known to act on cells in the frontal cortex, and cause many changes in gene expression that effectively hi-jack the normal signaling pathways in the cell. In doing so, the mind becomes crippled because signaling across synapse in the frontal cortex may become dysregulated—sort of like short-circuiting the signals.
GK: Finally, what might be some of the implications of gene activation for understanding how minds work?
JR: Wow …..Now that question has huge implications and I need more time to respond. You can post what I have to say later.
I (GK) have a few final thoughts about what you (JR) have told us. First of all we need to know and learn much more about neurobiology and genetics to appreciate what you have told the activation of neurons and the role of genetics. Even simple excellent explanations cannot transcend a lack of basic science knowledge. Our workgroup must continue to be patient and learn. After we have put in our homework we can come back to you for a second take on the questions we have explored here.