Brain gene powers ... activate!

A literature search for another topic brought me this article from 2004 by Suk Jin Hong and colleagues (Johns Hopkins):

Identification and analysis of plasticity-induced late-response genes
The excitatory neurotransmitter, glutamate, activates N-methyl-D-aspartate (NMDA) receptors to induce long-lasting synaptic changes through alterations in gene expression. It is believed that these long-lasting changes contribute to learning and memory, drug tolerance, and ischemic preconditioning. To identify NMDA-induced late-response genes, we used a powerful gene-identification method, differential analysis of primary cDNA library expression (DAzLE), and cDNA microarray from primary cortical neurons. We report here that a variety of genes, which we have named plasticity-induced genes (PLINGs), are up-regulated with differential expression patterns after NMDA receptor activation, indicating that there is a broad and dynamic range of long-lasting neuronal responses that occur through NMDA receptor activation. Our results provide a molecular dissection of the activity-dependent long-lasting neuronal responses induced by NMDA receptor activation.

As you might predict from the prose, this is a pretty technical paper: all about microarrays and upregulation. But there is some very interesting stuff in here.

First, the study looked for late response genes: those who showed changes in expression between 6 and 24 hours after the stimulation of the NMDA receptors. NMDA glutamate is a neurotransmitter; brain researchers have studied it because it appears to play an important role in the survival of neurons, and problems with NMDA signalling are associated with neuron damage after a stroke. By looking for late responses, the study was attempting to identify the genes that might be involved in neuron growth, including the strengthening of connections between neurons. These changes are necessary for learning, memory, and other so-called "plastic" responses in the nervous system.

So in other words, this is an attempt to find some of the genes that allow our brains to change. The research was done with rat brains.

The study found hundreds of genes (661, to be exact) that are up-regulated late after NMDA receptor stimulation. Up-regulation means that the genes are producing mRNA transcripts in greater numbers than without the stimulation. According to the paper, this number excludes those genes that produce only immediate effects but return to baseline levels by 6 hours. It includes over 150 previously unidentified genes.

This is too many genes to find a clear pathway for neuronal changes, at least not yet. But it shows that neurotransmitters exert lots of changes on neurons. Many of them certainly cause dendrite growth, alterations in synapse sensitivity, production of more (or less) receptors, and other changes.

And all of these are possible targets of selection in human evolution. Culture and learning are incredibly important to human behavior, and our brains do not develop normally in the absence of cultural and other environmental stimuli. Thus, culture cannot involve merely intrinsic structural genes. It must influence brain structure via hormonal and neurotransmitter pathways. The responses to these culture-mediated influences must be among the most important determinants of what makes us human.

References:

Hong SJ, Li H, Becker KG, Dawson VL, Dawson TM. 2004. Identification and analysis of plasticity-induced late-response genes. Proc Nat Acad Sci USA 101:2145-2150. Free full text online