Stephen M. Stahl, M.D., Ph.D.
Issue: Neurotransmitters activate genes that activate other genes; that is, neurotransmission can rapidly deploy a strike force of immediate-early genes, like the first troops sent into combat. These early genes then combine to draft an army of genes to mobilize numerous important gene products that alter the function of a neuron targeted by a neurotransmitter.
|This is the fifth and final lesson in our series explaining molecular neurobiology for psychiatrists (see references 1-5). Previous lessons in this series have shown how neurotransmitters can quickly activate genes like c-fos and c-jun (Figure 1).3,4 These genes function as rapid responders to the neurotransmitter's input, like the first troops sent into combat once war has been declared. This rapid deployment force of immediate-early genes (IEGs) reacts within 15 minutes of receiving a neurotransmission (Figure 2) by being the first to encode their respective proteins, Fos and Jun. This encoding lasts for only a half hour to an hour, but it is enough time for Fos and Jun, nuclear proteins that live and work in the neuron's cell nucleus, to team up and form a leucine zipper-type of transcription factor. The zipper, in turn, activates many kinds of late-onset genes (Figures 1 and 2). Thus, Fos and Jun serve to wake up the much larger army of inactive genes. Which individual soldier genes are so drafted to active gene duty depends on a number of factors: which neurotransmitter is sending the message, how frequently it is sending the message, and whether it is working in concert with or opposition to other neurotransmitters talking to other parts of the same neuron at the same time.||
1. Stahl SM. Molecular neurobiology for practicing psychiatrists, part 1: overview of gene activation by neurotransmitters [Brainstorms]. J Clin Psychiatry 1999;60:572-573
2. Stahl SM. Molecular neurobiology for practicing psychiatrists, part 2: how neurotransmitters activate second messenger systems [Brainstorms]. J Clin Psychiatry 1999;60:647-648
3. Stahl SM. Molecular neurobiology for practicing psychiatrists, part 3: How second messengers "turn on" genes by activating protein kinases and transcription factors. [Brainstorms]. J Clin Psychiatry 1999;60:731-732
4. Stahl SM. Molecular neurobiology for practicing psychiatrists, part 4 [Brainstorms]. J Clin Psychiatry 1999;60:813-814
5. Stahl SM. Essential Psychopharmacology. 2nd ed. New York, NY: Cambridge University Press. In press