Arc And Cellular Reactivation

and Bruce McNaughton has demonstrated that Arc regulation is particularly interesting, and we will return to these studies in later chapters. Of course, in order to make an active product, all genes must be transcribed, processed into mRNA, and then translated into protein. Arc mRNA has the interesting attribute that it is rapidly transported into dendritic processes. In fact, the mRNA is selectively transported and compartmentalized to dendritic regions that have undergone recent excitation. There it participates in local protein synthesis, the net result of which is selective localization of Arc protein at synapses experiencing recent activity.

Like many other IEGs, Arc transcription is regulated in the brain in response to various types of environmental stimulation. Arc transcription is increased in specific pyramidal neurons in area CA1 within a few minutes of exploration of a novel environment (see, for example, reference (31). This is most likely a molecular correlate to increased place cell firing and the establishment of place fields in hippocam-pal pyramidal neurons. In a study that combined molecular biology approaches with behavior, Guzowski et al. (31) capitalized on neuronal activity-dependent Arc expression to demonstrate that the same hip-pocampal pyramidal neurons that fire initially when place fields are established also fire when the animal is re-placed into the same context. In these studies Guzowski et al. used Arc as an activity-dependent molecular marker to track the activity of specific ensembles of pyramidal neurons over time, an elegant application of molecular approaches in the context of the behaving animal.

BOX 1 For legend see opposite page.

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