Role of dorsal and ventral hippocampal adult-born neurons in memory acquisition and recall




Huckleberry, Kylie Anne

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The hippocampus contains one of the few neurogenic niches within the adult brain—the subgranular zone of the dentate gyrus (DG)—and exhibits significant functional heterogeneity along its dorsoventral axis. As newborn neurons mature and integrate into the local circuit, they exhibit changes in connectivity and excitability. We were interested in the development of behavior-induced activity of adult-born neurons and whether that activity is necessary for learning. To investigate the development of activity, we characterized the expression of the immediate-early gene zif268 in mature and doublecortin+ (DCX+) immature neurons after exposure to a novel environment, an enriched environment, or water maze acquisition. Although all of the behavioral experiences increased zif268 expression in the mature neurons and 6-week-old mature adult-born neurons, behavioral experience unexpectedly suppressed zif268 expression in the DCX+ immature adult-born neurons. Because the DCX+ population ranges from 0-4 weeks of age, we characterized how zif268 expression changes over this period and found that behavior-induced zif268 suppression was specific to 3-week-old adult-born neurons. This suppression may support learning-induced apoptosis of immature adult-born neurons. To next address the requirement for the activity of adult-born neurons in learning, we used a Nestin-CreER(T2) mouse line to induce expression of the light-activated neural silencer Archaerhodopsin in neural progenitor cells and their progeny. Optical fibers were implanted into the dorsal or ventral DG to selectively silence adult-born neurons in those regions. Optogenetically silencing dorsal adult-born neurons impaired both acquisition and expression of context fear conditioning (CFC), but silencing ventral adult-born neurons impaired only expression of CFC. There was no effect of silencing adult-born neurons on the generalization of fear. Because silencing a small subset of adult-born neurons is sufficient to impair acquisition and expression of a fear memory, we hypothesize that adultborn neurons play a critical role in the acquisition and expression of fear memory. Moreover, we conclude that the dorsal and ventral adult-born neurons differentially contribute to acquisition and expression of memory. Overall, our data suggest that adultborn neurons are unlikely to be recruited into memory networks until they are at least 4 weeks old, at which point their activity is critical for memory.



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