Adult-Born Neurons in the Hippocampus Are Essential for Social Memory Maintenance

Abstract

Throughout adulthood, the dentate gyrus continues to produce new granule cells, which integrate into the hippocampal circuitry. New neurons have been linked to several known functions of the hippocampus, including learning and memory, anxiety and stress regulation, and social behavior. We explored whether transgenic reduction of adult-born neurons in mice would impair social memory and the formation of social dominance hierarchies. We utilized a conditional transgenic mouse strain (TK mice) that selectively reduces adult neurogenesis by treatment with the antiviral drug valganciclovir (VGCV). TK mice treated with VGCV were unable to recognize conspecifics as familiar 24 hr after initial exposure. We then explored whether reducing new neurons completely impaired their ability to acquire or retrieve a social memory and found that TK mice treated with VGCV were able to perform at control levels when the time between exposure (acquisition) and re-exposure (retrieval) was brief. We then explored whether adult-born neurons are involved in dominance hierarchy formation by analyzing their home cage behavior as well as their performance in the tube test, a social hierarchy test, and did not find any consistent alterations in behavior between control and TK mice treated with VGCV. These data suggest that adult neurogenesis is essential for social memory maintenance, but not for acquisition nor retrieval over a short time frame, with no effect on social dominance hierarchy. Future work is needed to explore whether the influence of new neurons on social memory is mediated through connections with the CA2, an area involved in social recognition. 3 Significance Statement Adult hippocampal neurogenesis has been implicated in behaviors linked to the hippocampus, including social behavior. We utilized a conditional transgenic mouse line to reduce adult-born neurons and explored social memory and social dominance hierarchy formation. We found that mice with reduced numbers of new neurons were unable to recognize conspecifics as familiar with a long delay after initial exposure but were able to recognize them as familiar with a short delay. We did not observe changes in social dominance as measured by home cage behavior or tube test performance in mice with reduced numbers of new neurons. These data confirm and extend previous reports to show that adult-born neurons are essential for maintenance but not for acquisition or short-term retrieval of social memories, nor for social dominance.

A Baldwin interpretation of adult hippocampal neurogenesis: from functional relevance to physiopathology

“…Thus, juvenile neurons have been shown to be important for the maturation of female-female social behavior as ablating DGNs from PND27 to PND35 decreased social exploration and time spent in close proximity with a conspecific, increased escape behavior, and impaired pup retrieval, all effects that were not seen after ablating Adu-DGNs [50]. As AHN has been involved in the maintenance of social memory [95][96][97], Juv-DGNs and Adu-DGNs neurons may actually play complementary roles in social behavior. In addition, we have shown that in contrast to Adu-DGNs, Neo-DGNs (PND7) are not recruited during spatial learning in the WM (or a dry maze where they learn to find a hidden food reward) but are activated when rats are learning to navigate through space in two different contexts [51].…”

Generation of an Lpar1-EGFP Fusion Knock-in Transgenic Mouse Line

“…However, the cell types responsible for these phenotypes are ambiguous. One attractive cell population for future studies is the mouse adult hippocampal precursor cell [92][93][94] that was reported to show high levels of LPA 1 expression based primarily upon the EGFP BAC mouse line created by the NIH GENSAT [95,96] project. This mouse showed high EGFP expression within white matter tracts like the Lpa 1 -EGFP mice reported here, but also showed high EGFP expression within the dentate gyrus [94] (and other locales such as the cerebral cortex) that did not overlap with the Lpa 1 -EGFP expression pattern.…”

Inhibiting adult neurogenesis differentially affects spatial learning in females and males

“…In our attempt to comprehensively survey the literature (Fig. 1), we counted only 4 functional studies that have reported data by sex or included sex as a variable in their statistical analyses (9,57,75,76).…”

“…Adult hippocampal neurogenesis has been implicated in many of the mnemonic functions of the hippocampus, including memory for temporal events (1-3), locations (4), contexts (5,6), objects (7,8) and conspecifics (9), as well as the consolidation (10,11) and forgetting (12) of memory. While spatial memory functions may be particularly apparent in conditions that maximize conflict or interference, such as when a goal changes location (13)(14)(15)(16), it is notable that many of studies have failed to find a role for new neurons in learning and short-term reference memory in the spatial water maze, a task that is highly sensitive to hippocampal disruption (2,6,7,(17)(18)(19)(20)(21)(22).…”