Distinct Contribution of Adult-Born Hippocampal Granule Cells to Context Encoding

Abstract

SUMMARY Adult-born granule cells (abGCs) have been implicated in cognition and mood; however, it remains unknown how these cells behave in vivo. Here, we have used two-photon calcium imaging to monitor the activity of young abGCs in awake behaving mice. We find that young adult-born neurons fire at a higher rate in vivo but paradoxically exhibit less spatial tuning than their mature counterparts. When presented with different contexts, mature granule cells underwent robust remapping of their spatial representations, and the few spatially tuned adult-born cells remapped to a similar degree. We next used optogenetic silencing to confirm the direct involvement of abGCs in context encoding and discrimination, consistent with their proposed role in pattern separation. These results provide the first in vivo characterization of abGCs and reveal their participation in the encoding of novel information.

Functional Imaging of Dentate Granule Cells in the Adult Mouse Hippocampus

“…Example movie of in vivo DG granule cell activity, corresponding to the recording shown in Figure 3A GCaMP6s for reporting action potential-evoked calcium transients has not been calibrated in DG granule cells so far, we cannot exclude that low-frequency baseline spiking remained undetected. Nonetheless, results obtained with both R-CaMP1.07 and GCaMP6s in anesthetized mice indicate very low spiking activity of adult granule cells, in agreement with previous reports that showed relative sparseness of DG activity using in vivo electrophysiological recordings and during in vivo imaging (Jung and McNaughton, 1993;Alme et al, 2010;Danielson et al, 2016).…”

“…These are exciting data that support the feasibility of chronic DG in vivo imaging. However, and in contrast to our approach that leaves the hippocampus intact, Danielson et al (2016) used a preparation that at least partially lesions hippocampal area CA1, which may substantially affect the functionality of hippocampal/EC circuitries (Bonnevie et al, 2013; Danielson et al, 2016). Be that as it may, the substantial rate of remapping of spatial representations (Bonnevie et al, 2013;Danielson et al, 2016) and the flexibility of granule cell activity in relation to behavioral-state preference (i.e., running vs resting) shown here both suggest that granule cell activation patterns in the adult DG change across days, presumably undergoing context-and experience-dependent plasticity.…”

“…Most recently, chronic imaging experiments of newborn and mature granule cells were described that found relatively high rates of remapping both in old and newborn granule cells when animals were exposed to different contextual experiences (Danielson et al, 2016). These are exciting data that support the feasibility of chronic DG in vivo imaging.…”

“…Through in vivo electrophysiological recordings and optogenetic silencing, the activity of dentate granule cells, the main excitatory neuronal cell population of the DG, has been associated with hippocampus-dependent behavioral pattern separation but also pattern completion Nakashiba et al, 2012;Neunuebel and Knierim, 2014;Danielson et al, 2016). These findings indicate a highly diverse contribution of granule cells to DG computation that appears to depend on the addition of newborn granule cells by neurogenic divisions of neural stem/progenitor cells that occurs throughout life in the mammalian DG (Clelland et al, 2009;Sahay et al, 2011;Spalding et al, 2013).…”

“…This is partly due to the lack of optical imaging methods for resolving granule cell activity within the intact hippocampal circuit in vivo, given that the DG is located several hundred microns deep below the ventral borders of the neocortex, which makes optical access to the DG difficult without interfering with or damaging overlying hippocampal structures. Consequently, DG granule cells have hardly been resolved structurally in vivo and have been imaged functionally in only one study so far (Gu et al, 2014;Kawakami et al, 2015;Danielson et al, 2016). Functional imaging of granule cell ensembles is, however, a prerequisite to further reveal fundamental principles of DG computation during encoding and expression of hippocampal engrams.…”