Hippocampal Granule Cells Opt for Early Retirement

The Kavli Institute for Systems Neuroscience, Centre for Biology of Memory, Norwegian University of Science and Technology, Trondheim, Norway.
Hippocampus (Impact Factor: 4.16). 10/2010; 20(10):1109-23. DOI: 10.1002/hipo.20810
Source: PubMed


Increased excitability and plasticity of adult-generated hippocampal granule cells during a critical period suggests that they may "orthogonalize" memories according to time. One version of this "temporal tag" hypothesis suggests that young granule cells are particularly responsive during a specific time period after their genesis, allowing them to play a significant role in sculpting CA3 representations, after which they become much less responsive to any input. An alternative possibility is that the granule cells active during their window of increased plasticity, and excitability become selectively tuned to events that occurred during that time and participate in later reinstatement of those experiences, to the exclusion of other cells. To discriminate between these possibilities, rats were exposed to different environments at different times over many weeks, and cell activation was subsequently assessed during a single session in which all environments were revisited. Dispersing the initial experiences in time did not lead to the increase in total recruitment at reinstatement time predicted by the selective tuning hypothesis. The data indicate that, during a given time frame, only a very small number of granule cells participate in many experiences, with most not participating significantly in any. Based on these and previous data, the small excitable population of granule cells probably correspond to the most recently generated cells. It appears that, rather than contributing to the recollection of long past events, most granule cells, possibly 90-95%, are effectively "retired." If granule cells indeed sculpt CA3 representations (which remains to be shown), then a possible consequence of having a new set of granule cells participate when old memories are reinstated is that new representations of these experiences might be generated in CA3. Whatever the case, the present data may be interpreted to undermine the standard "orthogonalizer" theory of the role of the dentate gyrus in memory.

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    • "The hippocampus and associated cortices are neural structures thought to be fundamentally involved in the learning and retention of facts, events and space in time (Alme et al. 2010; Buzsáki and Moser 2013). In mammals, the hippocampus is reciprocally connected, through the entorhinal cortex, to virtually all areas of the neocortex. "
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    • "Although it is possible to use an alternative IEG imaging approach more appropriate for the DG (Satvat et al., 2011), there are still important technical issues. For instance, electrophysiological data indicate that granule cells have sparse firing rates and that they can fire in multiple environments (Jung and McNaughton, 1993; Skaggs et al., 1996; Leutgeb et al., 2007; Alme et al., 2010). Importantly , very few granule cells (ϳ2%) are active during exploration to different environments (Chawla et al., 2005; Ramirez-Amaya et al., 2006, 2013). "
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    • "However, since the response speed ratio of inner to outer DG cells is roughly maintained in epileptic animals, it is possible that dentate function is maintained during ID scaling. Alternatively, or in addition, the ID regulation may be a molecular mechanism for the “early retirement” of DG cells (Alme et al., 2010). Accordingly one may formulate: faced with epileptic excitotoxicity, DG cells opt to retire, lose and survive, rather than to win and die. "
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