The dentate gyrus (DG) is crucial for our ability to discriminate similar memories, and it is thought to do so by a process called pattern separation. Pattern separation is the computation that makes the outputs of a system less similar than its inputs. The neural discharge of DG place cells signals cell-specific locations and DG place cells change their location-specific firing (“global remapping”) and/or firing rate (“rate remapping”) as if to discriminate similar environments, and this occurs more so than place cells in downstream hippocampus subfields CA3/1. Consequently, the prevailing assumption posits that remapping is the neural mechanism underlying memory discrimination but the critical experiment linking remapping to memory discrimination was never performed.
First, this dissertation demonstrates in mice, that optogenetic inhibition of mature or immature DG granule cells is sufficient to impair memory discrimination and cognitive flexibility using the active place avoidance (APA) task, confirming the task is sensitive to DG-dependent memory discrimination. Next, it was confirmed that DG place cells remap across similar environments and that DG place cells are more sensitive to changes in the environment than downstream CA1/3 regions, as previously reported. These results provided the opportunity to perform the critical experiment to test whether remapping underlies memory discrimination. Single unit spike trains were recorded from DG place cells while mice perform the DG-dependent memory discrimination APA task. Contrary to the prevailing assumption, it was found that DG place cells do not remap across spatial tasks that require DG-dependent memory discrimination. Instead of remapping, place-discriminating discharge is observed transiently amongst DG place cells, particularly where memory discrimination is most necessary. To signal memory discrimination, DG place cells express distinctive sub-second network patterns of co-firing. This is accompanied by increased coactivity of discharge between excitatory place cells and inhibitory interneurons specifically when memory discrimination is successful. Instead of remapping, these findings identify that memory discrimination is signaled by sub-second patterns of correlated discharge within the dentate network.
By emphasizing the role of neural dynamics to assess cognitive operations like memory discrimination, this work demonstrates the importance of new analysis methods that are crucial to rigorously examine hippocampal network dynamics. By critically testing and rejecting a long posited, but never tested hypothesis, this work advances the hippocampal memory field, demonstrating that in addition to the steady-state tuning of neural discharge, successful memory operations are associated with transient, sub-second changes in how multiple neurons synchronize and desynchronize their discharge.
|Advisor:||Fenton, Andre A.|
|Commitee:||Alberini, Cristina, Buzsaki, Gyorgy, Davachi, Lila, Scharfman, Helen|
|School:||New York University|
|Department:||Basic Medical Science|
|School Location:||United States -- New York|
|Source:||DAI-B 79/12(E), Dissertation Abstracts International|
|Keywords:||Dentate gyrus, Memory discrimination, Pattern separation, Place cells|
Copyright in each Dissertation and Thesis is retained by the author. All Rights Reserved
The supplemental file or files you are about to download were provided to ProQuest by the author as part of a
dissertation or thesis. The supplemental files are provided "AS IS" without warranty. ProQuest is not responsible for the
content, format or impact on the supplemental file(s) on our system. in some cases, the file type may be unknown or
may be a .exe file. We recommend caution as you open such files.
Copyright of the original materials contained in the supplemental file is retained by the author and your access to the
supplemental files is subject to the ProQuest Terms and Conditions of use.
Depending on the size of the file(s) you are downloading, the system may take some time to download them. Please be