Pattern separation in the hippocampus: distinct circuits under different conditions

Abstract

Pattern separation is a fundamental hippocampal process thought to be critical for distinguishing similar episodic memories, and has long been recognized as a natural function of the dentate gyrus (DG), supporting autoassociative learning in CA3. Understanding how neural circuits within the DG-CA3 network mediate this process has received much interest, yet the exact mechanisms behind remain elusive. Here, we argue for the case that sparse coding is necessary but not sufficient to ensure efficient separation and, alternatively, propose a possible interaction of distinct circuits which, nevertheless, act in synergy to produce a unitary function of pattern separation. The proposed circuits involve different functional granule-cell populations, a primary population mediates sparsification and provides recurrent excitation to the other populations which are related to additional pattern separation mechanisms with higher degrees of robustness against interference in CA3. A variety of top-down and bottom-up factors, such as motivation, emotion, and pattern similarity, control the selection of circuitry depending on circumstances. According to this framework, a computational model is implemented and tested against model variants in a series of numerical simulations and biological experiments. The results demonstrate that the model combines fast learning, robust pattern separation and high storage capacity. It also accounts for the controversy around the involvement of the DG during memory recall, explains other puzzling findings, and makes predictions that can inform future investigations.

Gain‐Loss Framing Enhances Mnemonic Discrimination in Preschoolers

“…The author suggested that this facilitation in pattern separation for items encoded during threat might be mediated by noradrenergic activity during encoding. In agreement with this view, a model proposed by Kassab and Alexandre () predicts that neuro‐modulatory signals may act in concert with cortical inputs to inform the DG about the changing demands on pattern separation under different conditions. According to this model, the hilus of the DG may serve as a convergent zone whereby bottom‐up factors (i.e., pattern similarity) interact with top‐down factors (i.e., motivation), which jointly determine the engagement of pattern separation.…”

“…However, children’s abilities to spontaneously form memories with high resolution may not reflect what they can do when motivated to encode and retrieve the specific details of the studied objects. In fact, signals from extra‐hippocampal structures that carry information about behavioral significance—emotional, motivational, or attentional signals—can influence pattern separation (reviewed in Kassab & Alexandre, ). Several studies have demonstrated that arousal evoked at encoding may enhance subsequent mnemonic discrimination in young adults (Balderston et al, ; Segal, Stark, Kattan, Stark, & Yassa, ).…”

Gain-loss framing enhances mnemonic discrimination in preschoolers

“…The author suggested that this facilitation in pattern separation for items encoded during threat might be mediated by noradrenergic activity during encoding. In agreement with this view, a model proposed by Kassab and Alexandre (2018) predicts that neuro-modulatory signals may act in concert with cortical inputs to inform the DG about the changing demands on pattern separation under different conditions. According to this model, the hilus of the DG may serve as a convergent zone whereby bottom-up factors (i.e., pattern similarity) interact with top-down factors (i.e., motivation), which jointly determine the engagement of pattern separation.…”

“…However, children's abilities to spontaneously form memories with high resolution may not reflect what they can do when motivated to encode and retrieve the specific details of the studied objects. In fact, signals from extra-hippocampal structures that carry information about behavioral significance-emotional, motivational, or attentional signals-can influence pattern separation (reviewed in Kassab & Alexandre, 2018). Several studies have demonstrated that arousal evoked at encoding may enhance subsequent mnemonic discrimination in young adults (Balderston et al, 2017;Segal, Stark, Kattan, Stark, & Yassa, 2012).…”

Gaze Fixation Patterns Correlate with Visual Attention and Memory: the Results of a Pilot Study in Healthy Subjects

“…In the recent decade, quite a few studies were devoted to these mechanisms in animals and humans [2][3][4][5][6][7]. In these research projects, the authors mainly described the mapping and localization of the pattern separation function throughout the hippocampus, the structure involved in the formation and extraction of new memories.…”