Intact CA3 in the hippocampus is only sufficient for contextual behavior based on well‐learned and unaltered visual background

Abstract

Computational models suggest that the dentate gyrus and CA3 subfields of the hippocampus are responsible for discrete memory representations using pattern separation and pattern completion when a modified external stimulus is recognized as an old memory or encoded as a new memory. Experimental evidence of such computational processes in the hippocampus has been obtained mostly from spatial navigational tasks, and little is known about the proposed computational functions of the hippocampal subfields in "nonspatial" memory tasks. We tested whether rats with major damage in the dentate gyrus induced by colchicine lesions could remember patterned visual scene stimuli presented on LCD screens in the background. Rats responded using a touchscreen to indicate the identity of the visual scene. Performance of the lesion group was normal when tested with familiar visual scenes that had been learned prior to surgery. Lesioned rats exhibited severe deficits in learning novel visual scenes, but eventually reached the same level of performance as controls. However, unlike in controls, novel scene-associated memories formed in the lesion group were unstable and easily disrupted when ambiguous versions of the novel scenes were presented intermixed with the original stimuli. Our findings confirm that the prior computational models can also be applied to the nonspatial memory domain and suggest that the dentate gyrus is not necessary for the retrieval of learned visual scene-associated behavioral responses but plays a crucial role in forming novel visual scene-dependent memory and recognizing altered or ambiguous visual scenes in the background.

The Human Dentate Gyrus Plays a Necessary Role in Discriminating New Memories

“…This is not unusual, as human studies of pattern separation/pattern completion typically use visual object information (e.g., Bakker et al, 2008;Kirwan et al, 2012;Tompary et al, 2016); animal studies also tend to use visual or visuospatial information (e.g., Ahn & Lee, 2014;Leutgeb et al, 2007). However, it does pose the question of whether the mnemonic phenomena being studied are specific to the visual domain.…”

“…Lesion and genetic studies in rodents point to the dentate gyrus of the hippocampus as responsible for pattern separation and the CA3 subfield for pattern completion (Ahn & Lee, 2014;Gilbert, Kesner, & Lee, 2001;Kesner, Kirk, Yu, Polansky, & Musso, 2016;McHugh et al, 2007;Nakazawa et al, 2002;Neunuebel & Knierim, 2014). This classic dissociation is predicted by computational models (e.g., O'Reilly & McClelland, 1994;Rolls, 2016;Treves & Rolls, 1994), some of which provide a pattern completion/pattern association role for CA1 (Rolls, 2016;Tompary, Duncan, & Davachi, 2016), or a pattern separation-mediating role for the CA3 (Myers, & Scharfman, 2011).…”

“…One of the most daunting challenges is how to isolate the hippocampal network, or particular neural hubs thought to implement these cognitive abilities. In this regard, particular focus must be paid to three areas of the hippocampal formation and surrounding medial temporal lobe (MTL) cortices where pattern separation/pattern completion have been localized in rodent studies (e.g., Ahn & Lee, 2014;Neunuebel & Knierim, 2014): 1) the entorhinal cortex; 2) the dentate gyrus; and, 3) the CA3 subfield of the hippocampus proper.…”

“…In order to evaluate these abilities, BL and controls were tested on the Mnemonic Similarity Task (MST; Stark, Stevenson, Wu, Rutledge, & Stark, 2015), formerly known as the Behavioral Pattern Separation Task (BPS-O; Stark et al, 2013). The MST assesses recognition memory performance using a paradigm similar to that used to test patients with hippocampal lesions (Kirwan et al, 2012) and conceptually similar to a visual recognition task used with rodents (Ahn & Lee, 2014). The MST was administered as a stand-alone application on a laptop running Windows 7.…”

The fasciola cinereum subregion of the hippocampus is important for the acquisition of visual contextual memory

“…We next sought to determine the functional significance of the FC. Given the prominent efferent connections from the FC to the DG, we tested the roles of the FC in a DG-dependent task in rats 22 . Because granule cells are present in both the DG and FC 10 , we were able to selectively lesion the FC by injecting it with colchicine (0.05 μ L/site), a neurotoxin known to cause selective degenerative effects on the DG 23,24 , while leaving the adjacent CA1 area relatively unaffected (Fig.…”