Impairment of Pattern Separation of Ambiguous Scenes by Single Units in the CA3 in the Absence of the Dentate Gyrus

Abstract

Theoretical models and experimental evidence have suggested that connections from the dentate gyrus (DG) to CA3 play important roles in representing orthogonal information (i.e., pattern separation) in the hippocampus. However, the effects of eliminating the DG on neural firing patterns in the CA3 have rarely been tested in a goal-directed memory task that requires both the DG and CA3. In this study, selective lesions in the DG were made using colchicine in male Long-Evans rats, and single units from the CA3 were recorded as the rats performed visual scene memory tasks. The original scenes used in training were altered during testing by blurring to varying degrees or by using visual masks, resulting in maximal recruitment of the DG-CA3 circuits. Compared with controls, the performance of rats with DG lesions was particularly impaired when blurred scenes were used in the task. In addition, the firing rate modulation associated with visual scenes in these rats was significantly reduced in the single units recorded from the CA3 when ambiguous scenes were presented, largely because DGdeprived CA3 cells did not show stepwise, categorical rate changes across varying degrees of scene ambiguity compared with controls. These findings suggest that the DG plays key roles not only during the acquisition of scene memories but also during retrieval when modified visual scenes are processed in conjunction with the CA3 by making the CA3 network respond orthogonally to ambiguous scenes.

Differential encoding of place value between the dorsal and intermediate hippocampus

“…85,86 The robust rate remapping that commonly occurred in one-third of place cells recorded from both dHP and iHP across different reward conditions in our study suggests that rate remapping might not be used as a neural code for signaling changes in motivational significance in the hippocampus. It is also clear from the literature that most rate-remapping experiments manipulated environmental factors, such as the shape of the recording arena and sensory stimuli, 13,83,85,[87][88][89] instead of a motivational value.…”

Deficits in Behavioral and Neuronal Pattern Separation in Temporal Lobe Epilepsy

“…Because bursts are known to be more efficient at driving spiking in CA3 pyramidal neurons (Henze et al, 2002), a single GC firing bursts will have a higher probability of making downstream CA3 pyramidal cells fire. This could have deleterious effects on memory encoding and promote seizures, as more active CA3 neurons would 1) increase the chance of overlap between memory representations (Madar et al, 2019a, 2019b; Lee and Lee, 2020) and 2) overexcite a recurrent excitatory circuit, a mechanism of seizure generation (Traub and Wong, 1982; Santhakumar et al, 2005; de la Prida et al, 2006). Thus, our findings are consistent with the idea that pathological firing or bursting of even a subset of GCs could simultaneously contribute to deficits in mnemonic discrimination and epileptiform activity in TLE.…”

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

“…Given the prominent efferent connections from the FC to the DG identified in our study, we tested the functional roles of the FC in a visual contextual memory (VCM) task, which requires intact DG function in rats Lee, 2020). For this purpose, we developed an FC-lesion model using colchicine, which is known to fairly selectively eliminate the DG, leaving other subregions largely unaffected (Walsh et al, 1986).…”

“…How could the FC contribute to hippocampal learning and memory? Considering that the FC sends its major output only to the DG in the hippocampus, we recorded single units from the FC while the rat performed the VCM task Lee, 2020)-the same task previously used for examining the effects of FC lesions (Fig. 3).…”

“…3). We have demonstrated that, in the VCM task, the DG is necessary for CA3 cells to exhibit pattern-separating signals between different visual contextual environments (Lee and Lee, 2020). In the modified version of the task, rats were trained with familiar visual contexts before receiving hyperdrive-implanting surgery.…”