Adult neurogenesis mediates forgetting of multiple types of memory in the rat

The formation and retention of hippocampus-dependent memories is impacted by neurogenesis, a process that involves the production of new neurons in the dentate gyrus of the hippocampus. Recent studies demonstrate that increasing neurogenesis after memory formation induces forgetting of previously acquired memories. Neurogenesis-induced forgetting was originally demonstrated in mice, but a recent report suggests that the same effect may be absent in rats. Although a general species difference is possible, other potential explanations for these incongruent findings are that memories which are more strongly reinforced become resilient to forgetting or that perhaps only certain types of memories are affected. Here, we investigated whether neurogenesis-induced forgetting occurs in rats using several hippocampal dependent tasks including contextual fear conditioning (CFC), the Morris Water Task (MWT), and touchscreen paired associates learning (PAL). Neurogenesis was increased following training using voluntary exercise for 4 weeks before recall of the previous memory was assessed. We show that voluntary running causes forgetting of context fear memories in a neurogenesis-dependent manner, and that neurogenesis-induced forgetting is present in rats across behavioral tasks despite differences in complexity or reliance on spatial, context, or object memories. In addition, we asked whether stronger memories are less susceptible to forgetting by varying the strength of training. Even with a very strong training protocol in the CFC task, we still observed enhanced forgetting related to increased neurogenesis. These results suggest that forgetting due to neurogenesis is a conserved mechanism that aids in the clearance of memories.Significance StatementRecent evidence indicates that hippocampal neurogenesis mediates forgetting of older memories and enhances encoding of new memories free of proactive interference. This evidence comes from multiple rodent species, behavioral tasks, and methods of increasing neurogenesis. However, a recent paper by (Kodali et al. 2016) found that voluntary exercise-induced neurogenesis did not cause forgetting in the Morris Water Task in rats. The results call into question whether the phenomenon is a conserved function of neurogenesis across species. In the present study, we show that voluntary running causes robust forgetting in rats in a neurogenesis-dependent manner and that the effect is present across three different behavioral tasks, confirming the existence of the phenomenon in rats and adding to the growing evidence that forgetting is a conserved function of hippocampal neurogenesis.

Generalisation decrement and not overshadowing by associative competition among pairs of landmarks in a navigation task with humans

In three experiments, a virtual preparation for humans of the Morris water task (VMWT) was used. Experiment 1 established that four landmarks were of similar salience. Then, in Experiments 2 and 3, participants were trained to locate a hidden platform in the presence or either two or four of the previous landmarks. In Experiment 2, one pair of groups was trained with four visual landmarks spaced at equal intervals around the edge of the pool, while a second pair was trained with two landmarks only, either relatively close to or far from the hidden platform. After training, a reciprocal overshadowing effect was found: on a test without the platform with two landmarks only (either close to or far from the platform position), the participants trained with four landmarks spent less time in the platform quadrant than those trained with only two. Finally, Experiment 3 showed that at least participants trained with two landmarks relatively close to the platform and then tested with four also performed worse on test than those trained and tested with two close landmarks only. This result suggests that generalisation decrement, rather than associative competition, could provide a sufficient explanation for the overshadowing observed in Experiment 2 in the proximal groups. The present set of experiments extend, although only partially, the generalisation decrement results documented in rats to human participants.

Progressive impairment of directional and spatially precise trajectories by TgF344-AD Rats in the Morris Water Task

Spatial navigation is impaired in early stages of Alzheimer’s disease (AD), and may be a defining behavioral marker of preclinical AD. Nevertheless, limitations of diagnostic criteria for AD and within animal models of AD make characterization of preclinical AD difficult. A new rat model (TgF344-AD) of AD overcomes many of these limitations, though spatial navigation has not been comprehensively assessed. Using the hidden and cued platform variants of the Morris water task, a longitudinal assessment of spatial navigation was conducted on TgF344-AD (n=16) and Fischer 344 (n=12) male and female rats at three age ranges: 4 to 5 months, 7 to 8, and 10 to 11 months of age. TgF344-AD rats exhibited largely intact navigation at 4-5 and 7-8 months of age, with deficits in the hidden platform task emerging at 10-11 months of age. In general, TgF344-AD rats displayed less accurate swim trajectories to the platform and a wider search area around the platform region compared to wildtype rats. Impaired navigation occurred in the absence of deficits in acquiring the procedural task demands or navigation to the cued platform location. Together, the results indicate that TgF344-AD rats exhibit comparable deficits to those found in individuals in the early stages of AD.

A variant of the Morris water task for assessing learning and memory processes in mice

The Morris water task (MWT) is commonly used to assess rodent spatial learning and memory. Our goal was to develop a 3-phase variant of the hidden goal water task to assess old and new spatial memories acquired in the same context using various measures of spatial learning in C57BL/6 mice. In the first phase, mice were pre-trained to an initially hidden location. The second phase consisted of a massed training session to a new location in the same apparatus and context. The final phase consisted of a competition test between the original and new platform locations. AppNL-G-F/NL-G-F mice, a novel transgenic mouse model for Alzheimer’s disease (AD), were also used as an independent variable to validate this 3-phase variant of MWT. The results of the present study showed that C57 mice acquired and retained both the old and new location representations; however, AppNL-G-F/NL-G-F mice retained a recently acquired spatial memory but did not remember the old location acquired in the same apparatus and context. The results showed that C57 mice can show precise place learning and memory with the right amount of training and acquire and retain multiple spatial memory locations in the same environment whereas this ability was impaired in AppNL-G-F/NL-G-F mice. In the visible platform test, however, all groups of mice showed normal sensorimotor ability and motivation. These findings indicate that this new version of the MWT provides a robust way for assessment of old and new memories in mice. This paradigm could also be exploited to assess manipulations of neural circuits implicated in learning and memory processes as well as for research investigating human brain diseases.