Behavioural investigation of the effects of different forms of long term depression on the erasure of learned hippocampal spatial information

Learning occurs through activity-dependent synaptic potentiation mechanisms, which form the neural basis for lasting behavioral changes, particularly long-term potentiation. In contrast, while it is known that long-term depression plays a decisive role in the processes of erasure, modulation, or gradual loss of acquired knowledge, the molecular and circuit-level processes underlying these mechanisms have not yet been fully understood. Although there is a substantial body of literature on memory encoding, how consolidated information is erased through various forms of long term depression and the relationship of these processes to behavioral outcomes remain an open question of ongoing importance in neuroscience research.

The primary objective of this study is to conduct a comparative behavioral analysis of the effects of different forms of long term depression—chemically induced by low-frequency stimulation (LFS) and the Group I metabotropic glutamate receptor agonist 3,5-dihidroksifenilglisin (DHPG)—on the erasure of spatial information learned at the hippocampal level and transferred to long-term memory.

Two-month-old male wistar albino rats were used in the study. The rats were divided into three main groups: Sham, low frequency stimulation, and DHPG. An 8-arm Radial Arm Maze was used to measure spatial learning and memory performance. After a 3-day habituation period, the rats were trained for 8 days to enter the food-rewarded arms. Following training, group-specific LFS or DHPG protocols will be applied via stereotaxic surgical methods to erase the consolidated information. Following a one-week recovery period after the surgical intervention, the rats will be retested in the radial arm maze; changes in memory performance will be analyzed based on reference memory errors, and maze complete times.

In the evaluation of the learning process, it was observed that maze completion times significantly decreased over the days in all groups (p<0.001). This finding indicates that all three groups demonstrated spatial learning in the radial arm maze over time. Groupday interraction was surprisingly significant. This was an unanticipated findings. It is thought that this is due to differences in the motor activation of the rats in the groups. When reference memory error counts were examined, a significant decrease was observed over the days (p<0.001). The groupday effect (p=0.658) was not significant. This indicates that the groups exhibited similar learning behaviors during the 8-day learning process. On the test day, no significant difference was found between the groups in terms of maze completion times. In contrast, reference memory error counts showed a distinct difference between groups (p<0.001); the Sham group made significantly fewer errors compared to both the LFS (p<0.001) DHPG (p<0.001) groups. There was no significant difference between the LFS and DHPG groups (p=0.511). These results indicate that both treatments impaired spatial reference memory to a similar extent. Given that DHPG acts via the induction of chemical long term depression, the findings support the hypothesis that synaptic depression mechanisms may play a functional role in memory consolidation or retrieval.

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