Changes in hippocampal interneuronal activity during acquisition and consolidation of trace eyeblink conditioning in mice

Abstract

Objective To investigate the changes and features of firing activities of interneurons in dorsal hippocampus during the acquisition and consolidation of associative memory. Methods Trace eyeblink conditioning (tEBC) was utilized as a behavioral model of associative memory.A total of 18 wild-type C57BL/6 mice (male, 10~12 weeks old, weighing 22~25 g) were randomly divided into a paired group (n=9) and an unpaired group (n=9).Paired presentations of conditioned stimulus (CS) and unconditioned stimulus (US) were utilized to train these mice.The mice from the paired group were given US training in 250 ms after CS training, and those from the unpaired group received similar doses of CS and US training, but with no paired relationship in time.After 4 consecutive days'training, the mice of the paired group acquired tEBC, manifesting conditioned eyeblink responses (CR).Tetrode arrays were applied to record neuronal activity in dorsal hippocampus during both tEBC training epoch and the 1.5 h epoch after training.The putative interneurons (n=105) were identified according to their firing rate and spike width from trough to peak.Specific changes in hippocampal interneurons activity during tEBC training and post-training slow wave sleep were analyzed respectively. Results ① At the early stage of CR acquisition (the 1st and 2nd days), CS could evoke significantly greater activity of dorsal hippocampal interneurons in the paired group (P < 0.05).During sharp wave ripples (SWR) in the post-training slow wave sleep, the firing rate of dorsal hippocampal interneurons was significantly lower in the paired group than the unpaired group (P < 0.05).②At the late stage of CR acquisition (the 3rd and 4th days), no significant differences in CS evoked activity of dorsal hippocampal interneurons were observed between the paired group and unpaired group, neither in the firing rate of dorsal hippocampal interneurons during SWR in the post-training slow wave sleep between the 2 groups. Conclusion The dorsal hippocampal interneurons show opposite changes in firing activity during the acquisition and consolidation of associative memory.

Keywords

• hippocampus
• interneuron
• eyeblink conditioning
• slow wave sleep
• sharp wave ripple