P103 Developmental Changes in Circuit Dynamics during Hippocampal Memory Recall
Inês Guerreiro*1, Laurenz Muessig2, Thomas Wills2,Francesca Cacucci1
1Neuroscience, Physiology and Pharmacology, University College London, London, UK 2Cell and Developmental Biology, University College London, London, UK
*Email: ines.completo@gmail.com
Introduction
Replay of spike sequences during sharp wave ripples (SPW-Rs) in the hippocampus during sleep is believed to aid memory transfer from the hippocampus to the neocortex. The generation of SPW-Rs has been widely studied, but most studies focus on adult rats. Since hippocampal memory develops late in development [1,2,3], understanding the developmental changes in circuit dynamics during recall is key to uncovering how memory processing mechanisms mature over time.
Previous studies show that coordinated sequence replay emerges during development and that plasticity between co-firing cells has a higher threshold in pups than in adults [4]. Here, we investigate the mechanistic differences in replay in pups and adults. Methods We examined the development of hippocampal activity using LFP and single neuron recordings from the hippocampal CA1 area during post-run sleep in rats. Rats with ages ranging from postnatal days (P)17 to 6 months old were used in our analysis. We first analysed differences in mean firing rates between interneurons and pyramidal cells during sleep in both pups and adults to assess developmental changes in activity patterns during replay.Next, we examined the firing patterns of identified interneurons during sharp wave ripples. By doing so, we can classify the interneuron subtypes recorded and examine their potential contributions to replay events. Results Preliminary results show that during post-run sleep, excitatory and inhibitory neurons in pups have higher firing rates than in adults.This contrasts with run trials, where the frequency of inhibitory neurons is lower in pups. Significant variability in interneuron spiking activity was also observed during both run and sleep, emphasizing the diversity of inhibitory interneurons in the CA1 region. Once the subclasses of interneurons and their behaviour duringSPW-Rsare identified, one can develop a canonical model to examine how the CA1 circuit in pups and adults modulates sequence replay during SWRs.
Discussion Different types of interneurons participate in SPW-Rs and are recruited differently during replay events [5, 6].Given their essential role in SWR generation, replay, and memory processing, understanding how inhibitory neuron activity differs between pups and adults during run and sleep trials is crucial. These developmental differences in interneuron dynamics may influence memory consolidation processes. This work aims to reveal how the CA1 microcircuit regulates the replay of temporally ordered memory patterns throughout development and to clarify the distinct roles of various inhibitory interneuron types in this process.
Acknowledgements We acknowledge funding from theWellcome Trust Senior Research Fellowship 220886/Z/20/Z (T.W), and the European Research Council Consolidator Award DEVMEM (FC). References 1. doi: 10.1038/nn0717-1033a. PMID: 27428652; PMCID: PMC5003643. 2. doi: 10.1126/science.1188224. PMID: 20558720; PMCID: PMC3543985. 3. doi: 10.1126/science.1188210. PMID: 20558721 4. doi: 10.1016/j.cub.2019.01.005 5. doi: 10.1523/JNEUROSCI.19-01-00274.1999 6. doi: 10.1523/JNEUROSCI.3962-09.2010. PMID: 20427657; PMCID: PMC3763476
