Publishing type：Research paper (scientific journal)   Kind of work：Single Work  

Publishing type：Research paper (scientific journal)   Kind of work：Joint Work   International / domestic magazine：International journal  

New memories are believed to be consolidated over several hours of post-task sleep. The reactivation or “replay” of hippocampal cell assemblies has been proposed to provide a key mechanism for this process. However, previous studies have indicated that such replay is restricted to the first 10–30 min of post-task sleep, suggesting that it has a limited role in memory consolidation. We performed long-duration recordings in sleeping and behaving male rats and applied methods for evaluating the reactivation of neurons in pairs as well as in larger ensembles while controlling for the continued activation of ensembles already present during pre-task sleep (“preplay”). We found that cell assemblies reactivate for up to 10 h, with a half-maximum timescale of ∼6 h, in sleep following novel experience, even when corrected for preplay. We further confirmed similarly prolonged reactivation in post-task sleep of rats in other datasets that used behavior in novel environments. In contrast, we saw limited reactivation in sleep following behavior in familiar environments. Overall, our findings reconcile the duration of replay with the timescale attributed to cellular memory consolidation and provide strong support for an integral role of replay in memory.

DOI： 10.1523/JNEUROSCI.1950-18.2018

PubMed

Authorship：Lead author   Publishing type：Research paper (scientific journal)   Kind of work：Joint Work   International / domestic magazine：International journal  

Neurons fire at highly variable intrinsic rates and recent evidence suggests that low- and high-firing rate neurons display different plasticity and dynamics. Furthermore, recent publications imply possibly differing rate-dependent effects in hippocampus versus neocortex, but those analyses were carried out separately and with potentially important differences. To more effectively synthesize these questions, we analyzed the firing rate dynamics of populations of neurons in both hippocampal CA1 and frontal cortex under one framework that avoids the pitfalls of previous analyses and accounts for regression to the mean (RTM). We observed several consistent effects across these regions. While rapid eye movement (REM) sleep was marked by decreased hippocampal firing and increased neocortical firing, in both regions firing rate distributions widened during REM due to differential changes in high- versus low-firing rate cells in parallel with increased interneuron activity. In contrast, upon non-REM (NREM) sleep, firing rate distributions narrowed while interneuron firing decreased. Interestingly, hippocampal interneuron activity closely followed the patterns observed in neocortical principal cells rather than the hippocampal principal cells, suggestive of long-range interactions. Following these undulations in variance, the net effect of sleep was a decrease in firing rates. These decreases were greater in lower-firing hippocampal neurons but also higher-firing frontal cortical neurons, suggestive of greater plasticity in these cell groups. Our results across two different regions, and with statistical corrections, indicate that the hippocampus and neocortex show a mixture of differences and similarities as they cycle between sleep states with a unifying characteristic of homogenization of firing during NREM and diversification during REM.

DOI： 10.1038/s41598-018-36710-8

PubMed

Publishing type：Research paper (scientific journal)   Kind of work：Joint Work   International / domestic magazine：International journal  

Authorship：Lead author   Publishing type：Research paper (scientific journal)   Kind of work：Joint Work   International / domestic magazine：International journal  

DOI： 10.1093/sleep/zsx066

PubMed

Publishing type：Research paper (scientific journal)   Kind of work：Joint Work   International / domestic magazine：International journal  

DOI： 10.1016/j.neures.2017.04.018

PubMed

Authorship：Lead author   Publishing type：Research paper (scientific journal)   Kind of work：Joint Work   International / domestic magazine：International journal  

DOI： 10.1016/j.cub.2016.02.024

PubMed

J-GLOBAL

Publishing type：Research paper (scientific journal)   Kind of work：Joint Work   International / domestic magazine：International journal  

DOI： 10.1523/JNEUROSCI.0144-13.2013

PubMed

J-GLOBAL

Authorship：Lead author   Publishing type：Research paper (scientific journal)   Kind of work：Joint Work   International / domestic magazine：International journal  

DOI： 10.1002/syn.20860

PubMed

J-GLOBAL

Publishing type：Research paper (scientific journal)   Kind of work：Joint Work   International / domestic magazine：International journal  

Purkinje cells are the sole output neurons of the cerebellar cortex and their dysfunction causes severe ataxia. We found that Purkinje cells could be robustly generated from mouse embryonic stem (ES) cells by recapitulating the self-inductive signaling microenvironments of the isthmic organizer. The cell-surface marker Neph3 enabled us to carry out timed prospective selection of Purkinje cell progenitors, which generated morphologically characteristic neurons with highly arborized dendrites that expressed mature Purkinje cell-specific markers such as the glutamate receptor subunit GluRδ2. Similar to mature Purkinje cells, these neurons also showed characteristic spontaneous and repeated action potentials and their postsynaptic excitatory potentials were generated exclusively through nonNMDA glutamate receptors. Fetal transplantation of precursors isolated by fluorescence-activated cell sorting showed orthotopic integration of the grafted neurons into the Purkinje cell layer with their axons extending to the deep cerebellar nuclei and dendrites receiving climbing and parallel fibers. This selective preparation of bona fide Purkinje cells should aid future investigation of this important neuron.

DOI： 10.1038/nn.2638

PubMed

J-GLOBAL

Publishing type：Article, review, commentary, editorial, etc. (scientific journal)  

DOI： 10.1016/j.neures.2009.09.112

Publishing type：Article, review, commentary, editorial, etc. (scientific journal)  

Presentation type：Oral presentation (general)  

Presentation type：Oral presentation (invited, special)  

Venue：Ribeirão Preto, Brazil  

Sleep positively impacts various types of memories, including those that are hippocampal dependent. However, it is still not clear how hippocampal activity changes during sleep. To investigate this, we performed in vivo large-scale electrophysiological recordings on hippocampal CA1 region of rats in natural awake/sleep cycles. We recorded neuronal activity continuously up to 72 hours in 12-hour light and 12-hour dark cycles.
In rodents, sleep consists of two distinct states. One is REM (rapid eye movement) that is characterized by an increase in power in the theta band (5-10 Hz). The other is non-REM that is characterized by transient oscillatory events - sleep spindles and sharp wave ripples (SWRs) and continuous slow (0.5 - 4Hz) oscillation. We found that non-REM firing rates decreased during long-lasting sleep, in contrast to extended wake states where firing rates increased gradually in the hippocampus. In addition, incidences of sleep spindles and SWRs and slow-wave amplitudes decreased across sleep. These changes were not correlated with circadian cycles. These results demonstrate that hippocampal activities depend on sleep/awake history.
In the triplets of non-REM1/REM/non-REM2, mean firing rates in non-REM2 were significantly lower than in non-REM1. Firing rates in non-REM1 tightly coupled with changes in firing rates between non-REM1 and non-REM2. In addition, incidence of sleep spindles and SWRs were also strongly correlated with firing rates and the firing rates changes. As previously reported by Grosmark et al. (2012), we observed significant correlation between firing rate changes between non-REM epochs and power in theta during interleaved REM. However, this correlation was weaker than incidence of spindles, SWRs, or firing rates in non-REM. In addition, we found firing rates in non-REM were predictive of theta power in the following REM. These results indicate more “excitable” states induce larger decrease of firing in the hippocampus.
We also investigated correlation between hippocampal firing and slow wave oscillation. In the neocortex, it is argued that slow-wave oscillations have a role to decrease neuronal firing through downscaling synaptic connectivity (Tononi & Cirelli, 2014). However, we did not find significant correlations between slow-wave oscillations in the hippocampus and firing rates or changes in firing rates, which may indicate the hippocampus operate under a different set of rules from the neocortex.
We found that hippocampal activity gradually decreased across sleep, and enhanced excitability in the hippocampus induced large decrease of hippocampal firing, which may contribute to maintain homeostasis in the hippocampus.