Search

Sleep facilitates memory storage and even brief periods of sleep loss lead to impairments in memory, particularly memories that are hippocampus dependent. In previous studies, we have shown that the deficit in memory seen after sleep loss is accompanied by deficits in synaptic plasticity. Our previous work has also found that sleep deprivation (SD) is associated with reduced levels of cyclic adenosine monophosphate (cAMP) in the hippocampus and that the reduction of cAMP mediates the diminished memory observed in sleep-deprived animals. Based on these findings, we hypothesized that cAMP acts as a mediator for not only the cognitive deficits caused by sleep deprivation, but also the observed deficits in synaptic plasticity. In this study, we expressed the heterologous Drosophila melanogaster Gαs-protein-coupled octopamine receptor (DmOctβ1R) in mouse hippocampal neurons. This receptor is selectively activated by the systemically injected ligand (octopamine), thus allowing us to increase cAMP levels in hippocampal neurons during a 5-h sleep deprivation period. Our results show that chemogenetic enhancement of cAMP during the period of sleep deprivation prevents deficits in a persistent form of long-term potentiation (LTP) that is induced at the Schaffer collateral synapses in the hippocampal CA1 region. We also found that elevating cAMP levels in either the first or second half of sleep deprivation successfully prevented LTP deficits. These findings reveal that cAMP-dependent signaling pathways are key mediators of sleep deprivation at the synaptic level. Targeting these pathways could be useful in designing strategies to prevent the impact of sleep loss., Competing Interests: The authors declare no competing financial interests., (Copyright © 2023 Walsh et al.)

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. SIGNIFICANCE STATEMENT Neurons that are active during an experience reactivate again afterward during rest and sleep. This replay of ensembles of neurons has been proposed to help strengthen memories, but it has also been reported that replay occurs only in the first 10-30 min of sleep, suggesting a circumscribed role. We performed long-duration recordings in the hippocampus of rats and found that replay persists for several hours in sleep following novel experience, far beyond the limits found in previous reports based on shorter recordings. These findings reconcile the duration of replay with the hours-long timescales attributed to memory consolidation., (Copyright © 2019 the authors 0270-6474/19/390866-10$15.00/0.)

The perirhinal cortex (PER), which is critical for associative memory and stimulus discrimination, has been described as a wall of inhibition between the neocortex and hippocampus. With advanced age, rats show deficits on PER-dependent behavioral tasks and fewer PER principal neurons are activated by stimuli, but the role of PER interneurons in these altered circuit properties in old age has not been characterized. In the present study, PER neurons were recorded while rats traversed a circular track bidirectionally in which the track was either empty or contained eight novel objects evenly spaced around the track. Putative interneurons were discriminated from principal cells based on the autocorrelogram, waveform parameters, and firing rate. While object modulation of interneuron firing was observed in both young and aged rats, PER interneurons recorded from old animals had lower firing rates compared with those from young animals. This difference could not be accounted for by differences in running speed, as the firing rates of PER interneurons did not show significant velocity modulation. Finally, in the aged rats, relative to young rats, there was a significant reduction in detected excitatory and inhibitory monosynaptic connections. Together these data suggest that with advanced age there may be reduced afferent drive from excitatory cells onto interneurons that may compromise the wall of inhibition between the hippocampus and cortex. This circuit dysfunction could erode the function of temporal lobe networks and ultimately contribute to cognitive aging. SIGNIFICANCE STATEMENT We report that lower firing rates observed in aged perirhinal cortical principal cells are associated with weaker interneuron activity and reduced monosynaptic coupling between excitatory and inhibitory cells. This is likely to affect feedforward inhibition from the perirhinal to the entorhinal cortex that gates the flow of information to the hippocampus. This is significant because cognitive dysfunction in normative and pathological aging has been linked to hyperexcitability in the aged CA3 subregion of the hippocampus in rats, monkeys, and humans. The reduced inhibition in the perirhinal cortex reported here could contribute to this circuit imbalance, and may be a key point to consider for therapeutic interventions aimed at restoring network function to optimize cognition., (Copyright © 2017 the authors 0270-6474/17/378965-10$15.00/0.)

During the crossing of the place field of a pyramidal cell in the rat hippocampus, the firing phase of the cell decreases with respect to the local theta rhythm. This phase precession is usually studied on the basis of data in which many place field traversals are pooled together. Here we study properties of phase precession in single trials. We found that single-trial and pooled-trial phase precession were different with respect to phase-position correlation, phase-time correlation, and phase range. Whereas pooled-trial phase precession may span 360 degrees , the most frequent single-trial phase range was only approximately 180 degrees. In pooled trials, the correlation between phase and position (r = -0.58) was stronger than the correlation between phase and time (r = -0.27), whereas in single trials these correlations (r = -0.61 for both) were not significantly different. Next, we demonstrated that phase precession exhibited a large trial-to-trial variability. Overall, only a small fraction of the trial-to-trial variability in measures of phase precession (e.g., slope or offset) could be explained by other single-trial properties (such as running speed or firing rate), whereas the larger part of the variability remains to be explained. Finally, we found that surrogate single trials, created by randomly drawing spikes from the pooled data, are not equivalent to experimental single trials: pooling over trials therefore changes basic measures of phase precession. These findings indicate that single trials may be better suited for encoding temporally structured events than is suggested by the pooled data.