Hippocampal Network Oscillations Rescue Memory Consolidation Deficits Caused by Sleep Loss

Abstract

Oscillations in the hippocampal network during sleep are proposed to play a role in memory storage by patterning neuronal ensemble activity. Here we show that following single-trial fear learning, sleep deprivation (which impairs memory consolidation) disrupts coherent firing rhythms in hippocampal area CA1. State-targeted optogenetic inhibition of CA1 parvalbumin-expressing (PV+) interneurons during postlearning NREM sleep, but not REM sleep or wake, disrupts contextual fear memory (CFM) consolidation in a manner similar to sleep deprivation. NREM-targeted inhibition disrupts CA1 network oscillations which predict successful memory storage. Rhythmic optogenetic activation of PV+ interneurons following learning generates CA1 oscillations with coherent principal neuron firing. This patterning of CA1 activity rescues CFM consolidation in sleep-deprived mice. Critically, behavioral and optogenetic manipulations that disrupt CFM also disrupt learning-induced stabilization of CA1 ensembles’ communication patterns in the hours following learning. Conversely, manipulations that promote CFM also promote long-term stability of CA1 communication patterns. We conclude that sleep promotes memory consolidation by generating coherent rhythms of CA1 network activity, which provide consistent communication patterns within neuronal ensembles. Most importantly, we show that this rhythmic patterning of activity is sufficient to promote long-term memory storage in the absence of sleep.

Optogenetic intervention of seizures improves spatial memory in a mouse model of chronic temporal lobe epilepsy

“…Our findings are further supported by studies that found that targeting and activation of parvalbumin interneurons at specific stimulation frequencies could ameliorate spatial learning deficits. For example, rhythmic PV interneuron activation in the hippocampal CA1 in sleep‐deprived animals during non‐REM sleep improved performance in memory tasks . Because seizures in IHKA mice can occur during all brain states, with a majority (~90%) arising from a non‐theta state, animals in our present study likely received some light activation of PV interneurons during non‐REM sleep at a theta frequency (~7 Hz) similar to that used in the described study .…”

“…For example, rhythmic PV interneuron activation in the hippocampal CA1 in sleep-deprived animals during non-REM sleep improved performance in memory tasks. 33 Because seizures in IHKA mice can occur during all brain states, with a majority (~90%) arising from a non-theta state, 34 animals in our present study likely received some light activation of PV interneurons during non-REM sleep at a theta frequency (~7 Hz) similar to that used in the described study. 33 Rhythmic activation of PV interneurons has been shown to have therapeutic effects in the gamma frequency as well.…”

“…33 Because seizures in IHKA mice can occur during all brain states, with a majority (~90%) arising from a non-theta state, 34 animals in our present study likely received some light activation of PV interneurons during non-REM sleep at a theta frequency (~7 Hz) similar to that used in the described study. 33 Rhythmic activation of PV interneurons has been shown to have therapeutic effects in the gamma frequency as well. This stimulation paradigm has been shown to reduce the pathology in a model of Alzheimer disease, by activating glial responses.…”

“…16 Fourth, it is unknown if targeting seizures is required for the beneficial effects in learning and memory or if random or periodic PV activation could also work, especially considering experimental results indicating that PV interneuron activation itself can improve different pathologies. 33,36 Fifth, the long-term effects of closed-loop intervention and optogenetic stimulation will need to be determined, that is, whether the beneficial effects of the closedloop seizure suppression end immediately after the end of the treatment, or if there are any lasting effects on seizures or cognitive ability. Sixth, it should be noted that it is not yet entirely clear whether unilateral optogenetic intervention in this paradigm achieves curtailment of seizures primarily by exciting the somata, dendrites, or axon terminals of those ipsilateral PV cells that survived the kainate administration ( Figure S1), despite being greatly reduced in number, 37,38 and/or by activating the ipsilateral axon terminals of contralaterally located PV cells that have been shown recently to undergo a prominent sprouting response after IHKA treatment.…”

“…For example, seizure suppression was achieved not only by PV interneuron activation, but also by inhibition of principal neurons in the dorsal hippocampus . Fourth, it is unknown if targeting seizures is required for the beneficial effects in learning and memory or if random or periodic PV activation could also work, especially considering experimental results indicating that PV interneuron activation itself can improve different pathologies . Fifth, the long‐term effects of closed‐loop intervention and optogenetic stimulation will need to be determined, that is, whether the beneficial effects of the closed‐loop seizure suppression end immediately after the end of the treatment, or if there are any lasting effects on seizures or cognitive ability.…”