scholarly journals The gap junction blocker mefloquine impairs sleep-dependent declarative memory consolidation in humans

2019 ◽  
Author(s):  
Gordon B. Feld ◽  
Hong-Viet Ngo ◽  
Ernesto Durán ◽  
Sandra Gebhardt ◽  
Lisa Kleist ◽  
...  

AbstractDuring sleep, the time-compressed replay of engrams acquired during preceding wakefulness drives memory consolidation. We demonstrate in healthy humans that direct electrical coupling between neurons via gap junctions, i.e., electrical synapses, contributes to this beneficial effect of sleep. Twenty male participants learned a declarative word-pair task and a procedural finger sequence tapping task before receiving the antimalarial mefloquine that is known to block electrical synapses. Retrieval was tested after a retention interval of approximately 20.5 hours that included nocturnal sleep. As predicted, mefloquine given before sleep impaired the retention of declarative memory. In contrast, this effect was absent in control groups, which stayed awake or received mefloquine after sleep. Irrespective of sleep or administration time, mefloquine enhanced retention performance on the procedural memory control task. We conclude that sleep-dependent processes relying on electrical neuronal coupling enable hippocampus-dependent declarative memory consolidation, presumably via time-compressed hippocampal replay of memory traces within sharp-wave/ripple complexes. The recruitment of this understudied form of neuronal information transfer may be necessary to achieve fast-paced memory reprocessing during sleep. Considering that drugs targeting neurochemical synapses have recently fallen short of substantially advancing the treatment of memory impairments in Alzheimer’s disease, schizophrenia or during normal aging, unraveling the contribution of gap junctions to sleep-dependent declarative memory formation can be expected to open new therapeutic avenues.Significance statementSleep supports the strengthening and transformation of memory content via the active replay of previously encoded engrams. Surprisingly, blocking neurochemical synaptic transmission does not impair this function of sleep. Here we demonstrate that the direct electrical coupling between neurons via electrical synapses (gap junctions) is essential for the sleep-dependent formation of declarative memory, i.e., memory for episodes and facts. These findings are in line with the assumption that electrical synapses enable time-compressed neuronal firing patterns that emerge during sleep and drive declarative memory consolidation. Electrical synapses have so far not been linked to higher-order brain functions in humans; their contribution to sleep-dependent memory processing may provide a novel target for sleep-related clinical interventions.

2018 ◽  
Author(s):  
André Holzbecher ◽  
Richard Kempter

1AbstractSharp wave-ripple (SWRs) are important for memory consolidation. Their signature in the hippocampal extracellular field potential (EFP) can be decomposed into a ≈ 100 ms long sharp wave superimposed by ≈ 200 Hz ripple oscillations. How ripple oscillations are generated is currently not well understood. A promising model for the genesis of ripple oscillations is based on recurrent interneuronal networks (INT-INT). According to this hypothesis, the INT-INT network in CA1 receives a burst of excitation from CA3 that generates the sharp wave, and recurrent inhibition leads to an ultrafast synchronization of the CA1 network causing the ripple oscillations; fast-spiking parvalbumin-positive basket cells (PV+BCs) may constitute the ripple-generating interneuronal network. PV+BCs are also coupled by gap junctions (GJs) but the function of GJs for ripple oscillations has not been quantified. Using simulations of CA1 hippocampal networks of PV+BCs, we show that GJs promote synchrony and increase the neuronal firing rate of the interneuronal ensemble, while the ripple frequency is only affected mildly. The promoting effect of GJs on ripple oscillations depends on fast GJ transmission (≲ 0.5 ms), which requires proximal gap junction coupling (≲ 100 μm from soma).


SLEEP ◽  
2020 ◽  
Vol 43 (Supplement_1) ◽  
pp. A45-A45
Author(s):  
B Baxter ◽  
K Kwok ◽  
C Talbot ◽  
L Zhu ◽  
D Mylonas ◽  
...  

Abstract Introduction Converging evidence supports the hypothesis that reduced sleep spindles and spindle-slow oscillation (SO) coordination contribute to cognitive deficits in schizophrenia. Closed-loop auditory stimulation in healthy adults increases sleep spindles and improves declarative memory consolidation. Here we investigated whether closed-loop auditory stimulation also improves sleep-dependent procedural memory consolidation as a first step towards an intervention in schizophrenia. Methods Thirteen healthy adults participated in two nap sessions (stimulation or detection only) with polysomnography in a counterbalanced order. Participants were trained on the finger tapping Motor Sequence Task (MST), which measures sleep-dependent motor procedural memory consolidation, prior to napping and were tested after awakening. We detected the negative peak of SOs during non-REM sleep and, in the stimulation condition, delivered 50ms of pink noise during the SO up-state. Results Auditory stimulation increased SOs and spindles during the SO up-state in a frontocentral cluster of electrodes 800-1200ms after stimulation compared to detection only (p<0.05). Stimulation also showed promise for improving memory consolidation (33% increase in MST overnap improvement from detection-only) but this did not reach significance in this small sample and data collection is ongoing. Conclusion Auditory stimulation evoked coordinated spindle-SO events that mediate memory consolidation, but more subjects are needed to evaluate whether it also improves memory. If it does, we will test the effects of stimulation on sleep-dependent memory deficits in patients with schizophrenia. Closed-loop auditory stimulation shows promise as a safe, scalable intervention for cognitive deficits that can be implemented at home with commercially available devices. Support R01 MH67720 (DSM & RS), NIH-NHLBI 5T32HL007901-17 (BB), K24MH099421 (DSM), and Simons Foundation (DSM).


2020 ◽  
Vol 10 (10) ◽  
pp. 696
Author(s):  
Koyuki Ikarashi ◽  
Daisuke Sato ◽  
Kaho Iguchi ◽  
Yasuhiro Baba ◽  
Koya Yamashiro

Numerous studies have noted that sex and/or menstrual phase influences cognitive performance (in particular, declarative memory), but the effects on motor learning (ML) and procedural memory/consolidation remain unclear. In order to test the hypothesis that ML differs across menstrual cycle phases, initial ML, overlearning, consolidation, and final performance were assessed in women in the follicular, preovulation and luteal phases. Primary motor cortex (M1) oscillations were assessed neuro-physiologically, and premenstrual syndrome and interoceptive awareness scores were assessed psychologically. We found not only poorer performance gain through initial ML but also lower final performance after overlearning a day and a week later in the luteal group than in the ovulation group. This behavioral difference could be explained by particular premenstrual syndrome symptoms and associated failure of normal M1 excitability in the luteal group. In contrast, the offline effects, i.e., early and late consolidation, did not differ across menstrual cycle phases. These results provide information regarding the best time in which to start learning new sensorimotor skills to achieve expected gains.


2020 ◽  
Author(s):  
Mohammad Dastgheib

Master's thesisNumerous studies have reported that, compared to an equivalent period of wakefulness,post-training sleep (overnight or daytime naps) benefits memory consolidation (Diekelmann & Born, 2010; Mednick, Nakayama, & Stickgold, 2003; Plihal & Born, 1999; Walker et al.,2003). However, most investigations have employed various forms of “active wakefulness” (e.g., sensorimotor and cognitive tasks) as a comparison condition for sleep, while few studies have examined the role of “quiet wakefulness” in memory consolidation, even though some of the EEG oscillations during quiet waking resemble those present in sleep (e.g., increased activity in the theta-alpha range) (Brokaw et al., 2016). This study aimed to examine the consolidation of declarative (word-pair associates) andnon-declarative (marble maze visuo-motor task) learning over a 60-minutes time interval (with continuous EEG monitoring) filled with either (A) napping; (B) active-waking (watchinga video); or (C) quiet-waking (self-guided meditation).The results of the current study suggested that memory consolidation may not be a sleepspecific-phenomenon. In fact, mindfulness meditation appeared to be more advantageous than a short nap for the consolidation of declarative memories. This study also found that SWSexerts significant effects on the retention of non-declarative memory. For nappers, the absence of SWS resulted in noticeable performance enhancements compared to participants who entered SWS. Thus, it is possible that SWS plays a disadvantageous role in the consolidationof procedural memory. It is thought that sleep inertia caused by SWS is partly responsible for the impairments in tasks procedural memory. The findings of current study contribute to the understanding of memory consolidation and provide insights about the role of waking states for future studies.


2020 ◽  
Vol 63 (12) ◽  
pp. 4162-4178
Author(s):  
Emily Jackson ◽  
Suze Leitão ◽  
Mary Claessen ◽  
Mark Boyes

Purpose Previous research into the working, declarative, and procedural memory systems in children with developmental language disorder (DLD) has yielded inconsistent results. The purpose of this research was to profile these memory systems in children with DLD and their typically developing peers. Method One hundred four 5- to 8-year-old children participated in the study. Fifty had DLD, and 54 were typically developing. Aspects of the working memory system (verbal short-term memory, verbal working memory, and visual–spatial short-term memory) were assessed using a nonword repetition test and subtests from the Working Memory Test Battery for Children. Verbal and visual–spatial declarative memory were measured using the Children's Memory Scale, and an audiovisual serial reaction time task was used to evaluate procedural memory. Results The children with DLD demonstrated significant impairments in verbal short-term and working memory, visual–spatial short-term memory, verbal declarative memory, and procedural memory. However, verbal declarative memory and procedural memory were no longer impaired after controlling for working memory and nonverbal IQ. Declarative memory for visual–spatial information was unimpaired. Conclusions These findings indicate that children with DLD have deficits in the working memory system. While verbal declarative memory and procedural memory also appear to be impaired, these deficits could largely be accounted for by working memory skills. The results have implications for our understanding of the cognitive processes underlying language impairment in the DLD population; however, further investigation of the relationships between the memory systems is required using tasks that measure learning over long-term intervals. Supplemental Material https://doi.org/10.23641/asha.13250180


Author(s):  
Joshua Buffington ◽  
Alexander P. Demos ◽  
Kara Morgan-Short

Abstract Evidence for the role of procedural memory in second language (L2) acquisition has emerged in our field. However, little is known about the reliability and validity of the procedural memory measures used in this research. The present study (N = 119) examined the reliability and the convergent and discriminant validity of three assessments that have previously been used to examine procedural memory learning ability in L2 acquisition, the dual-task Weather Prediction Task (DT-WPT), the Alternating Serial Reaction Time Task (ASRT), and the Tower of London (TOL). Measures of declarative memory learning ability were also collected. For reliability, the DT-WPT and TOL tasks met acceptable standards. For validity, an exploratory factor analysis did not provide evidence for convergent validity, but the ASRT and the TOL showed reasonable discriminant validity with declarative memory measures. We argue that the ASRT may provide the purest engagement of procedural memory learning ability, although more reliable dependent measures for this task should be considered. The Serial Reaction Time task also appears promising, although we recommend further consideration of this task as the present analyses were post hoc and based on a smaller sample. We discuss these results regarding the assessment of procedural memory learning ability as well as implications for implicit language aptitude.


2021 ◽  
Vol 11 (2) ◽  
pp. 261
Author(s):  
Frank J. van Schalkwijk ◽  
Walter R. Gruber ◽  
Laurie A. Miller ◽  
Eugen Trinka ◽  
Yvonne Höller

Memory complaints are frequently reported by patients with epilepsy and are associated with seizure occurrence. Yet, the direct effects of seizures on memory retention are difficult to assess given their unpredictability. Furthermore, previous investigations have predominantly assessed declarative memory. This study evaluated within-subject effects of seizure occurrence on retention and consolidation of a procedural motor sequence learning task in patients with epilepsy undergoing continuous monitoring for five consecutive days. Of the total sample of patients considered for analyses (N = 53, Mage = 32.92 ± 13.80 y, range = 18–66 y; 43% male), 15 patients experienced seizures and were used for within-patient analyses. Within-patient contrasts showed general improvements over seizure-free (day + night) and seizure-affected retention periods. Yet, exploratory within-subject contrasts for patients diagnosed with temporal lobe epilepsy (n = 10) showed that only seizure-free retention periods resulted in significant improvements, as no performance changes were observed following seizure-affected retention. These results indicate general performance improvements and offline consolidation of procedural memory during the day and night. Furthermore, these results suggest the relevance of healthy temporal lobe functioning for successful consolidation of procedural information, as well as the importance of seizure control for effective retention and consolidation of procedural memory.


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