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1. Activation of nicotinic acetylcholine receptors induces potentiation and synchronization within in vitro hippocampal networks

   https://doi.org/10.1111/jnc.14938  

   Djemil, Sarra ; Chen, Xin ; Zhang, Ziyue ; Lee, Jisoo ; Rauf, Mikael ; Pak, Daniel T. S. ; Dzakpasu, Rhonda ( December 2019 , Journal of Neurochemistry)

   Nicotinic acetylcholine receptors (nAChRs) are known to play a role in cognitive functions of the hippocampus, such as memory consolidation. Given that they conduct Ca²⁺and are capable of regulating the release of glutamate and γ‐aminobutyric acid (GABA) within the hippocampus, thereby shifting the excitatory‐inhibitory ratio, we hypothesized that the activation of nAChRs will result in the potentiation of hippocampal networks and alter synchronization. We used nicotine as a tool to investigate the impact of activation of nAChRs on neuronal network dynamics in primary embryonic rat hippocampal cultures prepared from timed‐pregnant Sprague‐Dawley rats. We perturbed cultured hippocampal networks with increasing concentrations of bath‐applied nicotine and performed network extracellular recordings of action potentials using a microelectrode array. We found that nicotine modulated network dynamics in a concentration‐dependent manner; it enhanced firing of action potentials as well as facilitated bursting activity. In addition, we used pharmacological agents to determine the contributions of discrete nAChR subtypes to the observed network dynamics. We found that β4‐containing nAChRs are necessary for the observed increases in spiking, bursting, and synchrony, while the activation of α7 nAChRs augments nicotine‐mediated network potentiation but is not necessary for its manifestation. We also observed that antagonists of N‐methyl‐D‐aspartate receptors (NMDARs) and group I metabotropic glutamate receptors (mGluRs) partially blocked the effects of nicotine. Furthermore, nicotine exposure promoted autophosphorylation of Ca²⁺/calmodulin‐dependent kinase II (CaMKII) and serine 831 phosphorylation of the α‐amino‐3‐hydroxy‐5‐methyl‐4‐isoxazolepropionic acid receptor (AMPAR) subunit GluA1. These results suggest that nicotinic receptors induce potentiation and synchronization of hippocampal networks and glutamatergic synaptic transmission. Findings from this work highlight the impact of cholinergic signaling in generating network‐wide potentiation in the form of enhanced spiking and bursting dynamics that coincide with molecular correlates of memory such as increased phosphorylation of CaMKII and GluA1.

   This article has received a badge for *Open Materials* because it provided all relevant information to reproduce the study in the manuscript. More information about the Open Practices badges can be found athttps://cos.io/our-services/open-science-badges/

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2. Neonicotinoids disrupt circadian rhythms and sleep in honey bees

   https://doi.org/10.1038/s41598-020-72041-3  

   Tackenberg, Michael C. ; Giannoni-Guzmán, Manuel A. ; Sanchez-Perez, Erik ; Doll, Caleb A. ; Agosto-Rivera, José L. ; Broadie, Kendal ; Moore, Darrell ; McMahon, Douglas G. ( December 2020 , Scientific Reports)

   Abstract Honey bees are critical pollinators in ecosystems and agriculture, but their numbers have significantly declined. Declines in pollinator populations are thought to be due to multiple factors including habitat loss, climate change, increased vulnerability to disease and parasites, and pesticide use. Neonicotinoid pesticides are agonists of insect nicotinic cholinergic receptors, and sub-lethal exposures are linked to reduced honey bee hive survival. Honey bees are highly dependent on circadian clocks to regulate critical behaviors, such as foraging orientation and navigation, time-memory for food sources, sleep, and learning/memory processes. Because circadian clock neurons in insects receive light input through cholinergic signaling we tested for effects of neonicotinoids on honey bee circadian rhythms and sleep. Neonicotinoid ingestion by feeding over several days results in neonicotinoid accumulation in the bee brain, disrupts circadian rhythmicity in many individual bees, shifts the timing of behavioral circadian rhythms in bees that remain rhythmic, and impairs sleep. Neonicotinoids and light input act synergistically to disrupt bee circadian behavior, and neonicotinoids directly stimulate wake-promoting clock neurons in the fruit fly brain. Neonicotinoids disrupt honey bee circadian rhythms and sleep, likely by aberrant stimulation of clock neurons, to potentially impair honey bee navigation, time-memory, and social communication. 

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3. NMDA receptors promote hippocampal sharp‐wave ripples and the associated coactivity of CA1 pyramidal cells

   https://doi.org/10.1002/hipo.23276  

   Howe, Timothy ; Blockeel, Anthony J. ; Taylor, Hannah ; Jones, Matthew W. ; Bazhenov, Maxim ; Malerba, Paola ( October 2020 , Hippocampus)

   Hippocampal sharp‐wave ripples (SWRs) support the reactivation of memory representations, relaying information to neocortex during “offline” and sleep‐dependent memory consolidation. While blockade of NMDA receptors (NMDAR) is known to affect both learning and subsequent consolidation, the specific contributions of NMDAR activation to SWR‐associated activity remain unclear. Here, we combine biophysical modeling with in vivo local field potential (LFP) and unit recording to quantify changes in SWR dynamics following inactivation of NMDAR. In a biophysical model of CA3‐CA1 SWR activity, we find that NMDAR removal leads to reduced SWR density, but spares SWR properties such as duration, cell recruitment and ripple frequency. These predictions are confirmed by experiments in which NMDAR‐mediated transmission in rats was inhibited using three different NMDAR antagonists, while recording dorsal CA1 LFP. In the model, loss of NMDAR‐mediated conductances also induced a reduction in the proportion of cell pairs that co‐activate significantly above chance across multiple events. Again, this prediction is corroborated by dorsal CA1 single‐unit recordings, where the NMDAR blocker ketamine disrupted correlated spiking during SWR. Our results are consistent with a framework in which NMDA receptors both promote activation of SWR events and organize SWR‐associated spiking content. This suggests that, while SWR are short‐lived events emerging in fast excitatory‐inhibitory networks, slower network components including NMDAR‐mediated currents contribute to ripple density and promote consistency in the spiking content across ripples, underpinning mechanisms for fine‐tuning of memory consolidation processes.

    

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4. Acoustic enhancement of sleep slow oscillations in mild cognitive impairment

   https://doi.org/10.1002/acn3.796  

   Papalambros, Nelly A. ; Weintraub, Sandra ; Chen, Tammy ; Grimaldi, Daniela ; Santostasi, Giovanni ; Paller, Ken A. ; Zee, Phyllis C. ; Malkani, Roneil G. ( July 2019 , Annals of Clinical and Translational Neurology)

   Slow‐wave activity (SWA) during sleep is reduced in people with amnestic mild cognitive impairment (aMCI) and is related to sleep‐dependent memory consolidation. Acoustic stimulation of slow oscillations has proven effective in enhancingSWAand memory in younger and older adults. In this study we aimed to determine whether acoustic stimulation during sleep boostsSWAand improves memory performance in people withaMCI.

   Nine adults withaMCI(72 ± 8.7 years) completed one night of acoustic stimulation (stim) and one night of sham stimulation (sham) in a blinded, randomized crossover study. Acoustic stimuli were delivered phase‐locked to the upstate of the endogenous sleep slow‐waves. Participants completed a declarative recall task with 44 word‐pairs before and after sleep.

   During intervals of acoustic stimulation,SWAincreased by >10% over sham intervals (P < 0.01), but memory recall increased in only five of the nine patients. The increase inSWAwith stimulation was associated with improved morning word recall (r = 0.78,P = 0.012).

   Acoustic stimulation delivered during slow‐wave sleep over one night was effective for enhancingSWAin individuals withaMCI. Given established relationships betweenSWAand memory, a larger or more prolonged enhancement may be needed to consistently improve memory inaMCI.

    

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5. Single closed‐loop acoustic stimulation targeting memory consolidation suppressed hippocampal ripple and thalamo‐cortical spindle activity in mice

   https://doi.org/10.1111/ejn.16116  

   Aksamaz, Sonat ; Mölle, Matthias ; Akinola, Esther Olubukola ; Gromodka, Erik ; Bazhenov, Maxim ; Marshall, Lisa ( August 2023 , European Journal of Neuroscience)

   Brain rhythms of sleep reflect neuronal activity underlying sleep‐associated memory consolidation. The modulation of brain rhythms, such as the sleep slow oscillation (SO), is used both to investigate neurophysiological mechanisms as well as to measure the impact of sleep on presumed functional correlates. Previously, closed‐loop acoustic stimulation in humans targeted to the SO Up‐state successfully enhanced the slow oscillation rhythm and phase‐dependent spindle activity, although effects on memory retention have varied. Here, we aim to disclose relations between stimulation‐induced hippocampo‐thalamo‐cortical activity and retention performance on a hippocampus‐dependent object‐place recognition task in mice by applying acoustic stimulation at four estimated SO phases compared to sham condition. Across the 3‐h retention interval at the beginning of the light phase closed‐loop stimulation failed to improve retention significantly over sham. However, retention during SO Up‐state stimulation was significantly higher than for another SO phase. At all SO phases, acoustic stimulation was accompanied by a sharp increase in ripple activity followed by about a second‐long suppression of hippocampal sharp wave ripple and longer maintained suppression of thalamo‐cortical spindle activity. Importantly, dynamics of SO‐coupled hippocampal ripple activity distinguished SOUp‐state stimulation. Non‐rapid eye movement (NREM) sleep was not impacted by stimulation, yet preREM sleep duration was effected. Results reveal the complex effect of stimulation on the brain dynamics and support the use of closed‐loop acoustic stimulation in mice to investigate the inter‐regional mechanisms underlying memory consolidation.

    

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