Hippocampal sharp waves and ripples: Effects of aging and modulation by NMDA receptors and L-type Ca2+ channels

Kouvaros, Stylianos; Kotzadimitriou, Dimitrios; Papatheodoropoulos, Costas

doi:10.1016/j.neuroscience.2015.04.012

Cited by 12 publications

(9 citation statements)

References 91 publications

(114 reference statements)

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“…In hippocampal slices, NMDAR inhibition with the noncompetitive antagonist MK‐801 results in enhanced SWR detection (Colgin et al, 2005; Kouvaros et al, 2015), in contrast to our main result. While the reduction of the circuitry only to the CA3‐CA1 regions in slices makes them comparable to our computational model, in our model we do not capture the intracellular complexities of calcium signaling and only focus on the effects of NMDA depolarizing currents on network dynamics, while cascade effects of calcium signaling have been implicated as the explanation for the over‐representation of SWRs in MK‐801 slices.…”

Section: Discussioncontrasting

confidence: 91%

Section: Discussionmentioning

confidence: 99%

“…given its utility as a rapid-acting antidepressant (Berman et al, 2000;Price, Nock, Charney, & Mathew, 2009). However, the interrelations In hippocampal slices, NMDAR inhibition with the noncompetitive antagonist MK-801 results in enhanced SWR detection (Colgin et al, 2005;Kouvaros et al, 2015) (Chang, Hsiao, Chen, Yu, & Gean, 2015;McDonald et al, 2005) or via channel blockers (MK801 (Girardeau et al, 2014;Norimoto et al, 2018), PCP (Ma & Leung, 2000), ketamine (Yang, Ju, Zhang, & Sun, 2018) (Girardeau et al, 2014) and spike content (Norimoto et al, 2018) as directly comparable to controls. A caveat of all systemic NMDAR blockers is that at low doses they are wake-promoting, hyperactivity-inducing substances, complicating the study of SWR, which occur predominantly (but not solely) during sleep.…”

Section: Discussionmentioning

confidence: 99%

“…There are multiple ways to experimentally block NMDAR transmission, including genetically (Norimoto et al, 2018; Shimizu, Tang, Rampon, & Tsien, 2000; Tonegawa et al, 1996; Tsien et al, 1996) and pharmacologically (Colgin, Jia, Sabatier, & Lynch, 2005; Girardeau et al, 2014; Kouvaros, Kotzadimitriou, & Papatheodoropoulos, 2015); and consequences of NMDAR blockade on network activity are bound to be widespread and layered. Our choice of systemic injections was driven by broader interest in understanding the consequences of NMDA hypofunction, which is widely implicated in psychiatric disorders (Coyle, 2012).…”

Section: Discussionmentioning

confidence: 99%

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

et al. 2020

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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 NMDARmediated 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 finetuning of memory consolidation processes.

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Section: Discussioncontrasting

confidence: 91%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

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

et al. 2020

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“…Further studies found that the increased Ca 2+ could result in neuronal apoptosis mainly through the activation of nitric oxide synthase, Ca 2+ sensitive protease, and mitochondrial damage (Kumar et al, 2014). Other studies have demonstrated that free radicals and oxidative stress also play an important role in excitotoxicity (Im et al, 2012;Yuki et al, 2013) and that the generation of free radicals is correlated with Ca 2+ (Kouvaros et al, 2015).…”

Section: Introductionmentioning

confidence: 97%

NMDA Receptor-Mediated Excitotoxicity Is Involved in Neuronal Apoptosis and Cognitive Impairment Induced by Chronic Hypobaric Hypoxia Exposure at High Altitude

Zhang

et al. 2021

High Altitude Medicine & Biology

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Ji, Weizhong, Yaqing Zhang, Ri-li Ge, Yaqi Wan, and Jie Liu. NMDA receptor-mediated excitotoxicity is involved in neuronal apoptosis and cognitive impairment induced by chronic hypobaric hypoxia exposure at high altitude. High Alt Med Biol. 22:45-57, 2021. Aim: Exposure to chronic hypobaric hypoxia at high altitude can lead to cognitive impairment; however, its underlying mechanism is still unclear. Excessive expression of glutamate and its receptors can induce excitotoxicity and cause neuronal necrosis, which is an important causative factor for the occurrence of various diseases in the nervous system. Therefore, excitotoxicity may also occur after exposure to a chronic hypobaric hypoxic environment. This study concentrates on the action mechanism of glutamate and its receptor-mediated excitotoxicity in cognitive impairment, induced by chronic hypobaric hypoxic exposure. Methods: Sprague-Dawley rats were fed at regions with three different altitudes (4,300, 2,260, and 450 m) for 8 weeks, and had their behavioral changes assessed by the Morris water maze test. Morphological, molecular biological, and biochemical tests were used to determine the role of N-methyl-d-aspartate (NMDA) receptor-mediated excitotoxicity in neuronal injury and cognitive impairment induced by chronic hypobaric hypoxia exposure. Results: We found that exposure to chronic hypobaric hypoxia at high altitudes could cause cognitive impairment, damage the neurons in the hippocampus and cortex, increase apoptosis, and lead to abnormal Caspase-3 protein expression. The expression of NMDA and a-amino-3-hydroxyl-5-methyl-4-isoxazole acid (AMPA) receptors increased significantly, as did the levels of oxidative stress and free radicals as well. However, no change in cognitive function was observed in the chronic hypobaric hypoxia environment at the middle altitude, there were no statistically significant differences in neuronal apoptosis and related protein expression compared with the rats in the flatland environment group. Conclusion:We show that high-altitude chronic hypobaric hypoxic environment could cause obvious cognitive impairments, which is related to the excitotoxicity mediated by glutamate and its receptors, in contrast to the chronic hypobaric hypoxia environment at middle altitude group and flatland environment group.

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Hippocampal Sharp Wave/Ripple Complexes—Physiology and Mechanisms

Maier

Kempter

2017

Cognitive Neuroscience of Memory Consolidation

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Hippocampal sharp waves and ripples: Effects of aging and modulation by NMDA receptors and L-type Ca2+ channels

Cited by 12 publications

References 91 publications

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

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

NMDA Receptor-Mediated Excitotoxicity Is Involved in Neuronal Apoptosis and Cognitive Impairment Induced by Chronic Hypobaric Hypoxia Exposure at High Altitude

Hippocampal Sharp Wave/Ripple Complexes—Physiology and Mechanisms

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