A metabolic function of the hippocampal sharp wave-ripple

Tingley, David; McClain, Kathryn; Kaya, Ekin; Carpenter, Jordan; Buzsáki, György

doi:10.1038/s41586-021-03811-w

Cited by 60 publications

(67 citation statements)

References 52 publications

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“…Moreover, many LS neurons display a postripple activation that correlates with ripple amplitude ( Wirtshafter and Wilson, 2019 ; Tingley and Buzsáki, 2020 ), further supporting a hippocampus→LS routing of information flow. Interestingly, hippocampal ripple oscillation appears to control the LS for parrel regulation of whole-body glucose homeostasis and memory consolidation ( Tingley et al, 2021 ). This line of evidence provides initial insight into the neural mechanism of hippocampus→dLS communication for memory consolidation.…”

Section: Ls-associated Circuitry In Memorymentioning

confidence: 99%

Putting Together Pieces of the Lateral Septum: Multifaceted Functions and Its Neural Pathways

Rizzi-Wise

Wang

2021

eNeuro

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The lateral septum (LS) is implicated as a hub that regulates a variety of affects, such as reward, feeding, anxiety, fear, sociability, and memory. However, it remains unclear how the LS, previously treated as a structure of homogeneity, exhibits such multifaceted functions. Emerging evidence suggests that different functions of the LS are mediated largely by its diverse input and output connections. It has also become clear that the LS is a heterogeneous region, where its dorsal and ventral poles play dissociable and often opposing roles. This functional heterogeneity can often be explained by distinct dorsal and ventral hippocampal inputs along the LS dorsoventral axis, as well as antagonizing connections between LS subregions. Similarly, outputs from LS subregions to respective downstream targets, such as hypothalamic, preoptic, and tegmental areas, also account for this functional heterogeneity. In this review, we provide an updated perspective on LS subregion classification, connectivity, and functions. We also identify key questions that have yet to be addressed in the field.

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Section: Ls-associated Circuitry In Memorymentioning

confidence: 99%

Putting Together Pieces of the Lateral Septum: Multifaceted Functions and Its Neural Pathways

Rizzi-Wise

Wang

2021

eNeuro

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“…We have demonstrated that cytokine signaling in the hippocampus can predict adiposity and glucose tolerance with high accuracy. Previous studies have also identified a link between systemic metabolism and hippocampal changes, where electrophysiological pulses (sharp waveripples) in the hippocampus regulate peripheral glucose concentration 43 . Communication between the hippocampus and systemic metabolism may involve autonomic innervation from the hippocampus to the pancreas and liver, or through hippocampal signaling to the hypothalamus 43 , a major metabolic control center in the brain.…”

Section: Discussionmentioning

confidence: 99%

“…Similarly, APOE4 alters lipid 36,37 , cholesterol 36 , and glucose metabolism in the brain 14,16,38,39 , but little is known about the influence of systemic metabolic function on molecular signaling networks in the brain in the context of APOE4 [40][41][42] . Previous studies have identified a link between systemic metabolism and hippocampal electrophysiology changes 43,44 , where communication between the hippocampus and periphery can involve autonomic innervation from the hippocampus to the pancreas and liver, as well as hippocampal signaling to the hypothalamus 43,45 , a major metabolic control center in the brain. An approach that identifies the relationships of APOE4 effects on systemic metabolic function and neuroinflammation together, instead of studying the brain and periphery as isolated systems, is necessary to define the disease-promoting environment created by the interacting effects of systemic metabolic dysfunction and neuroinflammation under the combined influence of APOE genotype and aging.…”

Section: Introductionmentioning

confidence: 99%

Predictive link between systemic metabolism and cytokine signatures in the brain of apolipoprotein E ε4 mice

Fleeman

Snyder

Kuhn

et al. 2022

Preprint

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The ϵ4 variant of apolipoprotein E (APOE) is the strongest and most common genetic risk factor for Alzheimer's disease (AD). While the mechanism of conveyed risk is incompletely understood, promotion of inflammation, dysregulated metabolism, and protein misfolding and aggregation have been implicated as potential contributions to accelerating disease. Here we determined the concurrent effects of systemic metabolic effects and brain inflammation in young (3-month-old) and aged (18-month-old) female mice carrying the human APOE4 gene. Using functional metabolic assays alongside multivariate modeling of hippocampal cytokine signaling, we found that immune signaling patterns in the brain are predictive of systemic metabolic outcomes, independent of AD proteinopathies. The relationship between cytokine signaling networks in the hippocampus and systemic glucose tolerance and adiposity differ by APOE genotype, where APOE4 mice produce lower levels of neuroprotective cytokines as they age and as their metabolic phenotype declines. To our knowledge, ours is the first study to identify a quantitative and predictive link between systemic metabolism and specific pathological immune signaling signatures in the brain. Our results highlight the AD-relevant effects of APOE4 beyond the brain and highlight the potential for bidirectional systemic influences of risk factors in the brain and periphery.

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“…Importantly, the presence of localized, concurrent ripple oscillations in the parietal cortex was recently observed in rats [34] possibly aiding information transfer from hippocampal to neocortical networks during memory consolidation. Interestingly, a recent study by Tingley and colleagues [52] found that hippocampal sharp wave-ripples additionally in uence metabolic processes, highlighting the embeddedness of brain function within the whole body [50,58] in which respiratory signals potentially serve a critical role [59].…”

Section: Discussionmentioning

confidence: 99%

Respiratory Entrainment of Units in the Mouse Parietal Cortex Depends on Vigilance State

Jung

Yanovsky

Brankačk

et al. 2022

Preprint

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Synchronous oscillations are essential for coordinated activity in neuronal networks and, hence, for behavior and cognition. While most network oscillations are generated within the central nervous system, recent evidence shows that rhythmic body processes strongly influence activity patterns throughout the brain. A major factor is respiration, which entrains multiple brain regions at the mesoscopic (local field potential) and single-cell levels. However, it is largely unknown how such respiration-driven rhythms interact or compete with internal brain oscillations, especially those with similar frequency domains. In mice, respiration and theta (θ) oscillations have overlapping frequencies and co-occur in various brain regions. Here we investigated the effects of respiration and θ on neuronal discharges in the mouse parietal cortex during four behavioral states which either show prominent θ (REM sleep and active waking (AW)) or lack significant θ (NREM sleep and waking immobility (WI)). We report a pronounced state-dependence of spike modulation by both rhythms. During REM sleep, θ effects on unit discharges dominate, while during AW respiration has a larger influence, despite the concomitant presence of θ oscillations. In most states, unit modulation by θ or respiration increases with mean firing rate. The preferred timing of respiration-entrained discharges (inspiration versus expiration) varies between states, indicating state-specific and different underlying mechanisms. Our findings show that neurons in an associative cortex area are differentially and state-dependently modulated by two fundamentally different processes: brain-endogenous θ oscillations and rhythmic somatic feedback signals from respiration.

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A metabolic function of the hippocampal sharp wave-ripple

Cited by 60 publications

References 52 publications

Putting Together Pieces of the Lateral Septum: Multifaceted Functions and Its Neural Pathways

Putting Together Pieces of the Lateral Septum: Multifaceted Functions and Its Neural Pathways

Predictive link between systemic metabolism and cytokine signatures in the brain of apolipoprotein E ε4 mice

Respiratory Entrainment of Units in the Mouse Parietal Cortex Depends on Vigilance State

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