Dentate gyrus and CA3 GABAergic interneurons bidirectionally modulate signatures of internal and external drive to CA1

Jones, Emily A Aery; Rao, Antara; Zilberter, Misha; Djukic, Biljana; Bant, Jason S.; Gillespie, Anna K.; Koutsodendris, Nicole; Nelson, Maxine; Yoon, Seo Yeon; Huang, Ky; Yuan, Heidi; Gill, Theodore M; Huang, Yadong; Frank, Loren M.

doi:10.1016/j.celrep.2021.110159

Cited by 18 publications

(9 citation statements)

References 111 publications

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“…Another metric that showed minimal variation was the DS width measure proposed in this study. Unlike conventional width measurements that rely on amplitude [15,27,30], our proposed metric takes into account the dynamics of the average waveform, specifically the temporal distance between the second upward concavities around the peak. Further By using the scaled peak amplitude and the width of the mean waveforms, we compared morphological features between the DS types classified by WFbC in the transgenic mice, which represented an AD model (ApoE4-KI) and the control group (ApoE3-KI) across different ages.…”

Section: Discussionmentioning

confidence: 99%

“…Dataset C is composed of the 0-300 Hz filtered LFPs from two parvalbumin-expressing (PV)-Cre mice and two somatostatin-expressing (SST)-Cre mice within their home cages, as described in [30]. Here we analyzed the concatenated LFPs from the sessions with vehicle (1% dimethyl sulfoxide in 0.9% sterile saline) administration [30]. The implanted 32-site linear probes had a distance of 50 µm between electrodes.…”

Section: Wfbc Validation Datasetsmentioning

confidence: 99%

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Waveform-based classification of dentate spikes

Santiago,

Lopes-dos-Santos,

Jones

et al. 2023

Preprint

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Synchronous excitatory discharges from the entorhinal cortex (EC) to the dentate gyrus (DG) generate fast and prominent patterns in the hilar local field potential (LFP), called dentate spikes (DSs). As sharp-wave ripples in CA1, DSs are more likely to occur in quiet behavioral states, when memory consolidation is thought to take place. However, their functions in mnemonic processes are yet to be elucidated. The classification of DSs into types 1 or 2 is determined by their origin in the lateral or medial EC, as revealed by current source density (CSD) analysis, which requires recordings from linear probes with multiple electrodes spanning the DG layers. To allow the investigation of the functional role of each DS type in recordings obtained from single electrodes and tetrodes, which are abundant in the field, we developed an unsupervised method using Gaussian mixture models to classify such events based on their waveforms. Our classification approach achieved high accuracies (> 80%) when validated in 8 mice with DG laminar profiles. The average CSDs, waveforms, rates, and widths of the DS types obtained through our method closely resembled those derived from the CSD-based classification. As an example of application, we used the technique to analyze single-electrode LFPs from apolipoprotein (apo) E3 and apoE4 knock-in mice. We observed that the latter group, which is a model for Alzheimer's disease, exhibited wider DSs of both types from a young age, with a larger effect size for DS type 2, likely reflecting early pathophysiological alterations in the EC-DG network, such as hyperactivity. In addition to the applicability of the method in expanding the study of DS types, our results show that their waveforms carry information about their origins, suggesting different underlying network dynamics and roles in memory processing.

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Section: Discussionmentioning

confidence: 99%

Section: Wfbc Validation Datasetsmentioning

confidence: 99%

Waveform-based classification of dentate spikes

Santiago,

Lopes-dos-Santos,

Jones

et al. 2023

Preprint

Self Cite

View full text Add to dashboard Cite

show abstract

“…Dataset C is composed of the 0–300 Hz filtered LFPs from two parvalbumin-expressing (PV)-Cre mice and two somatostatin-expressing (SST)-Cre mice within their home cages, as previously described 30 . Here we analyzed the concatenated LFPs from the sessions with vehicle (1% dimethyl sulfoxide in 0.9% sterile saline) administration 30 . The implanted 32-site linear probes had a distance of 50 µm between electrodes.…”

Section: Methodsmentioning

confidence: 99%

“…Beyond calculating the WFbC accuracy, we also compared DS occurrence and morphological metrics of the DS types classified by both methods. In the process, we developed a new approach to measure the DS width based on waveform dynamics that was consistent across the DG layers, therefore serving as an alternative to traditional amplitude-based metrics 15 , 27 , 30 .…”

Section: Introductionmentioning

confidence: 99%

Waveform-based classification of dentate spikes

Santiago,

Lopes-dos-Santos,

Aery Jones

et al. 2024

Sci Rep

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Synchronous excitatory discharges from the entorhinal cortex (EC) to the dentate gyrus (DG) generate fast and prominent patterns in the hilar local field potential (LFP), called dentate spikes (DSs). As sharp-wave ripples in CA1, DSs are more likely to occur in quiet behavioral states, when memory consolidation is thought to take place. However, their functions in mnemonic processes are yet to be elucidated. The classification of DSs into types 1 or 2 is determined by their origin in the lateral or medial EC, as revealed by current source density (CSD) analysis, which requires recordings from linear probes with multiple electrodes spanning the DG layers. To allow the investigation of the functional role of each DS type in recordings obtained from single electrodes and tetrodes, which are abundant in the field, we developed an unsupervised method using Gaussian mixture models to classify such events based on their waveforms. Our classification approach achieved high accuracies (> 80%) when validated in 8 mice with DG laminar profiles. The average CSDs, waveforms, rates, and widths of the DS types obtained through our method closely resembled those derived from the CSD-based classification. As an example of application, we used the technique to analyze single-electrode LFPs from apolipoprotein (apo) E3 and apoE4 knock-in mice. We observed that the latter group, which is a model for Alzheimer’s disease, exhibited wider DSs of both types from a young age, with a larger effect size for DS type 2, likely reflecting early pathophysiological alterations in the EC-DG network, such as hyperactivity. In addition to the applicability of the method in expanding the study of DS types, our results show that their waveforms carry information about their origins, suggesting different underlying network dynamics and roles in memory processing.

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“…In the hippocampal CA3, the inhibitory interneurons participate in the performance of cognitive functions by regulating the balance of synaptic excitation/inhibition and neuronal synchronization 10,11 . More importantly, PV interneurons are one of the most important GABAergic inhibitory interneurons in the hippocampus 12 and play an important role in the production of gamma oscillations 13 . Accumulating evidence shows that the dysfunction of PV interneurons resulting in disturbed LFP‐gamma oscillations is associated with the pathogenesis of cognitive disorders 14‐16 .…”

Section: Introductionmentioning

confidence: 99%

SynCAM1 deficiency in the hippocampal parvalbumin interneurons contributes to sevoflurane‐induced cognitive impairment in neonatal rats

Zhao,

Gu,

Pan

et al. 2023

CNS Neurosci Ther

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AimsSevoflurane is widely used for general anesthesia in children. Previous studies reported that multiple neonatal exposures to sevoflurane can induce long‐term cognitive impairment in adolescent rats, but the underlying mechanisms were not defined.MethodsPostnatal day 6 (P6) to P8 rat pups were exposed to 30% oxygen with or without 3% sevoflurane balanced with air. The Y maze test (YMT) and Morris water maze (MWM) tests were performed in some cohorts from age P35 to assess cognitive functions, and their brain samples were harvested at age P14, 21, 28, 35, and 42 for measurements of various molecular entities and in vivo electrophysiology experiments at age P35.ResultsSevoflurane exposure resulted in cognitive impairment that was associated with decreased synCAM1 expression in parvalbumin (PV) interneurons, a reduction of PV phenotype, disturbed gamma oscillations, and dendritic spine loss in the hippocampal CA3 region. Enriched environment (EE) increased synCAM1 expression in the PV interneurons and attenuated sevoflurane‐induced cognitive impairment. The synCAM1 overexpression by the adeno‐associated virus vector in the hippocampal CA3 region restored sevoflurane‐induced cognitive impairment, PV phenotype loss, gamma oscillations decrease, and dendritic spine loss.ConclusionOur data suggested that neonatal sevoflurane exposure results in cognitive impairment through decreased synCAM1 expression in PV interneurons in the hippocampus.

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Dentate gyrus and CA3 GABAergic interneurons bidirectionally modulate signatures of internal and external drive to CA1

Cited by 18 publications

References 111 publications

Waveform-based classification of dentate spikes

Waveform-based classification of dentate spikes

Waveform-based classification of dentate spikes

SynCAM1 deficiency in the hippocampal parvalbumin interneurons contributes to sevoflurane‐induced cognitive impairment in neonatal rats

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