CA2 inhibition reduces the precision of hippocampal assembly reactivation

He, Hongshen; Boehringer, Roman; Huang, Arthur; Overton, Eric T. N.; Polygalov, Denis; Okanoya, Kazuo; McHugh, Thomas J.

doi:10.1101/2020.11.26.400655

Cited by 9 publications

(23 citation statements)

References 60 publications

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“…CA2 neurons may directly activate CA1 interneurons while triggering SWRs in the CA3 region, producing a multisynaptic delay of excitation 50 . Consistent with the possible inhibitory role of CA2 pyramidal cells, their chemogenetic silencing facilitates reactivation of CA1 cell assemblies while it reduces the temporal precision of the reactivation, often advancing the reactivation times 51 .…”

Section: Discussionmentioning

confidence: 78%

Inhibition allocates spikes during hippocampal ripples

et al. 2022

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Sets of spikes emitted sequentially across neurons constitute fundamental pulse packets in neural information processing, including offline memory replay during hippocampal sharp-wave ripples (SWRs). The relative timing of neuronal spikes is fine-tuned in each spike sequence but can vary between different sequences. However, the microcircuitry mechanism that enables such flexible spike sequencing remains unexplored. We recorded the membrane potentials of multiple hippocampal CA1 pyramidal cells in mice and found that the neurons were transiently hyperpolarized prior to SWRs. The pre-SWR hyperpolarizations were spatiotemporally heterogeneous, and larger hyperpolarizations were associated with later spikes during SWRs. Intracellular blockade of Cl−-mediated inhibition reduced pre-SWR hyperpolarizations and advanced spike times. Single-unit recordings also revealed that the pre-SWR firing rates of inhibitory interneurons predicted the SWR-relevant spike times of pyramidal cells. Thus, pre-SWR inhibitory activity determines the sequential spike times of pyramidal cells and diversifies the repertoire of sequence patterns.

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Section: Discussionmentioning

confidence: 78%

Inhibition allocates spikes during hippocampal ripples

et al. 2022

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“…Importantly, this work does not refute that of prior studies which showed a lack of current goal representation in ripples (Carey et al, 2019;Gillespie et al, 2021), but rather argues for a more nuanced view of hippocampal ripples as a flexible mechanism that may be capable of altering their information content based on the cognitive demands of the current task. The transition from unstructured ripples to spatially organized replay across the first few trials argues that experience-dependent synaptic plasticity, perhaps across the CA3 or CA2 networks (He et al, 2021), is necessary to coordinate replay, even in a familiar environment.…”

Section: Discussionmentioning

confidence: 99%

Spatial Learning Drives Rapid Goal Representation in Hippocampal Ripples without Place Field Accumulation or Goal-Oriented Theta Sequences

Pfeiffer

2022

J. Neurosci.

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The hippocampus is critical for rapid acquisition of many forms of memory, although the circuit-level mechanisms through which the hippocampus rapidly consolidates novel information are unknown. Here, the activity of large ensembles of hippocampal neurons in adult male Long-Evans rats was monitored across a period of rapid spatial learning to assess how the network changes during the initial phases of memory formation and retrieval. In contrast to several reports, the hippocampal network did not display enhanced representation of the goal location via accumulation of place fields or elevated firing rates at the goal. Rather, population activity rates increased globally as a function of experience. These alterations in activity were mirrored in the power of the theta oscillation and in the quality of theta sequences, without preferential encoding of paths to the learned goal location. In contrast, during brief "offline" pauses in movement, representation of a novel goal location emerged rapidly in ripples, preceding other changes in network activity. These data demonstrate that the hippocampal network can facilitate active navigation without enhanced goal representation during periods of active movement, and further indicate that goal representation in hippocampal ripples before movement onset supports subsequent navigation, possibly through activation of downstream cortical networks.

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“…Although relatively small, the CA2 subfield is of particular interest as it forms the nexus of a powerfully excitatory disynaptic circuit that directly links cortical input to hippocampal output (Chevaleyre & Siegelbaum, 2010; Srinivas et al, 2017). Furthermore, accumulating evidence suggests that CA2 may have a unique role regulating hippocampal network excitability and organizing population activity (Boehringer et al, 2017; He et al, 2021; Lehr et al, 2021; Oliva, Fernández-Ruiz, Buzsáki, & Berényi, 2016; Oliva, Fernández-Ruiz, Leroy, & Siegelbaum, 2020). Recordings from surgically-resected hippocampal tissue from patients with refractory TLE revealed spontaneous interictal-like spikes in CA2, but the study could not address whether CA2 activity contributes to spontaneous recurring seizures (Wittner et al, 2009).…”

Section: Introductionmentioning

confidence: 99%

Enhanced excitability of the hippocampal CA2 region and its contribution to seizure generation in a mouse model of temporal lobe epilepsy

Whitebirch

LaFrancois

Jain

et al. 2022

Preprint

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The hippocampal CA2 region, an area important for social memory, has been suspected to play a role in temporal lobe epilepsy (TLE) because of its resistance to the degeneration observed in neighboring CA1 and CA3 regions in both human and rodent models of TLE. However, little is known about whether alterations in CA2 properties serve to promote seizure generation or propagation. Here we have used the pilocarpine-induced status epilepticus (PILO-SE) model of TLE to explore the role of CA2. Ex vivo electrophysiological recordings from acute hippocampal slices revealed a set of coordinated changes that enhance CA2 intrinsic excitability, reduce CA2 local inhibitory input, and increase CA2 excitatory output to its major CA1 synaptic target. Moreover, selective silencing of CA2 pyramidal cells using a chemogenetic approach caused a significant decrease in the frequency of spontaneous seizures. These findings provide the first evidence that CA2 actively contributes to TLE seizure activity and may thus be a promising therapeutic target.

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CA2 inhibition reduces the precision of hippocampal assembly reactivation

Cited by 9 publications

References 60 publications

Inhibition allocates spikes during hippocampal ripples

Inhibition allocates spikes during hippocampal ripples

Spatial Learning Drives Rapid Goal Representation in Hippocampal Ripples without Place Field Accumulation or Goal-Oriented Theta Sequences

Enhanced excitability of the hippocampal CA2 region and its contribution to seizure generation in a mouse model of temporal lobe epilepsy

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