Dose-dependent suppression of hippocampal contextual memory formation, place cells, and spatial engrams by the NMDAR antagonist (R)-CPP

Zhu, Mengwen; Perkins, Mark G.; Lennertz, Richard; Abdulzahir, Alifayaz; Pearce, Robert A.

doi:10.1016/j.neuropharm.2022.109215

Cited by 5 publications

(2 citation statements)

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“…However, spatial engrams differ from place cell maps and IEGdefined engrams (a collection of engram cells) in several important ways: i) they include both place cells and non-place cells; ii) they presumably include both engram cells and non-engram cells 59,80 ; and iii) they represent ensemble activity of a large proportion of the population rather than a restricted subset of highly active cells. These spatially modulated firing patterns, which other investigators who have used the same recording methods have also observed 55,56,64,81 , embody many of the characteristics expected of neuronal correlates of memory. These include the ability to retain stable representations of an environment over extended periods of time 55,64 , the ability to discriminate between arenas with different cues but at the same time to generalize between arenas in the same general environment 64 (and Fig.…”

Section: Discussionmentioning

confidence: 60%

Control of contextual memory through interneuronal α5-GABA_Areceptors

Zhu

Abdulzahir

Perkins

et al. 2022

Preprint

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Abstractγ-aminobutyric acid type A receptors that incorporate α5 subunits (α5-GABAARs) are highly enriched in the hippocampus and they are strongly implicated in the control of learning and memory. Receptors located on pyramidal neuron dendrites have long been considered responsible, but here we report that selective elimination of α5-GABAARs from either interneurons or pyramidal cells prevented the general anesthetic etomidate from suppressing contextual learning. Using Ca2+ imaging of hippocampal neuronal activity in freely exploring mice, we also found that etomidate interfered with the development of place cells and spatial engrams in wild type mice but not in interneuron-specific α5-GABAAR knockout mice. These findings show that α5-GABAARs on interneurons as well as pyramidal neurons mediate etomidate-induced amnesia.

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Section: Discussionmentioning

confidence: 60%

Control of contextual memory through interneuronal α5-GABA_Areceptors

Zhu

Abdulzahir

Perkins

et al. 2022

Preprint

Self Cite

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show abstract

“…However, spatial engrams differ from place cell maps and IEG-defined engrams (a collection of engram cells) in several important ways: (i) they include both place cells and nonplace cells; (ii) they presumably include both engram cells and nonengram cells ( 61 , 82 ); and (iii) they represent ensemble activity of a large proportion of the population rather than a restricted subset of highly active cells. These spatially modulated firing patterns, which other investigators who have used the same recording methods have also observed ( 57 , 58 , 66 , 83 ), embody many of the characteristics expected of neuronal correlates of memory. These include the ability to retain stable representations of an environment over extended periods of time ( 57 , 66 ), the ability to discriminate between arenas with different cues but at the same time to generalize between arenas in the same general environment ( 66 ) (Fig.…”

Section: Discussionmentioning

confidence: 55%

Control of contextual memory through interneuronal α5-GABAA receptors

et al. 2023

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γ-Aminobutyric acid type A receptors that incorporate α5 subunits (α5-GABAARs) are highly enriched in the hippocampus and are strongly implicated in control of learning and memory. Receptors located on pyramidal neuron dendrites have long been considered responsible, but here we report that mice in which α5-GABAARs have been eliminated from pyramidal neurons (α5-pyr-KO) continue to form strong spatial engrams and that they remain as sensitive as their pseudo-wild-type (p-WT) littermates to etomidate-induced suppression of place cells and spatial engrams. By contrast, mice with selective knockout in interneurons (α5-i-KO) no longer exhibit etomidate-induced suppression of place cells. In addition, the strength of spatial engrams is lower in α5-i-KO mice than p-WT littermates under control conditions. Consistent with the established role of the hippocampus in contextual fear conditioning, α5-i-KO mice resisted etomidate’s suppression of freezing to context, but so too did α5-pyr-KO mice, supporting a role for extra-hippocampal regions in the development of contextual fear memory. Overall, our results indicate that interneuronal α5-GABAARs serve a physiological role in promoting spatial learning and that they mediate suppression of hippocampus-dependent contextual memory by etomidate.

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Comparative Analysis of Excitatory and Inhibitory Hippocampal Neurons on Retrieval of Associative Contextual Memory

Toropova,

Ivashkina,

Vorobyeva

et al. 2024

Neurosci Behav Physi

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Dose-dependent suppression of hippocampal contextual memory formation, place cells, and spatial engrams by the NMDAR antagonist (R)-CPP

Cited by 5 publications

References 82 publications

Control of contextual memory through interneuronal α5-GABA_Areceptors

Control of contextual memory through interneuronal α5-GABA_Areceptors

Control of contextual memory through interneuronal α5-GABAA receptors

Comparative Analysis of Excitatory and Inhibitory Hippocampal Neurons on Retrieval of Associative Contextual Memory

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Dose-dependent suppression of hippocampal contextual memory formation, place cells, and spatial engrams by the NMDAR antagonist (R)-CPP

Cited by 5 publications

References 82 publications

Control of contextual memory through interneuronal α5-GABAAreceptors

Control of contextual memory through interneuronal α5-GABAAreceptors

Control of contextual memory through interneuronal α5-GABAA receptors

Comparative Analysis of Excitatory and Inhibitory Hippocampal Neurons on Retrieval of Associative Contextual Memory

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Control of contextual memory through interneuronal α5-GABA_Areceptors

Control of contextual memory through interneuronal α5-GABA_Areceptors