Ripple-selective GABAergic projection cells in the hippocampus

Szabó, Gergely; Farrell, Jordan S.; Dudok, Barna; Hou, Wen-Hsien; Ortiz, Anna L.; Varga, Csaba; Moolchand, Prannath; Gulsever, Cafer Ikbal; Gschwind, Tilo; Dimidschstein, Jordane; Capogna, Marco; Soltész, Iván

doi:10.1016/j.neuron.2022.04.002

Cited by 35 publications

(47 citation statements)

References 114 publications

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“…We hypothesized that synaptic depression from CA3 onto deep cells should reduce their firing rates in SWRs, while potentiation onto superficial cells should elevate their firing rates. In pre-experience SWRs, we observed a basal difference in the firing rates of deep and superficial neurons, consistent with the previously described impact of local inhibitory circuitry 41,61 . Deep CA1 neurons significantly reduced their firing rate from pre- to post-experience SWRs, while superficial neurons significantly increased their firing rate, consistent with opposite changes in their synaptic drive from area CA3 (Figure 4 E).…”

Section: Resultssupporting

confidence: 90%

Section: Exploration Induces Bidirectional Effects On Deep and Superf...supporting

confidence: 90%

“…These changes are reflected in the relative activity of these two groups during CA3-driven SWRs following a salient experience. Together with prior work 41,61 , our findings suggest a network model in which activity during exploration drives synaptic potentiation at CA3-to-superficial-CA1 synapses, resulting in elevated rates of superficial cell participation and firing rates in post-experience SWRs, while in vivo activity depresses CA3 input to deep pyramidal neurons, resulting in a reduction of firing rate and a relative suppression of participation of this cell population in SWRs.…”

Section: Discussionsupporting

confidence: 78%

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Bidirectional synaptic changes in deep and superficial hippocampal neurons followingin vivoactivity

Berndt

Trusel

Roberts

et al. 2022

Preprint

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Neuronal activity during experience is thought to induce plastic changes within the hippocampal network which underlie memory formation, although the extent and details of such changes in vivo remain unclear. Here, we employed a temporally precise marker of neuronal activity, CaMPARI2, to label active CA1 hippocampal neurons in vivo, followed by immediate acute slice preparation and electrophysiological quantification of synaptic properties. Recently active neurons in the superficial sublayer of stratum pyramidale displayed larger post-synaptic responses at excitatory synapses from area CA3, with no change in pre-synaptic release probability. In contrast, in vivo activity weakened both pre- and post-synaptic excitatory weights onto pyramidal cells in the deep sublayer. In vivo activity of deep and superficial neurons within sharp-wave ripples was bidirectionally changed across experience, consistent with the observed changes in synaptic weights. These findings reveal novel, fundamental mechanisms through which the hippocampal network is modified by experience to store information.

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Section: Resultssupporting

confidence: 90%

Section: Exploration Induces Bidirectional Effects On Deep and Superf...supporting

confidence: 90%

Section: Discussionsupporting

confidence: 78%

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Bidirectional synaptic changes in deep and superficial hippocampal neurons followingin vivoactivity

Berndt

Trusel

Roberts

et al. 2022

Preprint

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“…Another subtype of hippocampal inhibitory interneuron that target other local interneurons and have long-range projections that could be implicated in "reward on" responses are the so-called TORO (theta-OFF/ripple ON) cells. The activity of TORO cells is negatively correlated with animal speed and locomotion, and some TORO cells were identified as SOM-INs (47). However, more definite evidence of cell type-specific SOM-IN responses related to reward location will require recording and manipulating activity from identified hippocampal SOM-IN subtypes in goal-oriented spatial memory tasks.…”

Section: Heterogeneity Of Som-in Ca 2+ Responsesmentioning

confidence: 99%

mTORC1-mediated acquisition of reward-related spatial representations by hippocampal somatostatin interneuronsa

Michon

Laplante

Bosson

et al. 2023

Preprint

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Plasticity of principal cells and inhibitory interneurons underlies hippocampal memory. Bidirectional modulation of somatostatin cell mTORC1 activity, a crucial translational control mechanism in synaptic plasticity, causes parallel changes in hippocampal CA1 somatostatin interneuron (SOM-IN) long-term potentiation and hippocampus-dependent memory, indicating a key role in learning. However, SOM-IN activity changes and behavioral correlates during learning, and the role of mTORC1 in these processes, remain ill-defined. To address these questions, we used two-photon Ca2+ imaging from SOM-INs during a virtual reality goal-directed spatial memory task in head-fixed control mice (SOM-IRES-Cre mice) or in mice with conditional knockout of Rptor (SOM-Rptor-KO mice) to block mTORC1 activity in SOM-INs. We found that control mice learn the task, but SOM-Raptor-KO mice exhibit a deficit. Also, SOM-IN Ca2+ activity became increasingly related to reward localization during learning in control mice but not in SOM-Rptor-KO mice. Four types of SOM-IN activity patterns related to reward location were observed, "reward off sustained", "reward off transient", "reward on sustained" and "reward on transient", and these responses showed global remapping after reward relocation in control but not SOM-Rptor-KO mice. Thus, SOM-INs develop mTORC1-dependent spatial coding related to learning reward localization. This coding may bi-directionally interact with pyramidal cells and other structures to represent and consolidate reward location.

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“…For example, in CA1, a subregion of the hippocampus, there are >20 types of inhibitory neurons identified ( Freund and Buzsáki, 1996 ; Klausberger and Somogyi, 2008 ). Recent work has identified and characterized additional CA1 populations, and genomic analysis suggests that even more populations remain poorly characterized ( Francavilla et al, 2018 ; Harris et al, 2018 ; Christenson Wick et al, 2019 ; Yao et al, 2021 ; Szabo et al, 2022 ). Each interneuron subtype has distinct properties and roles, subsequently forming unique microcircuits in healthy and epileptic tissue ( Alexander et al, 2016 ; Booker and Vida, 2018 ; Shuman et al, 2020 ; Dudok et al, 2021 ; Righes Marafiga et al, 2021 ).…”

Section: Introductionmentioning

confidence: 99%

LINCs Are Vulnerable to Epileptic Insult and Fail to Provide Seizure Control via On-Demand Activation

Stieve

Smith

Krook-Magnuson

2023

eNeuro

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Temporal lobe epilepsy (TLE) is notoriously pharmacoresistant, and identifying novel therapeutic targets for controlling seizures is crucial. LINCs, a population of hippocampal neurons, were recently identified as a unique source of widespread inhibition in CA1, able to elicit both GABAA- and GABAB-mediated postsynaptic inhibition. We therefore hypothesized that LINCs could be an effective target for seizure control. LINCs were optogenetically activated for on-demand seizure intervention in the intrahippocampal kainate (IHKA) mouse model of chronic TLE. Unexpectedly, LINC activation at one month post-KA did not substantially reduce seizure duration in either male or female mice. We tested two different sets of stimulation parameters, both previously found to be effective with on-demand optogenetic approaches, but neither was successful. Quantification of LINCs following intervention revealed a substantial reduction of LINC numbers compared to saline-injected controls. We also observed a decreased number of LINCs when the site of initial insult (i.e. KA injection) was moved to the amygdala (BLA-KA), and correspondingly, no effect of light delivery on BLA-KA seizures. This indicates that LINCs may be a vulnerable population in TLE, regardless of the site of initial insult. To determine whether long-term circuitry changes could influence outcomes, we continued testing once a month for up to 6 months post-KA. However, at no time point did LINC activation provide meaningful seizure suppression. Altogether, our results suggest that LINCs are not a promising target for seizure inhibition in TLE.Significance StatementNovel treatments are needed for temporal lobe epilepsy, and altering inhibitory signaling may provide seizure control. Recently, a previously uncharacterized hippocampal cell population, LINCs, was found to provide strong, widespread, inhibition in healthy tissue. Despite being a novel source of powerful inhibition, and therefore a promising candidate for seizure control, on-demand activation of LINCs in a mouse model of temporal lobe epilepsy did not substantially suppress seizure activity. LINC numbers were decreased in epileptic tissue, indicating that LINCs are a vulnerable cell population. The heterogeneity of inhibitory signaling, and how it changes in epilepsy, are important factors to consider when developing new temporal lobe epilepsy therapies.

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Ripple-selective GABAergic projection cells in the hippocampus

Cited by 35 publications

References 114 publications

Bidirectional synaptic changes in deep and superficial hippocampal neurons followingin vivoactivity

Bidirectional synaptic changes in deep and superficial hippocampal neurons followingin vivoactivity

mTORC1-mediated acquisition of reward-related spatial representations by hippocampal somatostatin interneuronsa

LINCs Are Vulnerable to Epileptic Insult and Fail to Provide Seizure Control via On-Demand Activation

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