Mouse hippocampal CA1 VIP interneurons detect novelty in the environment and support recognition memory

Tamboli, Suhel; Singh, Sanjay; Topolnik, Dimitry; El Amine Barkat, Mohamed; Radhakrishnan, Risna; Guet-McCreight, Alexandre; Topolnik, Lisa

doi:10.1016/j.celrep.2024.114115

Cited by 9 publications

(2 citation statements)

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“…If the behavioral task-dependent shifts in the recruitment of O/A INs are associated with alterations in I-S3 excitability, they should be most pronounced during tasks that notably elevate the I-S3 cells’ activity. I-S3 cells are engaged in spatial decision-making, object coding and goal-directed behavior (Magnin et al, 2019; Turi et al, 2019; Tamboli et al, 2024). Consistent with the enhanced recruitment of these cells in the D-zone during spatial navigation and their positive modulation by objects (Tamboli et al, 2024), the activity of O/A INs was specifically enhanced during these behavioral patterns.…”

Section: Discussionmentioning

confidence: 99%

“…I-S3 cells are engaged in spatial decision-making, object coding and goal-directed behavior (Magnin et al, 2019; Turi et al, 2019; Tamboli et al, 2024). Consistent with the enhanced recruitment of these cells in the D-zone during spatial navigation and their positive modulation by objects (Tamboli et al, 2024), the activity of O/A INs was specifically enhanced during these behavioral patterns. Conversely, while I-S3 cells are modulated by animal running speed (Turi et al, 2019; Luo et al, 2020), no discernible alterations in the activity of O/A INs were noted during walking periods.…”

Section: Discussionmentioning

confidence: 99%

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Altered firing output of VIP interneurons and early dysfunctions in CA1 hippocampal circuits in the 3xTg mouse model of Alzheimer’s disease

Michaud,

Francavilla,

Topolnik

et al. 2024

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Alzheimer's disease (AD) leads to progressive memory decline, and alterations in hippocampal function are among the earliest pathological features observed in human and animal studies. GABAergic interneurons (INs) within the hippocampus coordinate network activity, among which type 3 interneuron-specific (I-S3) cells expressing vasoactive intestinal polypeptide and calretinin play a crucial role. These cells provide primarily disinhibition to principal excitatory cells (PCs) in the hippocampal CA1 region, regulating incoming inputs and memory formation. However, it remains unclear whether AD pathology induces changes in the activity of I-S3 cells, impacting the hippocampal network motifs. Here, using young adult 3xTg-AD mice, we found that while the density and morphology of IS-3 cells remain unaffected, there were significant changes in their firing output. Specifically, I-S3 cells displayed elongated action potentials and decreased firing rates, which was associated with a reduced inhibition of CA1 INs and their higher recruitment during spatial decision-making and object exploration tasks. Furthermore, the activation of CA1 PCs was also impacted, signifying early disruptions in CA1 network functionality. These findings suggest that altered firing patterns of I-S3 cells might initiate early-stage dysfunction in hippocampal CA1 circuits, potentially influencing the progression of AD pathology.

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