Functionally-distinct pyramidal cell subpopulations during gamma oscillations in mouse hippocampal area CA3

Balleza-Tapia, Hugo; Arroyo-García, Luis Enrique; Isla, Arturo G.; Loera-Valencia, Raúl; Fisahn, André

doi:10.1016/j.pneurobio.2021.102213

Cited by 6 publications

(1 citation statement)

References 35 publications

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“…Firing and membrane potential properties were recorded in gap-free current-clamp mode. Each cell classified as FSI underwent consequent hyper-and de-polarizing current steps (Input resistance protocol [34]: 25 steps of 10pA from -100pA to +140pA, 700ms each; Fig 2 .A) starting from the membrane resting potential and from a -70mV membrane potential. After recording, the slice was stored in PFA overnight and then in a 30% sucrose solution until further experiments.…”

Section: -Intrinsic Properties Of Fast-spiking Interneuronsmentioning

confidence: 99%

Association of microglia loss with hippocampal network impairments as a turning point in the amyloid pathology progression

Pizzirusso,

Preka,

Goikolea

et al. 2024

Preprint

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Alzheimer’s disease is a progressive neurological disorder causing memory loss and cognitive decline. The underlying causes of cognitive deterioration and neurodegeneration remain unclear, leading to a lack of effective strategies to prevent dementia. Recent evidence highlights the role of neuroinflammation, particularly involving microglia, in Alzheimer’s disease onset and progression. Characterizing the initial phase of Alzheimer’s disease can lead to the discovery of new biomarkers and therapeutic targets, facilitating timely interventions for effective treatments. We used theAppNL-G-Fknock-in mouse model, which resembles the amyloid pathology and neuroinflammatory characteristics of Alzheimer’s disease, to investigate the transition from a pre-plaque to an early plaque stage with a combined functional and molecular approach. Our experiments show a progressive decrease in the power of cognition-relevant hippocampal gamma oscillations during the early stage of amyloid pathology, together with a modification of fast-spiking interneuron intrinsic properties and postsynaptic input. Consistently, transcriptomic analyses revealed that these effects are accompanied by changes in synaptic function-associated pathways. Concurrently, homeostasis-and inflammatory-related microglia signature genes were downregulated. Moreover, we found a decrease in Iba1-positive microglia in the hippocampus that correlates with plaque aggregation and neuronal dysfunction. Collectively, these findings support the hypothesis that microglia play a protective role during the early stages of amyloid pathology by preventing plaque aggregation, supporting neuronal homeostasis, and overall preserving the oscillatory network’s functionality. These results suggest that the early loss of microglia could be a pivotal event in the progression of Alzheimer’s disease, potentially triggering plaque deposition, impairment of fast-spiking interneurons, and the breakdown of the oscillatory circuitry in the hippocampus.

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Section: -Intrinsic Properties Of Fast-spiking Interneuronsmentioning

confidence: 99%