Biology subjects

Volterra, A.

Publications and source records attributed to Volterra, A..

2 recordsLinked to original sources

bioRxiv2026

Deletion of TNFR1 in astrocytes restores memory in aged Alzheimer's disease mice

Astrocytes participate in local inflammation and cognitive decline in Alzheimers disease (AD). Aberrant cytokine TNF signaling via astrocyte type-1 receptor (aTNFR1) could causally link the two AD pathology aspects. To verify this hypothesis, we crossed transgenic AD mice with mice enabling astrocyte-specific conditional TNFR1 deletion (aTNFR1KO). Induction of aTNFR1KO at early AD stages, preserved memory and reduced {beta}-amyloid load and astrogliosis in the aged mice. Induction of aTNFR1KO at late AD stages, in mice already memory-impaired, surprisingly produced rapid memory rescue, without affecting {beta}-amyloid load and astrogliosis. Single nucleus-RNA-seq analysis of all hippocampal cell populations revealed that late-stage aTNFR1KO rapidly modifies gene expression mainly in neurons, primarily targeting synaptic pathways, causing combined glutamatergic downregulation and GABAergic up-regulation. Consistently, hippocampal EEGs showed a pro-inhibitory effect of aTNFR1KO, which thus restores memory by "rebalancing" hippocampal circuitry excitability. This pro-memory effect identifies a new mechanism and astrocyte target against cognitive decline in AD.

neuroscience↗

bioRxiv2024

Fast 3D imaging in the auditory cortex of awake mice reveals that astrocytes control neurovascular coupling responses locally at arteriole-capillary junctions.

Neurovascular coupling (NVC) increases blood flow, assuring adequate supply to active cortical regions by local redistribution via penetrating arterioles (PA) and branching capillaries. Astrocyte end-feet enwrapping these vascular structures possess machinery to regulate blood flow, but their participation in NVC is controversial. Via a new 3D+t two-photon imaging approach we visualized PA and capillaries simultaneously during naturally-occurring and tone-evoked dilations in the auditory cortex of awake mice. We observed that dilations occurred bidirectionally, and a fraction of them extended between compartments across the interconnecting sphincter, depending on the animal activity states. These multi-compartment dilations were preceded by rapid astrocyte end-foot Ca2+ signals around the sphincter. Reduction of this astrocytic Ca2+ activity in IP3R2KO mice suppressed multi-compartment dilations, revealing a pivotal role of pre-capillary sphincters in their bidirectional spread between vascular compartments under local control by astrocytes. This novel mechanism contributes to physiological regulation of laminar blood flow during NVC.

neuroscience↗