Biology subjects

Liotta, A.

Publications and source records attributed to Liotta, A..

3 recordsLinked to original sources

bioRxiv2026

Syncytial coupling of mid-capillary pericytes underlies seizure-associated electro-metabolic signaling

Disturbances of neurovascular coupling (NVC) contribute to metabolic derailment and neurological symptoms associated with epilepsy. While postictal arterial constriction can be alleviated by inhibitors of voltage gated calcium channels (VGCCs), less is knownregarding seizure-associated electrical signals in higher-order capillaries and their role in determining pericyte tone during seizures. Here we investigated electrical signaling within the ex vivo neurovascular unit (NVU) derived from rat and human brain tissue. We focused on electrical signal transduction between pericytes and endothelial cells and the potential role of VGCCs in vasomotion. Using dye coupling and paired patch-clamp recordings, we showed that morphologically heterogeneous groups of mid-capillary pericytes build a functional syncytium with endothelial cells. Coupling was asymmetric, allowing for directed propagation of electrical signals. Regardless of their morphology, mid-capillary pericytes responded with depolarization and constriction to metabotropic receptor (GPCR) activation (by thromboxane, norepinephrine and UDP-glucose). However, depolarization via the patch pipette induced neithe r Ca2+-influx nor constriction, suggesting lack of contribution of VGCCs to vasomotion. On inducing epileptiform activity, A2a adenosine receptors and inwardly rectifying potassium channels hyperpolarized the capillary syncytium, followed by repeated depolarizations due to seizure-associated potassium increase in the parenchyma. Thus, while mid-capillary pericytes are contractile, their tone does not rely on their membrane potential and VGCCs. However, syncytial coupling allows for transmission of seizure-associated hyper- and depolarizing signals to upstream feeding arterioles.

neuroscience↗

bioRxiv2025

Altered Brain Energy Metabolism in the APPPS1 Alzheimer's Model during anesthesia: Integration of Experimental Data and In Silico Modeling

BackgroundSynaptic transmission and network activity rely on high ATP turnover. Impairments in cerebral energy metabolism are increasingly recognized as central in aging and Alzheimers disease (AD) pathogenesis. Elderly patients and patients with AD are also at elevated risk for perioperative neurological complications, including post-operative delirium and further cognitive deterioration. However, the interaction between metabolic vulnerability and anesthetic exposure remains incompletely understood. MethodsWe investigated cortical metabolic responses and potassium homeostasis in acute brain slices from wild-type (WT) and AD-like APPPS1 transgenic mice, which were either exposed to isoflurane or left untreated. Glia cells were assessed by staining microglia and astrocytes. Measurements of the cerebral metabolic rate of oxygen (CMRO2), extracellular potassium dynamics, and proteomic profiling were integrated with computational modeling to assess oxidative metabolism and anesthetic effects under different conditions. ResultsAPPPS1 mice exhibited reduced CMRO2 and attenuated neuronal activity compared to age-matched WT controls, showing sex-specific differences. Proteomic analysis revealed the downregulation of key mitochondrial and glycolytic enzymes, indicating an impaired ATP- generating capacity. Exposure to isoflurane further suppressed CMRO2, with a more pronounced effect in the APPPS1 brain tissue, while glia cells exhibited no acute changes. Additionally, isoflurane exacerbated deficits in extracellular potassium ([K]) clearance, highlighting impaired ion homeostasis under anesthetic challenge. ConclusionsOur findings demonstrate that AD-like pathology in APPPS1 mice is associated with a significant decline in oxidative metabolism and ATP availability. These deficits are exacerbated by anesthetic exposure, contributing to impaired potassium regulation. This suggests that diminished metabolic flexibility may underlie increased anesthetic vulnerability and postoperative complications in AD.

neuroscience↗

bioRxiv2019

Network-specific synchronization of electrical slow-wave oscillations regulates sleep in Drosophila

Slow-wave rhythms characteristic of deep sleep oscillate in the delta band (0.5-4 Hz) and can be found across various brain regions in vertebrates. Across systems it is however unclear how oscillations arise and whether they are the causal functional unit steering behavior. Here, for the first time in any invertebrate, we discover sleep-relevant delta oscillations in Drosophila. We find that slow-wave oscillations in the sleep-regulating R2 network increase with sleep need. Optical multi-unit voltage recordings reveal that single R2 neurons get synchronized by sensory and circadian input pathways. We show that this synchronization depends on NMDA receptor (NMDARs) coincidence detector function and on an interplay of cholinergic and glutamatergic inputs setting a resonance frequency. Genetically targeting the coincidence detector function of NMDARs in R2, and thus the uncovered mechanism underlying synchronization, abolished network-specific slow-wave oscillations. It also disrupted sleep and facilitated light-induced wakening, directly establishing a causal role for slow-wave oscillations in regulating sleep and sensory gating. We therefore propose that the synchronization-based increase in oscillatory power likely represents an evolutionarily conserved, potentially optimal, strategy for constructing sleep-regulating sensory gates.

neuroscience↗