Biology subjects

Fiorillo, C.

Publications and source records attributed to Fiorillo, C..

2 recordsLinked to original sources

bioRxiv2026

Striatal Cholinergic Interneurons Signal Aversion and Drive Avoidance

Seeking reward and avoiding punishment are essential for survival. However, how the brain learns aversive value and generates avoidance remains poorly understood. We investigate acetylcholine-releasing striatal cholinergic interneurons (ChIs), which exhibit prominent excitation to salient behavioral cues but have largely been postulated to play a permissive role in reinforcement learning. Using voltage imaging in mice performing aversive versus reward conditioning tasks, we reveal learning-mediated changes in both subthreshold membrane voltage and suprathreshold spiking of individual ChIs. Across tasks, ChIs exhibit stronger immediate excitation to conditioned cues predicting negative outcomes than positive outcomes. This valence-dependent response augmentation reflects a learning-induced network change specific to cues predicting negative outcomes. Furthermore, brief optogenetic silencing of this immediate excitation selectively impairs conditioned avoidance, but not conditioned approach. Together, these results reveal that ChIs actively signal evidence for aversion and play a critical role in driving avoidance, highlighting a cholinergic mechanism underlying aversive learning.

neuroscience↗

bioRxiv2019

Impairments in contractility and cytoskeletal organisation cause nuclear defects in nemaline myopathy

Nemaline myopathy (NM) is a genetically heterogeneous skeletal muscle disorder caused by mutations predominately affecting contractile filaments, in particular thin filament structure and/or regulation. The underlying cellular pathophysiology of this disease remains largely unclear. Here, we report novel pathological defects in skeletal muscle fibres of mice and patients with NM, including disrupted nuclear envelope, altered chromatin arrangement, and disorganisation of the cortical cytoskeleton. We demonstrate that such nuclear defects are caused by impairment of muscle fibre contractility, and that cytoskeletal organisation determines nuclear morphology. Our results overlap with findings in diseases caused by mutations in nuclear envelope or cytoskeletal proteins. Given the important role of nuclear shape and envelope in regulating gene expression, and the cytoskeleton in maintaining muscle fibre integrity, our findings are likely to underlie some of the hallmarks of NM, which include broad transcriptional alterations, arrested muscle fibre growth, contractile filament disarray and altered mechanical properties.

cell biology↗