Biology subjects

Rizzi, S.

Publications and source records attributed to Rizzi, S..

4 recordsLinked to original sources

bioRxiv2026

Comprehensive classification of HCN1 variants linked to neurodevelopmental disorders with and without epilepsy

Hyperpolarization-activated cyclic nucleotide-gated 1 channels (HCN1) mediate the Ih cationic current and play a central role in regulating neuronal excitability and synaptic integration. HCN1 is predominantly expressed in the neocortex and hippocampus. Pathogenic variants in HCN1 have been increasingly identified in individuals presenting with a broad spectrum of epileptic disorders, ranging from severe developmental and epileptic encephalopathy (DEE) to milder epilepsies. Here, we used patch-clamp electrophysiology in combination with confocal imaging in HEK293 cells to functionally characterize 43 HCN1 variants found in patients presenting with neurodevelopmental disorders, with or without epilepsy. Based on their biophysical properties, we defined four functional classes: (I) low or no current, (II) hyperpolarizing (i.e. left) shift in voltage dependence, (III) depolarizing (i.e. right) shift in voltage dependence, and (IV) generation of an instantaneous current. Integration of this functional classification with detailed clinical data from a cohort of 49 patients revealed a striking genotype-phenotype correlation. Loss-of-function variants were strongly enriched among individuals without epilepsy or with milder generalized phenotypes, whereas gain-of-function and mixed variants were predominantly associated with epilepsy, including all cases of DEE. Notably, non-epileptic cases clustered within a subgroup of loss-of-function variants affecting the selectivity filter. We further show that allosteric modulators, including the peptides NB6 and TRIP8bnano and the small molecule J&J12e, normalize the functional properties of mutant HCN1 channels in three classes. These findings establish a clinically relevant framework for interpreting HCN1 gain- and loss-of-function variants suggesting that the direction of channel dysfunction is a major determinant of epilepsy risk and severity.

pathology↗

bioRxiv2022

Migration strategy varies with novel environment response in common noctule bats

Global ecosystems are changing dramatically due to land transformation and climate change. Global change is a particular challenge for migratory animals that rely on multiple stepping stones on their journeys. Migratory animals have a range of strategies to accomplish this, but not all of these strategies may be appropriate for the challenges ahead. Understanding the variation in migratory strategies and their behavioural correlates is therefore critical to understand how vulnerable species will be in the future, especially in endangered and elusive taxa such as bats. Here, we combined isotopic geolocation with an in-situ behavioural assay to investigate whether behavioural responses to a roost-like novel environment correlated with variation in migration strategies (local or distant origin based on isotopic geographic assignments), in the partially migratory bat, Nyctalus noctula. We quantified emergence behaviour, spatial activity, and echolocation call activity. Local bats were more likely to emerge into the novel environment than bats from more distant origins. However, local and distant bats did not differ in spatial activity and acoustic exploration (relative call activity per space unit). Our findings indicate that local bats may more pro-actively cope with novelty, but that acoustic exploration is equally important for local and migratory bats during explorations.

animal behavior and cognition↗

bioRxiv2020

In situ novel environment assay reveals acoustic exploration as a repeatable behavioral response in migratory bats

Integrating information on species-specific sensory perception together with spatial activity provides a high-resolution understanding of how animals explore environments, yet frequently used exploration assays commonly ignore sensory acquisition as a measure for exploration. Echolocation is an active sensing system used by hundreds of mammal species, primarily bats. As echolocation call activity can be reliably quantified, bats present an excellent animal model to investigate intra-specific variation in environmental cue sampling. Here, we developed an in situ roost-like novel environment assay for tree-cave roosting bats. We repeatedly tested 52 individuals of the migratory bat species, Pipistrellus nathusii, across 24 hours, to examine the role of echolocation when crawling through a maze-type arena and test for consistent intra-specific variation in sensory-based exploration. We reveal a strong correlation between echolocation call activity and spatial activity. Moreover, we show that during the exploration of the maze, individuals consistently differed in spatial activity as well as echolocation call activity given their spatial activity, a behavioral response we term acoustic exploration. Acoustic exploration was correlated with other exploratory behaviors, but not with emergence latency. We here present a relevant new measure for exploration behavior and provide evidence for consistent (short-term) intra-specific variation in the level at which wild bats collect information from a novel environment.

animal behavior and cognition↗

bioRxiv2020

Causal evidence for the adaptive benefits of social foraging in the wild

Sociality is a fundamental organizing principle across taxa, thought to come with a suite of adaptive benefits. However, making causal inferences about these adaptive benefits requires experimental manipulation of the social environment, which is rarely feasible in the field. Here we manipulated the number of conspecifics in Trinidadian guppies (Poecilia reticulata) in the wild, and quantified how this affected a key benefit of sociality, social foraging, by investigating several components of foraging success. As adaptive benefits of social foraging may differ between sexes, we studied males and females separately, expecting females, the more social and risk-averse sex, to benefit more from conspecifics than males. Conducting over 1,600 foraging trials, we found that in both sexes, increasing the number of conspecifics led to faster detection of novel food patches and a higher probability of feeding following detection of the patch, resulting in greater individual resource consumption. The slope of the latter relationship differed between the sexes, with males unexpectedly exhibiting a stronger social benefit. Our study provides rare causal evidence for the adaptive benefits of social foraging in the wild, and highlights that sex differences in sociality do not necessarily imply an unequal ability to profit from the presence of others.

animal behavior and cognition↗