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Pallesi, E.

Publications and source records attributed to Pallesi, E..

2 recordsLinked to original sources
bioRxiv2025

Early and transient increase in cortical pyramidal cell excitability and delayed alteration of evoked synaptic transmission and t-SNARE proteins content in the hippocampus and neocortex of neonatal and juvenile STXBP1 heterozygous mice

De novo mutations in the STXBP1 gene leads to the haploinsufficiency of Munc18.1 protein in patient, and represent one of the major causes of neurodevelopmental disorders including developmental epileptic and non-epileptic encephalopathies. Given the fundamental role of this protein in vesicular exocytosis, most electrophysiological studies have focused on the impact of this haploinsufficiency on synaptic transmission, and much less on intrinsic neuronal properties. Furthermore, the possibility that the electrophysiological consequences may be dependent on the developmental stage has not yet been investigated. Here, we analyze using acute brain slices from neonatal and juvenile STXBP1 heterozygous mice the intrinsic properties as well as spontaneous and evoked glutamatergic and GABAergic synaptic transmission in pyramidal cells located in the CA1 region of the hippocampus and in layers II/III of the motor cortex. We show that Munc18.1 deficiency has different electrophysiological consequences in neonatal (postnatal days, PND 4-7) and juvenile mice (PND30-35). The deficit of Munc18.1 leads to an increase in the intrinsic excitability of hippocampal and motor cortical pyramidal cells in neonates while in juveniles, it is evoked synaptic transmission that is affected, with a greater sensitivity of glutamatergic synapses than of GABAergic synapses in response to high-frequency electrical stimulation. However spontaneous ongoing synaptic activity mediated by glutamate and GABA receptors was unaffected at both stages of development. In addition, we performed western blot analysis and observed that Munc18.1 deficiency in STXBP1 heterozygous mice is associated with decreased t-SNARE proteins expression levels in the hippocampus and neocortex of juvenile but not neonatal mice. Therefore, Munc18.1 deficiency has multiple electrophysiological and biochemical consequences, which depend on the developmental stage. These data suggest also that an alteration in the function of some ion channels is one of the first electrophysiological consequences of the deficit of Munc18.1 and we suggest that the decrease in t-SNARE proteins expression could contribute to the normalization of pyramidal cells firing properties in juvenile.

neuroscience↗
bioRxiv2025

Inhibition of oxytocin neurons during key periods of development has long-term behavioural and body composition effects

BackgroundOxytocin (OT) is a key neuromodulator of social behavior in mammals, and accumulating evidence supports the existence of a critical period for OT action during infancy. However, other developmental windows remain poorly explored, and it remains unclear whether OT exert distinct functions depending on the timing of its activity. In this study, we aimed to determine whether specific developmental stages exist during which OT-expressing neurons play a decisive role with long-term consequences. MethodsWe used a chemogenetic approach to transiently inhibit OT-expressing neurons during three postnatal developmental periods: infancy, the juvenile period, and young adulthood in male and female mice. Behavioral and metabolic outcomes were then assessed longitudinally. We also examined the effects of inhibiting OT neurons during late fetal stages and at birth. ResultsSocial memory was consistently impaired in males, regardless of the timing of neuronal inactivation. The most pronounced behavioral effects were observed following inhibition during infancy in both sexes. Metabolically, adult males from all cohorts exhibited increased body weight, whereas increased fat mass and adipocyte size hypertrophy were specifically observed following inhibition during the juvenile period. Notably, inhibition of OT-expressing neurons around the time of birth resulted in delayed parturition and altered neonatal feeding behavior. LimitationsOT-expressing neurons release multiple signaling molecules. However, converging evidence suggests that the observed phenotypes are primarily attributable to OT deficiency. Although this study demonstrates long-term behavioral and metabolic consequences of transient OT neuron inhibition, further experiments are required to elucidate underlying mechanisms and identify additional effects. ConclusionsTransient inhibition of OT-expressing neurons during distinct postnatal developmental periods leads to long-lasting effects on social behavior and metabolism, with outcomes depending on both the timing of inhibition and sex. Furthermore, our findings reveal an unexpected role for fetal/neonatal OT neurons in regulating the timing of birth and early feeding behavior.

neuroscience↗