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Paradiso, E.

Publications and source records attributed to Paradiso, E..

3 recordsLinked to original sources

Investigating the mechanistic role of painful self-experience in emotional contagion: an effect of auto-conditioning?

Emotional contagion refers to the transmission of emotions from one conspecific to another. Previous research in rodents has demonstrated that the self-experience of footshocks enhances how much an observer is affected by the emotional state of a conspecific in pain or distress. We hypothesized auditory auto-conditioning to contribute to this enhancement: during the observers own experience of shocks, the animal associates its own audible nocifensive responses, i.e. its pain squeaks, with the negative affective state induced by the shock. When the animal later witnesses a cage mate receive shocks and hears it squeak, the previously strengthened connection between fear and squeaks could be a mechanism eliciting the enhanced fearful response in the observer. As hypothesized, in a first study, we found pre-exposure to shocks to increase freezing and 22 kHz vocalizations associated with distress upon the playback of pain squeaks. Freezing was also increased during the playbacks of phase-scrambled squeaks, but 22 kHz calls were more frequent during the playback of regular squeaks. Core to the notion of auto-conditioning is that the effect of pre-exposure is due to the pairing of a pain-state with hearing ones own pain squeaks. In a second study, we therefore compared the response to squeak playbacks after animals had been pre-exposed to pairings of a CO2 laser with a squeak playback against three control groups that were pre-exposed to the CO2 laser alone, to squeak playbacks alone or to neither of these conditions. We however could not find any differences in freezing or 22 kHz calls among all experimental groups. In summary, we demonstrate the sufficiency of pain squeaks to trigger fear in a way that critically depends on the nature of an animals prior experience and discuss why the pairing of a CO2 laser with pain squeaks cannot substitute footshock pre-exposure.

animal behavior and cognition↗

Membrane estrogen receptor (GPER) and follicle-stimulating hormone receptor heteromeric complexes promote human ovarian follicle survival

Classically, follicle stimulating hormone receptor (FSHR) driven cAMP-mediated signaling boosts human ovarian follicle growth and would be essential for oocyte maturation. However, contradicting in vitro suggest a different view on physiological and clinical significance of FSHR-mediated cAMP signaling. We found that the G protein coupled estrogen receptor (GPER) heteromerizes with FSHR, reprogramming cAMP/death signals into proliferative stimuli fundamental for sustaining oocyte survival. In human granulosa cells, survival signals are effectively delivered upon equal expression levels of both receptors, while they are missing at high FSHR:GPER ratio, which negatively impacts follicle maturation and strongly correlates with FSH responsiveness of patients undergoing controlled ovarian stimulation. Consistent with high FSHR expression levels during follicular selection, cell viability is dramatically reduced in FSHR overexpressing cells due to preferential coupling to the Gs protein/cAMP pathway. In contrast, FSHR/GPER heteromer formation resulted in FSH-triggered anti-apoptotic/proliferative signaling delivered via the G{beta}{gamma} dimer while heteromer impairment or GPER-associated Gs inhibitory protein complexes resulted in cell death. GPER-depleted granulosa cells have an amplified FSH-dependent decrease in cell viability and steroidogenesis, consistent with the requirement of estrogen signaling for successful oocyte growth. Therefore, our findings indicate how oocyte maturation depends on the capability of GPER to shape FSHR selective signals, indicating hormone receptor heteromers may be a marker of cell proliferation. One Sentence SummaryFSHR/GPER heteromers block cAMP-dependent selection of ovarian follicles and target tumor growth and poor FSH-response in women.

physiology↗

Adaptive disinhibitory gating by VIP interneurons permits associative learning

Learning drives behavioral adaptations necessary for survival. While plasticity of excitatory projection neurons during associative learning is studied extensively, little is known about the contributions of local interneurons. Using fear conditioning as a model for associative learning, we find that behaviorally relevant, salient stimuli cause learning by tapping into a local microcircuit consisting of precisely connected subtypes of inhibitory interneurons. By employing calcium imaging and optogenetics, we demonstrate that vasoactive intestinal peptide (VIP)-expressing interneurons in the basolateral amygdala are activated by aversive events and provide an instructive disinhibitory signal for associative learning. Notably, VIP interneuron responses are plastic and shift from the instructive to the predictive cue upon memory formation. We describe a novel form of adaptive disinhibitory gating by VIP interneurons that allows to discriminate unexpected, important from irrelevant information, and might be a general dynamic circuit motif to trigger stimulus-specific learning, thereby ensuring appropriate behavioral adaptations to salient events.

neuroscience↗