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Pontrello, C.

Publications and source records attributed to Pontrello, C..

3 recordsLinked to original sources

Hypothalamic representation of the imminence of predator threat detected by the vomeronasal organ in mice

Animals have the innate ability to select optimal defensive behaviors with appropriate intensity in response to predator threats within specific contexts. Such innate behavioral decisions are thought to be computed in the medial hypothalamic nuclei, which contain neural populations that directly control defensive behavioral outputs. The vomeronasal organ (VNO) serves as a primary sensory channel for detecting predator cues by relaying signals to the medial hypothalamic nuclei, particularly the ventromedial hypothalamus (VMH), via the medial amygdala (MeA) and bed nucleus of the stria terminalis (BNST). Here, we demonstrate that cat saliva contains predator cues that signal the imminence of predator threat and modulate the intensity of freezing behavior through the VNO in mice. Cat saliva activates neurons expressing the V2R-A4 subfamily of sensory receptors, suggesting that specific receptor groups are responsible for inducing the freezing behavior. The number of VNO neurons activated in response to saliva correlates with both the freshness of saliva and the intensity of freezing behavior. In contrast, the downstream neurons in the accessory olfactory bulb (AOB) and the defensive behavioral circuit are activated to a similar extent by fresh and old saliva. Strikingly, however, the number of VMH neurons activated by fresh, but not old, saliva positively correlates with the intensity of freezing behavior. Detailed analysis of the spatial distribution of neurons responding to fresh and old saliva, as well as the overlap of those activated within the same individual mice, revealed that fresh and old saliva predominantly activate distinct neuronal populations within the VMH. Collectively, this study suggests that there is an accessory olfactory circuit in mice that is specifically tuned to time-sensitive components of cat saliva, which optimizes their defensive behavior to maximize their chance of survival according to the imminence of threat.

neuroscience↗

Plasticity of gene expression in the nervous system by exposure to environmental odorants that inhibit HDACs

Eukaryotes are often exposed to microbes and respond to their secreted metabolites, such as the microbiome in animals or commensal bacteria in roots. Little is known about the effects of long-term exposure to volatile chemicals emitted by microbes, or other volatiles that we are exposed to over a long duration. Using the model system Drosophila melanogaster, we evaluate a yeast emitted volatile, diacetyl, found in high levels around fermenting fruits where they spend long periods of time. We find that exposure to just the headspace containing the volatile molecules can alter gene expression in the antenna. Experiments showed that diacetyl and structurally related volatile compounds inhibited human histone-deacetylases (HDACs), increased histone-H3K9 acetylation in human cells, and caused wide changes in gene expression in both Drosophila and mice. Diacetyl crosses the blood-brain barrier and exposure causes modulation of gene expression in the brain, therefore has potential as a therapeutic. Using two separate disease models known to be responsive to HDAC-inhibitors, we evaluated physiological effects of volatile exposure. First, we find that the HDAC inhibitor also halts proliferation of a neuroblastoma cell line in culture as predicted. Next, exposure to vapors slows progression of neurodegeneration in a Drosophila model for Huntingtons disease. These changes strongly suggest that unbeknown to us, certain volatiles in the surroundings can have profound effects on histone acetylation, gene expression and physiology in animals.

neuroscience↗

Coadaptation of the chemosensory system with voluntary exercise behavior in mice

Ethologically relevant chemical senses and behavioral habits are likely to coadapt in response to selection. As olfaction is involved in intrinsically motivated behaviors in mice, we hypothesized that selective breeding for a voluntary behavior would enable us to identify novel roles of the chemosensory system. Voluntary wheel running (VWR) is an intrinsically motivated and naturally rewarding behavior, and even wild mice run on a wheel placed in nature. We have established 4 independent, artificially evolved mouse lines by selectively breeding individuals showing high VWR activity (High Runners; HRs), together with 4 non-selected Control lines, over 88 generations. We found that several sensory receptors in specific receptor clusters were differentially expressed between the vomeronasal organ (VNO) of HRs and Controls. Moreover, one of those clusters contains multiple single-nucleotide polymorphism loci for which the allele frequencies were significantly divergent between the HR and Control lines, i.e., loci that were affected by the selective breeding protocol. These results indicate that the VNO has become genetically differentiated between HR and Control lines during the selective breeding process, strongly suggesting the chemosensory receptors as quantitative trait loci (QTL) for voluntary exercise in mice. We propose that olfaction may play an important role in motivation for voluntary exercise in mammals.

animal behavior and cognition↗