Publications by authors named "Pinelopi Pliota"

5 Publications

  • Page 1 of 1

Ubiquitous Selfish Toxin-Antidote Elements in Caenorhabditis Species.

Curr Biol 2021 Jan 4. Epub 2021 Jan 4.

Department of Human Genetics, Department of Biological Chemistry, and Howard Hughes Medical Institute, University of California, Los Angeles, Los Angeles, CA 90095, USA; Department of Biological Chemistry, University of California, Los Angeles, Los Angeles, CA 90095, USA. Electronic address:

Toxin-antidote elements (TAs) are selfish genetic dyads that spread in populations by selectively killing non-carriers. TAs are common in prokaryotes, but very few examples are known in animals. Here, we report the discovery of maternal-effect TAs in both C. tropicalis and C. briggsae, two distant relatives of C. elegans. In C. tropicalis, multiple TAs combine to cause a striking degree of intraspecific incompatibility: five elements reduce the fitness of >70% of the F hybrid progeny of two Caribbean isolates. We identified the genes underlying one of the novel TAs, slow-1/grow-1, and found that its toxin, slow-1, is homologous to nuclear hormone receptors. Remarkably, although previously known TAs act during embryonic development, maternal loading of slow-1 in oocytes specifically slows down larval development, delaying the onset of reproduction by several days. Finally, we found that balancing selection acting on linked, conflicting TAs hampers their ability to spread in populations, leading to more stable genetic incompatibilities. Our findings indicate that TAs are widespread in Caenorhabditis species and target a wide range of developmental processes and that antagonism between them may cause lasting incompatibilities in natural populations. We expect that similar phenomena exist in other animal species.
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http://dx.doi.org/10.1016/j.cub.2020.12.013DOI Listing
January 2021

Central amygdala circuit dynamics underlying the benzodiazepine anxiolytic effect.

Mol Psychiatry 2021 02 30;26(2):534-544. Epub 2018 Nov 30.

Research Institute of Molecular Pathology (IMP), Vienna Biocenter (VBC), Campus-Vienna-Biocenter 1, 1030, Vienna, Austria.

Benzodiazepines (BZDs) have been a standard treatment for anxiety disorders for decades, but the neuronal circuit interactions mediating their anxiolytic effect remain largely unknown. Here, we find that systemic BZDs modulate central amygdala (CEA) microcircuit activity to gate amygdala output. Combining connectome data with immediate early gene (IEG) activation maps, we identified the CEA as a primary site for diazepam (DZP) anxiolytic action. Deep brain calcium imaging revealed that brain-wide DZP interactions shifted neuronal activity in CEA microcircuits. Chemogenetic silencing showed that PKCδ/SST neurons in the lateral CEA (CEAl) are necessary and sufficient to induce the DZP anxiolytic effect. We propose that BZDs block the relay of aversive signals through the CEA, in part by local binding to CEAl SST/PKCδ neurons and reshaping intra-CEA circuit dynamics. This work delineates a strategy to identify biomedically relevant circuit interactions of clinical drugs and highlights the critical role for CEA circuitry in the pathophysiology of anxiety.
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http://dx.doi.org/10.1038/s41380-018-0310-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6411154PMC
February 2021

Dorsal tegmental dopamine neurons gate associative learning of fear.

Nat Neurosci 2018 07 27;21(7):952-962. Epub 2018 Jun 27.

Research Institute of Molecular Pathology (IMP), Vienna Biocenter (VBC), Vienna, Austria.

Functional neuroanatomy of Pavlovian fear has identified neuronal circuits and synapses associating conditioned stimuli with aversive events. Hebbian plasticity within these networks requires additional reinforcement to store particularly salient experiences into long-term memory. Here we have identified a circuit that reciprocally connects the ventral periaqueductal gray and dorsal raphe region with the central amygdala and that gates fear learning. We found that ventral periaqueductal gray and dorsal raphe dopaminergic (vPdRD) neurons encode a positive prediction error in response to unpredicted shocks and may reshape intra-amygdala connectivity via a dopamine-dependent form of long-term potentiation. Negative feedback from the central amygdala to vPdRD neurons might limit reinforcement to events that have not been predicted. These findings add a new module to the midbrain dopaminergic circuit architecture underlying associative reinforcement learning and identify vPdRD neurons as a critical component of Pavlovian fear conditioning. We propose that dysregulation of vPdRD neuronal activity may contribute to fear-related psychiatric disorders.
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http://dx.doi.org/10.1038/s41593-018-0174-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6166775PMC
July 2018

Stress peptides sensitize fear circuitry to promote passive coping.

Mol Psychiatry 2020 02 14;25(2):428-441. Epub 2018 Jun 14.

Research Institute of Molecular Pathology (IMP), Vienna Biocenter (VBC), Dr. Bohr Gasse 7, 1030, Vienna, Austria.

Survival relies on optimizing behavioral responses through experience. Animals often react to acute stress by switching to passive behavioral responses when coping with environmental challenge. Despite recent advances in dissecting mammalian circuitry for Pavlovian fear, the neuronal basis underlying this form of non-Pavlovian anxiety-related behavioral plasticity remains poorly understood. Here, we report that aversive experience recruits the posterior paraventricular thalamus (PVT) and corticotropin-releasing hormone (CRH) and sensitizes a Pavlovian fear circuit to promote passive responding. Site-specific lesions and optogenetic manipulations reveal that PVT-to-central amygdala (CE) projections activate anxiogenic neuronal populations in the CE that release local CRH in response to acute stress. CRH potentiates basolateral (BLA)-CE connectivity and antagonizes inhibitory gating of CE output, a mechanism linked to Pavlovian fear, to facilitate the switch from active to passive behavior. Thus, PVT-amygdala fear circuitry uses inhibitory gating in the CE as a shared dynamic motif, but relies on different cellular mechanisms (postsynaptic long-term potentiation vs. presynaptic facilitation), to multiplex active/passive response bias in Pavlovian and non-Pavlovian behavioral plasticity. These results establish a framework promoting stress-induced passive responding, which might contribute to passive emotional coping seen in human fear- and anxiety-related disorders.
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http://dx.doi.org/10.1038/s41380-018-0089-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6169733PMC
February 2020

Transgenic mouse models enabling photolabeling of individual neurons in vivo.

PLoS One 2013 23;8(4):e62132. Epub 2013 Apr 23.

Research Institute of Molecular Pathology (IMP), Vienna, Austria.

One of the biggest tasks in neuroscience is to explain activity patterns of individual neurons during behavior by their cellular characteristics and their connectivity within the neuronal network. To greatly facilitate linking in vivo experiments with a more detailed molecular or physiological analysis in vitro, we have generated and characterized genetically modified mice expressing photoactivatable GFP (PA-GFP) that allow conditional photolabeling of individual neurons. Repeated photolabeling at the soma reveals basic morphological features due to diffusion of activated PA-GFP into the dendrites. Neurons photolabeled in vivo can be re-identified in acute brain slices and targeted for electrophysiological recordings. We demonstrate the advantages of PA-GFP expressing mice by the correlation of in vivo firing rates of individual neurons with their expression levels of the immediate early gene c-fos. Generally, the mouse models described in this study enable the combination of various analytical approaches to characterize living cells, also beyond the neurosciences.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0062132PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3633923PMC
November 2013