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Université de Fribourg

Optogenetic stimulation of basal forebrain parvalbumin neurons activates the default mode network and associated behaviors

Lozano-Montes, Laura ; Dimanico, Marta ; Mazloum, Reza ; Li, Wenxue ; Nair, Jayakrishnan ; Kintscher, Michael ; Schneggenburger, Ralf ; Harvey, Michael ; Rainer, Gregor

In: Cell Reports, 2020, vol. 33, no. 6, p. 108359

Activation of the basal forebrain (BF) has been associated with increased attention, arousal, and a heightened cortical representation of the external world. In addition, BF has been implicated in the regulation of the default mode network (DMN) and associated behaviors. Here, we provide causal evidence for a role of BF in DMN regulation, highlighting a prominent role of parvalbumin (PV)...

Université de Fribourg

Gene expression analysis in the mouse brainstem identifies Cart and Nesfatin as neuropeptides coexpressed in the Calbindin-positive neurons of the Nucleus papilio

Girard, Franck ; von Siebenthal, Michelle ; Davis, Fred P. ; Celio, Marco R.

In: Sleep, 2020, vol. 43, no. 2020-11, p. zsaa085

Study Objectives: The brainstem contains several neuronal populations, heterogeneous in terms of neurotransmitter/neuropeptide content, which are important for controlling various aspects of the rapid eye movement (REM) phase of sleep. Among these populations are the Calbindin (Calb)-immunoreactive NPCalb neurons, located in the Nucleus papilio, within the dorsal paragigantocellular nucleus...

Université de Fribourg

Parvalbumin-deficiency accelerates the age-dependent ROS production in Pvalb neurons in vivo: link to neurodevelopmental disorders

Janickova, Lucia ; Schwaller, Beat

In: Frontiers in Cellular Neuroscience, 2020, vol. 14, p. -

In neurodevelopmental disorders (NDDs) including autism spectrum disorder (ASD) and schizophrenia, impairment/malfunctioning of a subpopulation of interneurons expressing the calcium-binding protein parvalbumin (PV) –here termed Pvalb neurons– has gradually emerged as a possible cause. These neurons may represent a hub or point-of-convergence in the etiology of NDD. Increased oxidative...

Université de Fribourg

Absence of parvalbumin increases mitochondria volume and branching of dendrites in inhibitory Pvalb neurons in vivo: a point of convergence of autism spectrum disorder (ASD) risk gene phenotypes

Janickova, Lucia ; Rechberger, Karin Farah ; Wey, Lucas ; Schwaller, Beat

In: Molecular Autism, 2020, vol. 11, no. 1, p. 47

In fast firing, parvalbumin (PV)-expressing (Pvalb) interneurons, PV acts as an intracellular Ca2+ signal modulator with slow-onset kinetics. In Purkinje cells of PV−/− mice, adaptive/homeostatic mechanisms lead to an increase in mitochondria, organelles equally capable of delayed Ca2+ sequestering/buffering. An inverse regulation of PV and mitochondria likewise operates in cell model...

Université de Fribourg

Profiling parvalbumin interneurons using iPSC: challenges and perspectives for Autism Spectrum Disorder (ASD)

Filice, Federica ; Schwaller, Beat ; Michel, Tanja M. ; Grünblatt, Edna

In: Molecular Autism, 2020, vol. 11, no. 1, p. 10

Autism spectrum disorders (ASD) are persistent conditions resulting from disrupted/altered neurodevelopment. ASD multifactorial etiology—and its numerous comorbid conditions—heightens the difficulty in identifying its underlying causes, thus obstructing the development of effective therapies. Increasing evidence from both animal and human studies suggests an altered functioning of the...

Université de Fribourg

Neurons in the Nucleus papilio contribute to the control of eye movements during REM sleep

Gutierrez Herrera, C. ; Girard, Franck ; Bilella, Alessandro ; Gent, T. C. ; Roccaro-Waldmeyer, Diana M. ; Adamantidis, A. ; Celio, Marco R.

In: Nature Communications, 2019, vol. 10, no. 1, p. 1–11

Rapid eye movements (REM) are characteristic of the eponymous phase of sleep, yet the underlying motor commands remain an enigma. Here, we identified a cluster of Calbindin-D28K-expressing neurons in the Nucleus papilio (NPCalb), located in the dorsal paragigantocellular nucleus, which are active during REM sleep and project to the three contralateral eye-muscle nuclei. The firing of...

Università della Svizzera italiana

A bispecific immunotweezer prevents soluble PrP oligomers and abolishes prion toxicity

Bardelli, Marco ; Frontzek, Karl ; Simonelli, Luca ; Hornemann, Simone ; Pedotti, Mattia ; Mazzola, Federica ; Carta, Manfredi ; Eckhardt, Valeria ; D’Antuono, Rocco ; Virgilio, Tommaso ; González, Santiago F. ; Aguzzi, Adriano ; Varani, Luca

In: Plos pathogens, 2018, vol. 14, no. 10, p. e1007335

Antibodies to the prion protein, PrP, represent a promising therapeutic approach against prion diseases but the neurotoxicity of certain anti-PrP antibodies has caused concern. Here we describe scPOM-bi, a bispecific antibody designed to function as a molecular prion tweezer. scPOM-bi combines the complementarity-determining regions of the neurotoxic antibody POM1 and the neuroprotective...

Università della Svizzera italiana

The protein disulfide isomerase ERp57 regulates the steady-state levels of the prion protein

Torres, Mauricio ; Medinas,Danilo B. ; Matamala, José Manuel ; Woehlbier, Ute ; Cornejo, Víctor Hugo ; Solda, Tatiana ; Andreu, Catherine ; Rozas, Pablo ; Matus, Soledad ; Muñoz, Natalia ; Vergara, Carmen ; Cartier, Luis ; Soto, Claudio ; Molinari, Maurizio ; Hetz, Claudio

In: The journal of biological chemistry, 2015, vol. 290, no. 39, p. 23631-23645

Although the accumulation of a misfolded and protease-resistant form of the prion protein (PrP) is a key event in Prion pathogenesis, the cellular factors involved in its folding and quality control are poorly understood. PrP is a glycosylated and disulfide-bonded protein synthesized at the endoplasmic reticulum (ER). The ER foldase ERp57 (also known as Grp58) is highly expressed in the brain...