Biology subjects

Papale, A.

Publications and source records attributed to Papale, A..

2 recordsLinked to original sources

bioRxiv2019

Mouse navigation strategies for odor source localization

Navigating an odor landscape is a critical behavior for the survival of many species, including mice. One ethologically relevant mouse behavior is locating food using odor concentration gradients. To model this behavior, we use a naturalistic open field odor-based spot-finding task, examining navigation strategies as mice search for and approach an odor source. Mice were trained to navigate to odor sources paired with food reward. We detected behavioral changes consistent with localization of the odor source when mice were [~]10cm away from the source. These behaviors included both orientation towards the source and increased exploration time. We found that the amplitude of casting, lateral back and forth head movement, increased exponentially with proximity to the source. We then created concentration-dependent models to simulate mouse behavior, which provided evidence for a serial-sniffing strategy (sampling concentration, moving in space, then sampling again) and a stereo-sniffing strategy (inter-nostril comparison of concentration in a single sniff). Together, these results elucidate key components of behavioral strategies for odor-based navigation. SUMMARY STATEMENTUse of a naturalistic odor-source localizing task uncovers key strategies underlying successful mouse navigation. Concentration-dependent models successfully recapitulate mouse behavior and reveal important behavioral components.

neuroscience↗

bioRxiv2018

Modulation of ERK1/MAPK3 potentiates ERK nuclear signalling, facilitates neuronal cell survival and improves memory in mouse models of neurodegenerative disorders

Cell signalling mechanisms are central to neuronal activity and their dysregulation may lead to neurodegenerative processes and associated cognitive decline. So far, a major effort has been directed toward the dissection of disease specific pathways with the still unmet promise to develop precision medicine strategies. With a different approach, here we show that a selective genetic potentiation of neuronal ERK signalling prevents cell death in vitro and in vivo in the mouse brain while ERK attenuation does the opposite. This neuroprotective effect can also be induced pharmacologically by a cell permeable peptide mimicking the loss of ERK1 MAP kinase, leading to a selective enhancement of ERK2 mediated nuclear cell signalling. The drug treatment prevents neurodegeneration in mouse models of Huntingtons (HD), Alzheimers (AD), and Parkinsons disease (PD). Importantly, the selective potentiation of ERK2 signalling facilitates both structural and synaptic plasticity, enhances cognition in healthy mice and rescues mild cognitive impairments in both models of AD and HD. Altogether, our observation truly represents a remarkable example of a shared molecular mechanism across multiple neurodegenerative disorders and a potentially valuable therapeutic target for neuro-enhancement.

neuroscience↗