Assessing Pupil-linked Changes in Locus Coeruleus-mediated Arousal Elicited by Trigeminal Stimulation

Maria Paola Tramonti Fantozzi, Tommaso Banfi, Vincenzo De Cicco, Massimo Barresi, Enrico Cataldo, Davide De Cicco, Luca Bruschini, Paola d'Ascanio, Gastone Ciuti, Ugo Faraguna, Diego Manzoni
JoVE. 2019-11-26; (153):
DOI: 10.3791/59970

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Fantozzi MPT(#)(1), Banfi T(#)(2), De Cicco V(#)(1), Barresi M(3), Cataldo E(4), De Cicco D(1), Bruschini L(5), d’Ascanio P(1), Ciuti G(2), Faraguna U(6), Manzoni D(7).

Author information:
(1)Department of Translational Research and of New Surgical and Medical Technologies, University of Pisa.
(2)The BioRobotics Institute, Scuola Superiore Sant’Anna; Department of Excellence in Robotics & AI, Scuola Superiore Sant’Anna.
(3)Institut des Maladie Neurodegeneratives, University of Bordeaux.
(4)Department of Physics, University of Pisa.
(5)Department of Surgical, Medical, Molecular Pathology and Critical Care Medicine, University of Pisa.
(6)Department of Translational Research and of New Surgical and Medical Technologies, University of Pisa; Department of Developmental Neuroscience, IRCCS Foundation Stella Maris.
(7)Department of Translational Research and of New Surgical and Medical Technologies, University of Pisa; .
(#)Contributed equally

Current scientific literature provides evidence that trigeminal sensorimotor activity associated with chewing may affect arousal, attention, and cognitiveperformance. These effects may be due to widespread connections of the trigeminal system to the ascending reticular activating system (ARAS), to which noradrenergic neurons of the locus coeruleus (LC) belongs. LC neurons contain projections to the whole brain, and it is known that their discharge co-varies with pupil size. LC activation is necessary for eliciting task-related mydriasis. If chewing effects on cognitive performance are mediated by the LC, it is reasonable to expect that changes in cognitive performance are correlated to changes in task-related mydriasis. Two novel protocols are presented here to verify this hypothesis and document that chewing effects are not attributable to aspecific motor activation. In both protocols, performance and pupil size changes observed during specific tasks are recorded before, soon after, and half an hour following a 2 min period of either: a) no activity, b) rhythmic, bilateral handgrip, c) bilateral chewing of soft pellet, and d) bilateral chewing of hard pellet. The first protocol measures level of performance in spotting target numbers displayed within numeric matrices. Since pupil size recordings are recorded by an appropriate pupillometer that impedes vision to ensure constant illumination levels, task-related mydriasis is evaluated during a haptic task. Results from this protocol reveal that 1) chewing-induced changes in performance and task-related mydriasis are correlated and 2) neither performance nor mydriasis are enhanced by handgrip. In the second protocol, use of a wearable pupillometer allows measurement of pupil size changes and performance during the same task, thus allowing even stronger evidence to be obtained regarding LC involvement in the trigeminal effects on cognitive activity. Both protocols have
been run in the historical office of Prof. Giuseppe Moruzzi, the discoverer of ARAS, at the University of Pisa.

DOI: 10.3791/59970
PMID: 31840660

Auteurs Bordeaux Neurocampus