Biology subjects

Signoret-Genest, J.

Publications and source records attributed to Signoret-Genest, J..

3 recordsLinked to original sources

bioRxiv2026

Deep brain stimulation of the mesencephalic locomotor centre induces stimulation-dependent behavioural states beyond locomotion

Deep brain stimulation (DBS) of the mesencephalic locomotor region (MLR) has been explored to treat gait disturbances. However, clinical outcomes of MLR-DBS have been disappointing overall, with only modest benefits in some individuals and unwanted effects, including anxiety, reported in others. Preclinical studies in several species, by contrast, show that MLR-DBS can improve locomotor and gait deficits, although defensive behaviours in response to stimulation have also been reported in some species. To investigate this discrepancy, we examined frequency- and amplitude-dependent effects of MLR-DBS in healthy rats, combining semi-supervised and unsupervised behavioural analyses. High-frequency, high-amplitude DBS (80-130 Hz), but not low-frequency stimulation (20-60 Hz), elicited hyperlocomotion intermixed with acute defensive-like behaviours. Low-frequency stimulation instead promoted phases of immobility. Consistently, only high-frequency DBS induced region-specific c-Fos expression in the MLR. Complex behaviours, including hyperlocomotion, rearing, tail rattling, and periods of immobility, were most pronounced in animals with the DBS electrode tip localized to the cuneiform nucleus (CnF) of the MLR. Using AAV tracer constructs for bright labelling of CaMKII-positive neurons and their axons, we identified prominent ascending projections from the CnF to the thalamus, substantia nigra pars compacta, zona incerta, hypothalamus, subthalamic nucleus, and central amygdala (CeA). Retrograde tracing confirmed the CnF-to-CeA projection independently. These findings show that the MLR is anatomically connected to higher-order centres linking motor and defensive networks, with DBS frequency and amplitude critically shaping behavioural outcomes that extend beyond locomotion.

neuroscience↗

bioRxiv2023

A viral vector model for circuit-specific synucleinopathy

In Parkinsons disease (PD), pathomechanisms such as aberrant network dysfunctions can be elucidated by conducting multiscale explorations in animal models. However, the lack of specificity in the existing models limits a restricted targeting of individual network elements and characterization of PD as a "circuitopathy". We therefore developed a cell-type specific viral vector (AAV2/9-CreON-A53T-Syn) mouse model that allows to induce synucleinopathy within individual circuit elements in vivo. When specifically targeted to dopaminergic (DA) neurons of the substantia nigra pars compacta (SNc), our approach recapitulates the main hallmarks of the disease, namely Lewy-body-like aggregation, progressive cellular and nigrostriatal projections loss, together with locomotor impairment. Our strategy is supported by new state-of-the-art analytical approaches for cell quantification and behavior characterization. Altogether, we provide a novel model of synucleinopathy, which offers new opportunities to study the contribution of individual network elements to disease pathomechanisms.

neuroscience↗

bioRxiv2022

Integrated cardio-behavioural defensive states

Fear and anxiety are brain states that evolved to mediate defensive responses to threat. While it is clear that the defense reaction includes multiple interacting behavioural, autonomic and endocrine adjustments, their integrative nature is poorly understood. In particular, threat has been associated with various cardiac changes, yet a clear consensus on their relevance for the integrated defense reaction is missing. We here define rapid microstates associated with specific behaviours and heart rate dynamics, both affected by long-lasting macrostates and reflecting context-dependent threat levels. In addition, we demonstrate that one of the most commonly used defensive behavioural responses, freezing measured by immobility, is part of an integrated cardio-behavioural microstate mediated by specific midbrain circuit elements. Our work puts forth a framework for systematic integration of cardiac and behavioural readouts that presents the basis for a better understanding of complex neural defensive states and their associated systemic functions.

neuroscience↗