Quentin Montardy

Off-grid low-tech living is increasingly proposed for arid environments, yet longitudinal field data documenting health, nutrition, and rest–activity organization under real-world conditions remain scarce. Our objective was to describe physiologic, nutritional, psychological, and rest-activity trajectories during 120 d of low-tech off-grid desert living. This was a prospective observational case study of 2 participants (female, 29 y old; male, 39 y old) conducted in Baja California (January–April 2023). Pre-, mid-, and post-mission assessments included bioimpedance body composition, incremental cycle ergometry with gas exchange (VO _{2 max} and ventilatory thresholds), and laboratory panels (eg, hematology, iron status, vitamins, trace elements, and renal and hepatic indices). Mental health was assessed using the State-Trait Anxiety Inventory, the Positive and Negative Affect Schedule, and daily mood ratings. Continuous wrist actigraphy quantified sleep-wake timing and nonparametric rest-activity metrics. Analyses were descriptive and within participant. Body mass decreased by ∼2 kg in both participants, primarily through reduced fat mass with preserved lean indices. VO _{2 max} increased over time without evidence of physiologic compromise. No biochemical marker of micronutrient deficiency was identified. Although locally produced foods contributed ∼1% of total energy intake, they provided substantial micronutrient density. Ferritin levels remained within reference intervals despite transient mid-mission fluctuation in the female participant. Rest-activity rhythms remained robust across 120 d, with seasonal adjustment of sleep timing and modest sleep reduction. Anxiety did not increase, and affect balance remained positive. In this descriptive field case, prolonged low-tech off-grid desert living was compatible with maintenance of physical and psychological health. These findings provide ecologically grounded observations relevant to human functioning in resource-limited environments.

Dopamine (DA) system is intriguing in the aspect that distinct, typically opposing physiological functions are mediated by D1 dopamine receptors (Drd1) and D2 dopamine receptors (Drd2). Both Drd1+ and Drd2+ neurons were identified in superior colliculus (SC), a visuomotor integration center known for its role in defensive behaviors to visual threats. We hypothesized that Drd1+ and Drd2+ neurons in the SC may play a role in promoting instinctive defensive responses. Optogenetic activation of Drd2+ neurons, but not Drd1+ neurons, in the SC triggered strong defensive behaviors. Chemogenetic inhibition of SC Drd2+ neurons decreased looming-induced defensive behavior, suggesting involvement of SC Drd2+ neurons in defensive responses. To further confirm this functional role of Drd2 receptors, pretreatment with the Drd2+ agonist quinpirole in the SC impaired looming-evoked defensive responses, suggesting an essential role of Drd2 receptors in the regulation of innate defensive behavior. Inputs and outputs of SC Drd2+ neurons were investigated using viral tracing: SC Drd2+ neurons mainly receive moderate inputs from the Locus Coeruleus (LC), whilst we did not find any incoming projections from other dopaminergic structures. Our results suggest a sophisticated regulatory role of DA and its receptor system in innate defensive behavior.

In rodents, innate and learned fear of predators depends on the medial hypothalamic defensive system, a conserved brain network that lies downstream of the amygdala and promotes avoidance via projections to the periaqueductal gray. Whether this network is involved in primate fear remains unknown. To address this, we provoked flight responses to a predator (moving snake) in the marmoset monkey under laboratory conditions. We combined c-Fos immunolabeling and anterograde/retrograde tracing to map the functional connectivity of the ventromedial hypothalamus, a core node in the medial hypothalamic defensive system. Our findings demonstrate that the ventromedial hypothalamus is recruited by predator exposure in primates and that anatomical connectivity of the rodent and primate medial hypothalamic defensive system are highly conserved.

Glutamatergic and GABAergic neurons represent the neural components of the medial vestibular nuclei. We assessed the functional role of glutamatergic and GABAergic neuronal pathways arising from the vestibular nuclei (VN) in the maintenance of gait and balance by optogenetically stimulating the VN in VGluT2-cre and GAD2-cre mice. We demonstrate that glutamatergic, but not GABAergic VN neuronal subpopulation is responsible for immediate and strong posturo-locomotor deficits, comparable to unilateral vestibular deafferentation models. During optogenetic stimulation, the support surface dramatically increased in VN ^VGluT2+ mice, and rapidly fell back to baseline after stimulation, whilst it remained unchanged during similar stimulation of VN ^GAD2+ mice. This effect persisted when vestibular compensation was removed. Posturo-locomotor alterations evoked in VN ^VGluT2+ animals were still present immediately after stimulation, while they disappeared 1h later. Overall, these results indicate a fundamental role for VN ^VGluT2+ neurons in balance and posturo-locomotor functions, but not for VN ^GAD2+ neurons, in this specific context. This new optogenetic approach will be useful to characterize the role of the different VN neuronal populations involved in vestibular physiology and pathophysiology. Highlights: For the first time, Vestibular nuclei were optogenetically stimulated in free-moving animals, to asses for glutamatergic and GABAergic neurons functions in posturo-locomotor behaviors. Brief optogenetic activation of VNVGluT2+, but not VNGAD2+, induced immediate and strong postural deficit. Stimulation of VNVGluT2+ neurons provoked an imbalance with continuous effect on locomotion for a short period of time after stimulation. These results are comparable to the classical vestibular deafferentation models during their peak of deficit, and set optogenetic stimulation as a new model to study vestibular deficits.

In rodents, innate and learned fear of predators depends on the medial hypothalamic defensive system, a conserved brain network that lies downstream of the amygdala. However, it remains unknown whether this network is involved in primate fear. Here we demonstrate that visually evoked predator fear recruits a homologous medial hypothalamic defense system in the nonhuman primate

It is though that only a subset of brain structures can encode emotional states. This can be investigated though a set of properties, including the ability of neurons to respond to a conditioned stimulus (CS) preceding an aversive unconditioned stimulus (US). The dorsolateral periacqueductal gray (dPAG) is a midbrain structure though to have an essential role in coordinating defensive behaviors in response to aversive stimulation. But its ability of dPAG neurons to encode a CS following fear conditioning as not been sufficiently studied. Here we used calcium imaging by fiber photometry to record the activity of dPAG ^VGluT2+ and dPAG ^GAD2+ neuronal populations during unconditioned and conditioned aversive stimulation. Then, following an unconditioned stimulation we performed a retrieval experiment to quantify memory-like responses of dPAG neurons. This shown that whilst both dPAG ^VGluT2+ and dPAG ^GAD2+ neuronal populations respond to direct US stimulation, and to CS stimulation during conditioning, only the dPAG ^VGluT2+ population persisted in responding to the CS stimulation during retrieval. Finally, to better understand dPAG ^VGluT2+ and dPAG ^GAD2+ connectivity patterns, we performed a cell specific monosynaptic retrograde rabies virus tracing experiment. This revealed that different patterns of fibers projects to dPAG ^VGluT2+ and dPAG ^GAD2+ , further complementing our recording showing divergences between PAG ^VGluT2+ and dPAG ^GAD2+ populations.

SUMMARY: Innate defensive responses are essential for animal survival and are conserved across species. The ventral tegmental area (VTA) plays important roles in learned appetitive and aversive behaviors, but whether it plays a role in mediating or modulating innate defensive responses is currently unknown. We report that GABAergic neurons in the mouse VTA (VTA ^GABA+ ) are preferentially activated compared to VTA dopaminergic (VTA ^DA+ ) neurons when a threatening visual stimulus evokes innate defensive behavior. Functional manipulation of these neurons showed that activation of VTA ^GABA+ neurons is indispensable for looming-evoked defensive flight behavior and photoactivation of these neurons is sufficient for looming-evoked defensive-like flight behavior, whereas no such role can be attributed for VTA ^DA+ neurons. Viral tracing and in vivo and in vitro electrophysiological recordings showed that VTA ^GABA+ neurons receive direct excitatory inputs from the superior colliculus (SC). Furthermore, we showed that glutamatergic SC-VTA projections synapse onto VTA ^GABA+ neurons that project to the central nucleus of the amygdala (CeA) and that the CeA is involved in mediating the defensive behavior. Our findings demonstrate that visual information about aerial threats access to the VTA ^GABA+ neurons mediating innate behavioral responses, suggesting a more general role for the VTA.

The Ventral Tegmental Area (VTA) is a midbrain structure known to integrate aversive and rewarding stimuli, a function involving VTA Dopaminergic and GABAergic neurons. VTA also contains a less known population: glutamatergic (VGluT2) neurons. Direct activation of VGluT2 soma evokes rewarding behaviors, while stimulation of their axonal projections to the Nucleus Accumbens (NAc) and the Lateral Habenula (LHb) evokes aversive behaviors. Here, a systematic investigation of the VTAV ^GluT2+ population response to aversive or rewarding conditioning facilitated our understanding these conflicting properties. We recorded calcium signals from VTA glutamatergic population neurons using fiber photometry in VGluT2-cre mice to investigate how the VTA glutamatergic neuronal population was recruited by aversive and rewarding stimulation, both during unconditioned and conditioned protocols. Our results revealed that, as a population, VTA ^VGluT2+ neurons responded similarly to unconditioned-aversive and unconditioned-rewarding stimulation. During aversive and rewarding conditioning, the CS-evoked responses gradually increased across trials whilst the US-evoked response remained stable. Retrieval 24 h after conditioning, during which mice received only CS presentation, resulted in VTAV ^GluT2+ neurons strongly responding to CS presentation and to the expected-US but only for aversive conditioning. The inputs and outputs of VTA ^VGluT2+ neurons were then investigated using Cholera Toxin B (CTB) and rabies virus, and we propose based on all results that VTAV ^GluT2+ neurons specialized function may be partially due to their connectivity.