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The pre-Bötzinger complex (preBötC), a key primary generator of the inspiratory breathing rhythm, contains neurons that project directly to facial nucleus (7n) motoneurons to coordinate orofacial and nasofacial activity. To further understand the identity of 7n-projecting preBötC neurons, we used a combination of optogenetic viral transgenic approaches to demonstrate that selective photoinhibition of these neurons affects mystacial pad activity, with minimal effects on breathing. These effects are altered by the type of anesthetic employed and also between anesthetized and conscious states. The population of 7n-projecting preBötC neurons we transduced consisted of both excitatory and inhibitory neurons that also send collaterals to multiple brainstem nuclei involved with the regulation of autonomic activity. We show that modulation of subgroups of preBötC neurons, based on their axonal projections, is a useful strategy to improve our understanding of the mechanisms that coordinate and integrate breathing with different motor and physiological behaviors. This is of fundamental importance, given that abnormal respiratory modulation of autonomic activity and orofacial behaviors have been associated with the development and progression of diseases., Competing Interests: MM, AW, AC, JB, SC, SM, CM, RB, AA No competing interests declared, (© 2023, Melo et al.)

Spinal cord injury (SCI) leads not only to major impairments in sensorimotor control but also to dramatic dysregulation of autonomic functions including major cardiovascular disturbances. Consequently, individuals with SCI endure daily episodic hypo/hypertension and are at increased risk for cardiovascular disease. Several studies have suggested that an intrinsic spinal coupling mechanism between motor and sympathetic neuronal networks exist and that propriospinal cholinergic neurons may be responsible for a synchronized activation of both somatic and sympathetic outputs. We therefore investigated in the present study, the effect of cholinergic muscarinic agonists on cardiovascular parameters in freely moving adult rats after SCI. Female Sprague-Dawley rats were implanted with radiotelemetry sensors for long-term in vivo monitoring of blood pressure (BP). From BP signal, we calculated heart rate (HR) and respiratory frequency. We first characterized the physiological changes occurring after a SCI performed at the T3-T4 level in our experimental model system. We then investigated the effects on BP, HR and respiration, of the muscarinic agonist oxotremorine using one variant that crossed the blood brain barrier (Oxo-S) and one that does not (Oxo-M) in both Pre- and Post-SCI animals. After SCI, both HR and respiratory frequency increased. BP values exhibited an immediate profound drop before progressively increasing over the three-week post-lesion period but remained below control values. A spectral analysis of BP signal revealed the disappearance of the low frequency component of BP (0.3-0.6 Hz) referred to as Mayer waves after SCI. In Post-SCI animals, central effects mediated by Oxo-S led to an increase in HR and MAP, a slowdown in respiratory frequency and to an increased power in the 0.3-0.6 Hz frequency band. This study unravels some of the mechanisms by which muscarinic activation of spinal neurons could contribute to partial restoration of BP after SCI., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Rett syndrome (RTT) is a severe neurodevelopmental disorder that arise from de novo mutations in the X-linked gene MECP2 (methyl-CpG-binding protein 2). Circulating levels of the adipocyte hormone leptin are elevated in RTT patients and rodent models of the disease. Leptin targets a large number of brain structures and regulates a wide range of developmental and physiological functions which are altered in RTT. We hypothesized that elevated leptin levels might contribute to RTT pathogenesis. Accordingly, we show that pharmacological antagonism of leptin or genetic reduction of leptin production prevents the degradation of health status, weight loss and the progression of breathing and locomotor deficits. At the neuronal level, the anti-leptin strategies rescue the hippocampal excitatory/inhibitory imbalance and synaptic plasticity impairment. Targeting leptin might therefore represent a new approach for RTT treatment.

Twenty-five years ago, a new physiological preparation called the working heart-brainstem preparation (WHBP) was introduced with the claim it would provide a new platform allowing studies not possible before in cardiovascular, neuroendocrine, autonomic and respiratory research. Herein, we review some of the progress made with the WHBP, some advantages and disadvantages along with potential future applications, and provide photographs and technical drawings of all the customised equipment used for the preparation. Using mice or rats, the WHBP is an in situ experimental model that is perfused via an extracorporeal circuit benefitting from unprecedented surgical access, mechanical stability of the brain for whole cell recording and an uncompromised use of pharmacological agents akin to in vitro approaches. The preparation has revealed novel mechanistic insights into, for example, the generation of distinct respiratory rhythms, the neurogenesis of sympathetic activity, coupling between respiration and the heart and circulation, hypothalamic and spinal control mechanisms, and peripheral and central chemoreceptor mechanisms. Insights have been gleaned into diseases such as hypertension, heart failure and sleep apnoea. Findings from the in situ preparation have been ratified in conscious in vivo animals and when tested have translated to humans. We conclude by discussing potential future applications of the WHBP including two-photon imaging of peripheral and central nervous systems and adoption of pharmacogenetic tools that will improve our understanding of physiological mechanisms and reveal novel mechanisms that may guide new treatment strategies for cardiorespiratory diseases., (© 2022 The Authors. The Journal of Physiology published by John Wiley & Sons Ltd on behalf of The Physiological Society.)

Behavioral phenotyping devices have been successfully used to build ethograms, but many aspects of behavior remain out of reach of available phenotyping systems. We now report on a novel device, which consists in an open-field platform resting on highly sensitive piezoelectric (electromechanical) pressure-sensors, with which we could detect the slightest movements (up to individual heart beats during rest) from freely moving rats and mice. The combination with video recordings and signal analysis based on time-frequency decomposition, clustering, and machine learning algorithms provided non-invasive access to previously overlooked behavioral components. The detection of shaking/shivering provided an original readout of fear, distinct from but complementary to behavioral freezing. Analyzing the dynamics of momentum in locomotion and grooming allowed to identify the signature of gait and neurodevelopmental pathological phenotypes. We believe that this device represents a significant progress and offers new opportunities for the awaited advance of behavioral phenotyping., (© 2021. The Author(s), under exclusive licence to American College of Neuropsychopharmacology.)