Influence of Brainstem's Area A5 on Sympathetic Outflow and Cardiorespiratory Dynamics.

Area A5 is a noradrenergic cell group in the brain stem characterised by its important role in triggering sympathetic activity, exerting a profound influence on the sympathetic outflow, which is instrumental in the modulation of cardiovascular functions, stress responses and various other physiological processes that are crucial for adaptation and survival mechanisms. Understanding the role of area A5, therefore, not only provides insights into the basic functioning of the sympathetic nervous system but also sheds light on the neuronal basis of a number of autonomic responses. In this review, we look deeper into the specifics of area A5, exploring its anatomical connections, its neurochemical properties and the mechanisms by which it influences sympathetic nervous system activity and cardiorespiratory regulation and, thus, contributes to the overall dynamics of the autonomic function in regulating body homeostasis.

Central Autonomic Mechanisms Involved in the Control of Laryngeal Activity and Vocalization.

In humans, speech is a complex process that requires the coordinated involvement of various components of the phonatory system, which are monitored by the central nervous system. The larynx in particular plays a crucial role, as it enables the vocal folds to meet and converts the exhaled air from our lungs into audible sounds. Voice production requires precise and sustained exhalation, which generates an air pressure/flow that creates the pressure in the glottis required for voice production. Voluntary vocal production begins in the laryngeal motor cortex (LMC), a structure found in all mammals, although the specific location in the cortex varies in humans. The LMC interfaces with various structures of the central autonomic network associated with cardiorespiratory regulation to allow the perfect coordination between breathing and vocalization. The main subcortical structure involved in this relationship is the mesencephalic periaqueductal grey matter (PAG). The PAG is the perfect link to the autonomic pontomedullary structures such as the parabrachial complex (PBc), the Kölliker-Fuse nucleus (KF), the nucleus tractus solitarius (NTS), and the nucleus retroambiguus (nRA), which modulate cardiovascular autonomic function activity in the vasomotor centers and respiratory activity at the level of the generators of the laryngeal-respiratory motor patterns that are essential for vocalization. These cores of autonomic structures are not only involved in the generation and modulation of cardiorespiratory responses to various stressors but also help to shape the cardiorespiratory motor patterns that are important for vocal production. Clinical studies show increased activity in the central circuits responsible for vocalization in certain speech disorders, such as spasmodic dysphonia because of laryngeal dystonia.

CardioRVAR: A New R Package and Shiny Application for the Evaluation of Closed-Loop Cardiovascular Interactions.

CardioRVAR is a new R package designed for the complete evaluation of closed-loop cardiovascular interactions and baroreflex sensitivity estimated from continuous non-invasive heart rate and blood pressure recordings. In this work, we highlight the importance of this software tool in the context of human cardiovascular and autonomic neurophysiology. A summary of the main algorithms that CardioRVAR uses are reviewed, and the workflow of this package is also discussed. We present the results obtained from this tool after its application in three clinical settings. These results support the potential clinical and scientific applications of this tool. The open-source tool can be downloaded from a public GitHub repository, as well as its specific Shiny application, CardioRVARapp. The open-source nature of the tool may benefit the future continuation of this work.

Teaching the physiology of the human body in non-formal spaces: pilot experience of a Service-Learning methodology and the interaction between students of different educational levels.

Research institutes and universities have strengthened the development of biomedicine outreach activities, constituing a non-formal education system of science literacy, although with little commitment from undergraduate students. However, as a Service-Learning methodology, these outreach activities could work as a tool for the acquisition of skills by students of Health Science Degrees. Described here is the development of the workshop entitled "Exploring the human body" at the Biodonostia Health Research Institute and the pilot experience of its implementation as a Service-Learning activity at the University of Málaga. Firstly, 359 secondary education students were mentored by Ph.D. students through a 5-station workshop with experiments and activities related to the physiology of the human body. Then, 301 undergraduate students of Medicine and Nursing Degrees advised 965 secondary education students. Both groups of students assessed the workshop via questionnaires and a debriefing. The data showed an overall score of 4.6 out of 5 for the workshop. Undergraduate students reported a positive impact on their academic background (4.8 out of 5), mainly due to the improvement of oral communication skills (34%). Therefore, this methodology could be a valid and applicable tool to develop the cross-disciplinary competences of undergraduate students.

Impact of music performance anxiety on cardiovascular blood pressure responses, autonomic tone and baroreceptor sensitivity to a western classical music piano-concert.

Introduction: Music Performance Anxiety (MPA) is a prevalent condition among musicians that can manifest both psychologically and physiologically, leading to impaired musical performance. Physiologically, MPA is characterized by excessive muscular and/or autonomic tone. This study focuses on the cardiovascular blood pressure responses, autonomic tone and baroreceptor sensitivity changes that occur during musical performance due to MPA. Methods: Six professional pianists perform a piece for piano written only for the left hand by Alexander Scriabin. The following parameters have been studied during the performance: ECG, non-invasive beat to beat continuous arterial blood pressure and skin conductance. Sympathetic and parasympathetic autonomic flow was studied with Wigner-Ville analysis (W-V) from R-R ECG variability, and baroreceptor sensitivity with the Continuous Wavelet Transform (CWT). Results: During the concert a significant increase of heart rate, systolic, mean and diastolic arterial pressure were observed. No significant differences were found in skin conductance. The W-V analysis, which studies frequency changes in the time domain, shows a significant increase of sympathetic flow and a decrease of parasympathetic flow during the concert which is associated with a significant decrease in sympathetic and vagal baroreceptor sensitivity. Discussion: The study of cardiac variability using the Wigner-Ville analysis may be a suitable method to assess the autonomic response in the context of MPA, and could be used as biofeedback in personalized multimodal treatments.

Insulin-like Growth Factor II Prevents MPP+ and Glucocorticoid Mitochondrial-Oxidative and Neuronal Damage in Dopaminergic Neurons.

Stress seems to contribute to Parkinson's disease (PD) neuropathology, probably by dysregulation of the hypothalamic-pituitary-adrenal axis. Key factors in this pathophysiology are oxidative stress and mitochondrial dysfunction and neuronal glucocorticoid-induced toxicity. The insulin-like growth factor II (IGF-II), a pleiotropic hormone, has shown antioxidant and neuroprotective effects in some neurodegenerative disorders. Our aim was to examine the protective effect of IGF-II on a dopaminergic cellular combined model of PD and mild to moderate stress measuring oxidative stress parameters, mitochondrial and neuronal markers, and signalling pathways. IGF-II counteracts the mitochondrial-oxidative damage produced by the toxic synergistic effect of corticosterone and 1-methyl-4-phenylpyridinium, protecting dopaminergic neurons from death and neurodegeneration. IGF-II promotes PKC activation and nuclear factor (erythroid-derived 2)-like 2 antioxidant response in a glucocorticoid receptor-dependent pathway, preventing oxidative cell damage and maintaining mitochondrial function. Thus, IGF-II is a potential therapeutic tool for treatment and prevention of disease progression in PD patients suffering mild to moderate emotional stress.

Pontine A5 region modulation of the cardiorespiratory response evoked from the midbrain dorsolateral periaqueductal grey.

Connections between the midbrain dorsolateral periaqueductal grey (dlPAG) and the pontine A5 region have been shown. The stimulation of both regions evokes similar cardiovascular responses: tachycardia and hypertension. Accordingly, we have studied the interactions between dlPAG and A5 region in spontaneously breathing anesthetized rats. dlPAG was electrically stimulated (20-30 µA 1-ms pulses were given for 5 s at 100 Hz). Changes in the evoked cardiorespiratoy response were analysed before and after ipsilateral microinjections of muscimol (GABAergic agonist, 50 nl, 0.25 nmol, 5 s) within the A5 region. Electrical stimulation of the dlPAG produces, in the rat, a response characterized by tachypnoea (p < 0.001), hypertension (p < 0.001) and tachycardia (p < 0.001). The increase in respiratory rate was due to a decrease in expiratory time (p < 0.01). Pharmacological inhibition of the A5 region with muscimol produced a marked reduction of the tachycardia (p < 0.001) and the tachypnoea (p < 0.01) evoked from the dlPAG. Finally, to assess functional interactions between A5 and dlPAG, extracellular activity of putative A5 neurones were recorded during dlPAG electrical stimulation. Forty A5 cells were recorded, 16 of which were affected by dlPAG stimulation (40%). 4 cells showed activation, 5 cells excitation and 7 cells decreased spontaneous activity to dlPAG stimulation (p < 0.001). These results confirm a link between the A5 region and dlPAG. The potential role of these connections in the modulation of dlPAG evoked cardiorespiratory responses and their possible clinical implications are discussed.

Role of the parabrachial complex in the cardiorespiratory response evoked from hypothalamic defense area stimulation in the anesthetized rat.

To analyze the role of parabrachial complex (PBc) in the modulation of cardiorespiratory response evoked from the hypothalamic defense area (HDA), cardiorespiratory changes were analyzed in spontaneously breathing anesthetised rats in response to electrical stimulation of the HDA (1 ms pulses, 30-50 microA, 100 Hz for 5 s) before and after the microinjection of muscimol (50 nl, 0.25 nmol, 5 s) within the PBc. HDA stimulation evoked an inspiratory facilitatory response, consisting of an increase in respiratory rate (p<0.001) due to a decrease in expiratory time (p<0.01). The respiratory response was accompanied by a pressor (p<0.001) and a tachycardic (p<0.001) response. Muscimol microinjection within the lateral parabrachial region (lPB) abolished the respiratory response to HDA stimulation (p<0.01) and decreased the pressor response (p<0.05). Muscimol within the medial parabrachial region and Kölliker-Fuse (mPB-KF) decreased the magnitude of the pressor (p<0.01) and tachycardic (p<0.05) responses to HDA stimulation. The respiratory response persisted unchanged. Finally, extracellular recording of putative neurons from these regions were obtained during HDA stimulation to confirm functional interaction between HDA and parabrachial regions. 105 pontine cells were recorded during HDA stimulation, 57 from the lPB and 48 from the mPB-KF. In mPB-KF 34/48 (71%) and in lPB 38/57 (67%) cells were influenced from HDA. The results indicate that neurons from different regions of the PBc have an important function in mediating the cardiorespiratory response evoked from the HDA. The possible mechanisms involved in these interactions are discussed.