Electrodermal and central measures of the tonic orienting reflex (OR).

Sokolov described both phasic and tonic aspects of the Orienting Reflex (OR), but subsequent research and theory development has focussed primarily on the phasic OR at the expense of the tonic OR. The present study used prestimulus skin conductance level (SCL) during a dishabituation paradigm to model the tonic OR, examining its amplitude patterning over repeated standard stimulus presentations and a change stimulus. We expected sensitisation (increased amplitude) following the initial and change trials, and habituation (decrement) over the intervening trials. Prestimulus EEG alpha level was explored as a potential central measure of the tonic OR (as an inverse correlate), examining its pattern over stimulus repetition and change in relation to the SCL model. We presented a habituation series of innocuous auditory stimuli to two groups (each N = 20) at different ISIs (Long 13-15 s and Short 5-7 s) and recorded electrodermal and EEG data during two counterbalanced conditions; Indifferent: no task requirements; Significant: silent counting. Across groups and conditions, prestimulus SCLs and alpha amplitudes generally showed the expected trials patterns, confirming our main hypotheses. Findings have important implications for including the assessment of Sokolov's tonic OR in modelling central and autonomic nervous system interactions of fundamental attention and learning processes.

Optogenetic stimulation of neurons in the anterior cingulate cortex induces changes in intravesical bladder pressure and the micturition reflex.

Lower urinary tract (LUT) function is controlled by the central nervous system, including higher-order cognitive brain regions. The anterior cingulate cortex (ACC) is one of these regions, but the role of its activity in LUT function remains poorly understood. In the present study, we conducted optogenetic experiments to manipulate neural activity in mouse ACC while monitoring bladder pressure to elucidate how the activity of ACC regulates LUT function. Selective optogenetic stimulation of excitatory neurons in ACC induced a sharp increase in bladder pressure, whereas activation of inhibitory neurons in ACC prolonged the interval between bladder contractions. Pharmacological manipulation of ACC also altered bladder contractions, consistent with those observed in optogenetic experiments. Optogenetic mapping of the cortical area responsible for eliciting the increase in bladder pressure revealed that stimulation to ACC showed more potent effects than the neighboring motor cortical areas. These results suggest that ACC plays a crucial role in initiating the bladder pressure change and the micturition reflex. Thus, the balance between excitation and inhibition in ACC may regulate the reflex bidirectionally.

A vagal reflex evoked by airway closure.

Airway integrity must be continuously maintained throughout life. Sensory neurons guard against airway obstruction and, on a moment-by-moment basis, enact vital reflexes to maintain respiratory function1,2. Decreased lung capacity is common and life-threatening across many respiratory diseases, and lung collapse can be acutely evoked by chest wall trauma, pneumothorax or airway compression. Here we characterize a neuronal reflex of the vagus nerve evoked by airway closure that leads to gasping. In vivo vagal ganglion imaging revealed dedicated sensory neurons that detect airway compression but not airway stretch. Vagal neurons expressing PVALB mediate airway closure responses and innervate clusters of lung epithelial cells called neuroepithelial bodies (NEBs). Stimulating NEBs or vagal PVALB neurons evoked gasping in the absence of airway threats, whereas ablating NEBs or vagal PVALB neurons eliminated gasping in response to airway closure. Single-cell RNA sequencing revealed that NEBs uniformly express the mechanoreceptor PIEZO2, and targeted knockout of Piezo2 in NEBs eliminated responses to airway closure. NEBs were dispensable for the Hering-Breuer inspiratory reflex, which indicated that discrete terminal structures detect airway closure and inflation. Similar to the involvement of Merkel cells in touch sensation3,4, NEBs are PIEZO2-expressing epithelial cells and, moreover, are crucial for an aspect of lung mechanosensation. These findings expand our understanding of neuronal diversity in the airways and reveal a dedicated vagal pathway that detects airway closure to help preserve respiratory function.

Dysphoric milk ejection reflex among Japanese mothers: a self-administered survey.

BACKGROUND: The dysphoric milk ejection reflex (D-MER) is a reflex that causes temporary discomfort during milk ejection. D-MER develops due to the effects of hormones involved in lactation, and it has been reported that it is a physiological symptom different from postpartum depression, but the actual situation is unknown in Japan. METHODS: This study was conducted using a self-administered, anonymous survey of mothers of children who had undergone health checkups at three years of age at five health centers in Kagoshima city and aimed to clarify the reality and perceptions of mothers regarding D-MER. The survey period was from May to September, 2022. The questionnaires were distributed to 389 mothers, and 216 (55.5% recovery rate) responses were received, of which 202 (valid response rate 93.5%) were included in the analysis. RESULTS: Regarding the experience of D-MER, 202 mothers in the study population had given birth to a total of 403 children and experienced D-MER when breastfeeding 62 children (15.4%). Of the 202 mothers included in the analysis, 47 (23.3%) answered that they had experienced D-MER with at least one child while breastfeeding. Sixty-six mothers (32.7%) knew about D-MER. Compared to those who had not experienced D-MER, those who had experienced D-MER had significantly higher scores on the items related to having had trouble breastfeeding (odds ratio (OR]: 3.78; 95% confidence interval (CI]: 1.57, 9.09) and knowing about D-MER (OR 2.41; 95% CI 1.20, 4.84). Regarding symptoms, irritability (n = 24, 51.1%), anxiety (n = 22, 46.8%), and sadness (n = 18, 38.3%) ranked high. Coping strategies included distraction, focusing on the child, and, in some cases, cessation of breastfeeding. Thirty mothers (63.8%) answered that they did not consult anyone, citing reasons such as a belief that no one would be likely to understand their symptoms, and that they could not sufficiently explain their symptoms. CONCLUSION: The low level of awareness of D-MER suggests that it is necessary to inform and educate mothers and the public about the physiological symptoms of D-MER. Moreover, it is necessary to listen to the feelings of mothers with D-MER and support them in coping with their symptoms.

Distinguishing reflex from non-reflex responses elicited by transcutaneous spinal stimulation targeting the lumbosacral cord in healthy individuals.

Transcutaneous spinal stimulation (TSS) studies rely on the depolarization of afferent fibers to provide input to the spinal cord; however, this has not been routinely ascertained. Thus, we aimed to characterize the types of responses evoked by TSS and establish paired-pulse ratio cutoffs that distinguish posterior root reflexes, evoked by stimulation of afferent nerve fibers, from motor responses, evoked by stimulation of efferent nerve fibers. Twelve neurologically intact participants (six women) underwent unipolar TSS (cathode over T11-12 spinal processes, anode paraumbilically) while resting supine. In six participants, unipolar TSS was repeated 2-3 months later and also compared to a bipolar TSS configuration (cathode 2.5 cm below T11-12, anode 5 cm above cathode). EMG signals were recorded from 16 leg muscles. A paired-pulse paradigm was applied at interstimulus intervals (ISIs) of 25, 50, 100, 200, and 400 ms. Responses were categorized by three assessors into reflexes, motor responses, or their combination (mixed responses) based on the visual presence/absence of paired-pulse suppression across ISIs. The paired-pulse ratio that best discriminated between response types was derived for each ISI. These cutoffs were validated by repeating unipolar TSS 2-3 months later and with bipolar TSS. Unipolar TSS evoked only reflexes (90%) and mixed responses (10%), which were mainly recorded in the quadriceps muscles (25-42%). Paired-pulse ratios of 0.51 (25-ms ISI) and 0.47 (50-ms ISI) best distinguished reflexes from mixed responses (100% sensitivity, > 99.2% specificity). These cutoffs performed well in the repeated unipolar TSS session (100% sensitivity, > 89% specificity). Bipolar TSS exclusively elicited reflexes which were all correctly classified. These results can be utilized in future studies to ensure that the input to the spinal cord originates from the depolarization of large afferents. This knowledge can be applied to improve the design of future neurophysiological studies and increase the fidelity of neuromodulation interventions.

Dysphoric Milk Ejection Reflex in Human Lactation: An Integrative Literature Review.

BACKGROUND: Dysphoric Milk Ejection Reflex is an understudied condition of lactation involving emotional dysregulation during letdown or milk ejection. Affected individuals may experience transient feelings of helplessness, melancholy, and general unhappiness. RESEARCH AIM: To evaluate the scope of published literature on Dysphoric Milk Ejection Reflex. METHOD: Whittemore and Knafl's methodology guided this integrative review. Five databases were searched for primary research, summaries, and editorials on Dysphoric Milk Ejection Reflex in lactating individuals. Literature searched also included websites, pamphlets, and conference proceedings via Google and Google Scholar. A total of 11 articles, from five different countries, met inclusion criteria for review. RESULTS: Studies on Dysphoric Milk Ejection Reflex and negative emotional sensations during lactation were synthesized under five conceptual umbrellas: (1) Experiences, Sensations, and Symptom Management; (2) Biological Underpinnings; (3) Influence on Maternal Role and Breastfeeding Self-Efficacy; (4) Support, Understanding, and Awareness; and (5) Reduction and Cessation of Breastfeeding. CONCLUSION: Dysphoric Milk Ejection Reflex is a neurobiological condition characterized by low mood and negative feelings during milk ejection throughout lactation. Dysphoric Milk Ejection Reflex is linked to maternal psychological distress and breastfeeding discontinuation. Priority areas for future research include biological origins and interventions aimed at prevention, symptom control, and greater awareness of the condition on a more international scope.

The blink reflex and its modulation - Part 2: Pathophysiology and clinical utility.

The blink reflex (BR) is integrated at the brainstem; however, it is modulated by inputs from various structures such as the striatum, globus pallidus, substantia nigra, and nucleus raphe magnus but also from afferent input from the peripheral nervous system. Therefore, it provides information about the pathophysiology of numerous peripheral and central nervous system disorders. The BR is a valuable tool for studying the integrity of the trigemino-facial system, the relevant brainstem nuclei, and circuits. At the same time, some neurophysiological techniques applying the BR may indicate abnormalities involving structures rostral to the brainstem that modulate or control the BR circuits. This is a state-of-the-art review of the clinical application of BR modulation; physiology is reviewed in part 1. In this review, we aim to present the role of the BR and techniques related to its modulation in understanding pathophysiological mechanisms of motor control and pain disorders, in which these techniques are diagnostically helpful. Furthermore, some BR techniques may have a predictive value or serve as a basis for follow-up evaluation. BR testing may benefit in the diagnosis of hemifacial spasm, dystonia, functional movement disorders, migraine, orofacial pain, and psychiatric disorders. Although the abnormalities in the integrity of the BR pathway itself may provide information about trigeminal or facial nerve disorders, alterations in BR excitability are found in several disease conditions. BR excitability studies are suitable for understanding the common pathophysiological mechanisms behind various clinical entities, elucidating alterations in top-down inhibitory systems, and allowing for follow-up and quantitation of many neurological syndromes.

Short-term and long-term effects of unilateral external carotid artery ligation on orofacial functions in rats.

The external carotid artery (ECA) plays a major role in supplying blood to the head and neck. Although impeded blood flow in the ECA is expected to affect orofacial functions, few studies have shown how blood flow obstruction in the ECA contributes to impairment of these functions, including chewing and swallowing. This study was performed to investigate the effects of ECA ligation (ECAL) on immediate and long-term changes in masticatory and swallowing functions as well as the jaw-opening reflex evoked in the digastric muscle. The experiments were carried out using male Sprague-Dawley rats. In the acute experiment, the digastric reflex evoked by low-threshold electrical stimulation of the inferior alveolar nerve and the swallow reflex, identified by digastric and thyrohyoid electromyographic (EMG) bursts, were compared between before and 1 h after ECAL. The chronic experiment was conducted on freely moving rats. EMGs of the masseter, digastric, and thyrohyoid muscles were chronically recorded. The long-term effects of ECAL on behavior and muscle histology were compared between rats with an intact ECA and rats with ECAL. In the acute experiment, the peak amplitude of the digastric reflex on the ECAL side was significantly decreased 1 h after ECAL. In the chronic experiment, although most parameters of the masticatory and swallowing EMGs were not significantly different between the groups, the results suggest wide variation of the effect of ECAL on the muscles. Blood supply compensation from collaterals of the internal carotid artery may be permanent in some animals.NEW & NOTEWORTHY The inhibitory effect of unilateral external carotid artery ligation (ECAL) on the ipsilateral digastric reflex was small but evident. Most parameters of masticatory and swallowing muscle activity were not significantly different after ECAL. Wide variation was noted in the effect of ECAL on the ipsilateral muscle activity. Blood supply compensation from collaterals of the internal carotid artery may occur in response to the impaired blood flow.

A ganglionic intestinointestinal reflex activated by acute noxious challenge.

To investigate noxious stimulation-responsive neural circuits that could influence the gut, we recorded from intestinally directed (efferent) nerve filaments dissected from mesenteric nerves close to the small intestine in anesthetized rats. These exhibited baseline multiunit activity that was almost unaffected by vagotomy (VagX) and reduced only slightly by cutting the splanchnic nerves. The activity was halved by hexamethonium (Hex) treatment. When an adjacent gut segment received an intraluminal stimulus 2,4,6-trinitrobenzenesulfonate (TNBS) in 30% ethanol, mesenteric efferent nerve activity increased for more than 1 h. The increased activity was almost unaffected by bilateral vagotomy or splanchnic nerve section, indicating a lack of central nervous involvement, but it was 60% reduced by hexamethonium. Spike sorting discriminated efferent single and predominantly single-unit spike trains that responded to TNBS, were unaffected by splachnectomy but were silenced by hexamethonium. After noxious stimulation of one segment, the adjacent segment showed no evidence of suppression of gut motility or vasoconstriction. We conclude that luminal application of a noxious stimulus to the small intestine activates an entirely peripheral, intestinointestinal reflex pathway. This pathway involves enteric intestinofugal neurons that excite postganglionic sympathetic neurons via a nicotinic synapse. We suggest that the final sympathetic efferent neurons that respond to a tissue damaging stimulus are distinct from vasoconstrictor, secretomotor, and motility inhibiting neurons.NEW & NOTEWORTHY An intraluminal noxious chemical stimulus applied to one segment of small intestine increased mesenteric efferent nerve activity to an adjacent segment. This was identified as a peripheral ganglionic reflex that did not require vagal or spinal connections. Hexamethonium blocked most, but not all, ongoing and reflex mesenteric efferent activity. The prevertebral sympathetic efferent neurons that are activated likely affect inflammatory and immune functions of other gut segments.

Altered locomotor muscle metaboreflex control of ventilation in patients with COPD.

We investigated the locomotor muscle metaboreflex control of ventilation, circulation, and dyspnea in patients with chronic obstructive pulmonary disease (COPD). Ten patients [forced expiratory volume in 1 second (FEV1; means ± SD) = 43 ± 17% predicted] and nine age- and sex-matched controls underwent 1) cycling exercise followed by postexercise circulatory occlusion (PECO) to activate the metaboreflex or free circulatory flow to inactivate it, 2) cold pressor test to interpret whether any altered reflex response was specific to the metaboreflex arc, and 3) muscle biopsy to explore the metaboreflex arc afferent side. We measured airflow, dyspnea, heart rate, arterial pressure, muscle blood flow, and vascular conductance during reflexes activation. In addition, we measured fiber types, glutathione redox balance, and metaboreceptor-related mRNAs in the vastus lateralis. Metaboreflex activation increased ventilation versus free flow in patients (∼15%, P < 0.020) but not in controls (P > 0.450). In contrast, metaboreflex activation did not change dyspnea in patients (P = 1.000) but increased it in controls (∼100%, P < 0.001). Other metaboreflex-induced responses were similar between groups. Cold receptor activation increased ventilation similarly in both groups (P = 0.46). Patients had greater type II skeletal myocyte percentage (14%, P = 0.010), lower glutathione ratio (-34%, P = 0.015), and lower nerve growth factor (NGF) mRNA expression (-60%, P = 0.031) than controls. Therefore, COPD altered the locomotor muscle metaboreflex control of ventilation. It increased type II myocyte percentage and elicited redox imbalance, potentially producing more muscle metaboreceptor stimuli. Moreover, it decreased NGF expression, suggesting a downregulation of metabolically sensitive muscle afferents.NEW & NOTEWORTHY This study's integrative physiology approach provides evidence for a specific alteration in locomotor muscle metaboreflex control of ventilation in patients with COPD. Furthermore, molecular analyses of a skeletal muscle biopsy suggest that the amount of muscle metaboreceptor stimuli derived from type II skeletal myocytes and redox imbalance overcame a downregulation of metabolically sensitive muscle afferents.

Identifying essential factors for energy-efficient walking control across a wide range of velocities in reflex-based musculoskeletal systems.

Humans can generate and sustain a wide range of walking velocities while optimizing their energy efficiency. Understanding the intricate mechanisms governing human walking will contribute to the engineering applications such as energy-efficient biped robots and walking assistive devices. Reflex-based control mechanisms, which generate motor patterns in response to sensory feedback, have shown promise in generating human-like walking in musculoskeletal models. However, the precise regulation of velocity remains a major challenge. This limitation makes it difficult to identify the essential reflex circuits for energy-efficient walking. To explore the reflex control mechanism and gain a better understanding of its energy-efficient maintenance mechanism, we extend the reflex-based control system to enable controlled walking velocities based on target speeds. We developed a novel performance-weighted least squares (PWLS) method to design a parameter modulator that optimizes walking efficiency while maintaining target velocity for the reflex-based bipedal system. We have successfully generated walking gaits from 0.7 to 1.6 m/s in a two-dimensional musculoskeletal model based on an input target velocity in the simulation environment. Our detailed analysis of the parameter modulator in a reflex-based system revealed two key reflex circuits that have a significant impact on energy efficiency. Furthermore, this finding was confirmed to be not influenced by setting parameters, i.e., leg length, sensory time delay, and weight coefficients in the objective cost function. These findings provide a powerful tool for exploring the neural bases of locomotion control while shedding light on the intricate mechanisms underlying human walking and hold significant potential for practical engineering applications.

Identifying vagal sensory neurons driving the Bezold-Jarisch reflex.

Homeostatic reflexes are crucial for life, but the subpopulations of sensory neurons that stimulate these reflexes are largely unknown. A recent paper from Lovelace, Ma, and colleagues identified a population of sensory neurons in the cardiac ventricle that underlies the Bezold-Jarisch reflex and triggers syncope (fainting).

Muscle metaboreflex stimulates the cardiac sympathetic afferent reflex causing positive feedback amplification of sympathetic activity: effect of heart failure.

Exercise intolerance is a hallmark symptom of heart failure and to a large extent stems from reductions in cardiac output that occur due to the inherent ventricular dysfunction coupled with enhanced muscle metaboreflex-induced functional coronary vasoconstriction, which limits increases in coronary blood flow. This creates a further mismatch between O2 delivery and O2 demand, which may activate the cardiac sympathetic afferent reflex (CSAR), causing amplification of the already increased sympathetic activity in a positive-feedback fashion. We used our chronically instrumented conscious canine model to evaluate if chronic ablation of afferents responsible for the CSAR would attenuate the gain of muscle metaboreflex before and after induction of heart failure. After afferent ablation, the gain of the muscle metaboreflex control of mean arterial pressure was significantly reduced before (-239.5 ± 16 to -95.2 ± 8 mmHg/L/min) and after the induction of heart failure (-185.6 ± 14 to -95.7 ± 12 mmHg/L/min). Similar results were observed for the strength (gain) of muscle metaboreflex control of heart rate, cardiac output, and ventricular contractility. Thus, we conclude that the CSAR contributes significantly to the strength of the muscle metaboreflex in normal animals with heart failure serving as an effective positive-feedback amplifier thereby further increasing sympathetic activity.NEW & NOTEWORTHY The powerful pressor responses from the CSAR arise via O2 delivery versus O2 demand imbalance. Muscle metaboreflex activation (MMA) simultaneously elicits coronary vasoconstriction (which is augmented in heart failure) and profound increases in cardiac work thereby upsetting oxygen balance. Whether MMA activates the CSAR thereby amplifying MMA responses is unknown. We observed that removal of the CSAR afferents attenuated the strength of the muscle metaboreflex in normal and subjects with heart failure.

Vagus nerve SARS-CoV-2 infection and inflammatory reflex dysfunction: Is there a causal relationship?

Autonomic dysfunction is a clinical hallmark of infection caused by SARS-CoV-2, but the underlying mechanisms are unknown. The vagus nerve inflammatory reflex is an important, well-characterized mechanism for the reflexive suppression of cytokine storm, and its experimental or clinical impairment facilitates the onset and progression of hyperinflammation. Recent pathological evidence from COVID-19 victims reveals viral infection and inflammation in the vagus nerve and associated nuclei in the medulla oblongata. Although it has been suggested that vagus nerve inflammation in these patients mediates dysregulated respiration, whether it also contributes to dysfunction of the vagus nerve inflammatory reflex has not been addressed. Because lethality and tissue injury in acute COVID-19 are characterized by cytokine storm, it is plausible to consider evidence that impairment of the inflammatory reflex may contribute to overproduction of cytokines and resultant hyperinflammatory pathogenesis. Accordingly, here the authors discuss the inflammatory reflex, the consequences of its dysfunction in COVID-19, and whether there are opportunities for therapeutic intervention.

Comparison of acute responses in spinal excitability between older and young people after neuromuscular electrical stimulation.

PURPOSE: This study aims at comparing acute responses in spinal excitability, as measured by H-reflex, between older and young individuals, following a single session of NMES superimposed onto voluntary isometric contractions of the ankle plantar-flexor muscles (NMES+), with respect to passive NMES (pNMES) and voluntary isometric contractions only (ISO). METHODS: Thirty-two volunteers, 16 older (OLDER) and 16 young (YOUNG), were asked to sustain a constant force at 20% of maximal voluntary isometric contraction (MVIC) of the ankle plantar-flexor muscles in the dominant limb during each of the 3 conditions (NMES+ , pNMES and ISO). Fifteen repetitions of 6 s were performed, with a resting interval of 6 s between repetitions. Before and after each condition, soleus H-reflexes were elicited by percutaneous electrical stimulation of the posterior tibial nerve and H-reflex amplitudes recorded by surface EMG. RESULTS: In OLDER, H-reflex amplitude did not change following any experimental condition (ISO: p = 0.203; pNMES: p = 0.542; NMES+: p = 0.431) compared to baseline. On the contrary, in YOUNG, H-reflex amplitudes significantly increased (p < 0.000) and decreased (p = 0.001) following NMES+ and pNMES, respectively, while there was no significant change in reflex responses following ISO (p = 0.772). CONCLUSION: The lack of change in H-reflex responses following either NMES+ or pNMES might reflect a reduced ability of older people in modulating spinal excitability after the conditions. Specifically, an age-related alteration in controlling mechanisms at presynaptic level was suggested.

The blink reflex and its modulation - Part 1: Physiological mechanisms.

The blink reflex (BR) is a protective eye-closure reflex mediated by brainstem circuits. The BR is usually evoked by electrical supraorbital nerve stimulation but can be elicited by a variety of sensory modalities. It has a long history in clinical neurophysiology practice. Less is known, however, about the many ways to modulate the BR. Various neurophysiological techniques can be applied to examine different aspects of afferent and efferent BR modulation. In this line, classical conditioning, prepulse and paired-pulse stimulation, and BR elicitation by self-stimulation may serve to investigate various aspects of brainstem connectivity. The BR may be used as a tool to quantify top-down modulation based on implicit assessment of the value of blinking in a given situation, e.g., depending on changes in stimulus location and probability of occurrence. Understanding the role of non-nociceptive and nociceptive fibers in eliciting a BR is important to get insight into the underlying neural circuitry. Finally, the use of BRs and other brainstem reflexes under general anesthesia may help to advance our knowledge of the brainstem in areas not amenable in awake intact humans. This review summarizes talks held by the Brainstem Special Interest Group of the International Federation of Clinical Neurophysiology at the International Congress of Clinical Neurophysiology 2022 in Geneva, Switzerland, and provides a state-of-the-art overview of the physiology of BR modulation. Understanding the principles of BR modulation is fundamental for a valid and thoughtful clinical application (reviewed in part 2) (Gunduz et al., submitted).

Inactivation of the paraventricular nucleus attenuates the cardiogenic sympathetic afferent reflex in the spontaneously hypertensive rat.

BACKGROUND: Myocardial ischemia causes the release of bradykinin, which stimulates cardiac afferents, causing sympathetic excitation and chest pain. Glutamatergic activation of the paraventricular hypothalamic nucleus (PVN) in the spontaneously hypertensive rat (SHR) drives elevated basal sympathetic activity. Thus, we tested the hypothesis that inactivation of the PVN attenuates the elevated reflex response to epicardial bradykinin in the SHR and that ionotropic PVN glutamate receptors mediate the elevated reflex. METHODS: We recorded the arterial pressure and renal sympathetic nerve activity (RSNA) response to epicardial bradykinin application in anesthetized SHR and Wistar Kyoto (WKY) rats before and after PVN microinjection of GABA A agonist muscimol or ionotropic glutamate receptor antagonist kynurenic acid. RESULTS: Muscimol significantly decreased the arterial pressure response to bradykinin from 180.4 ±â€Š5.8 to 119.5 ±â€Š6.9 mmHg in the SHR and from 111.8 ±â€Š7.0 to 84.2 ±â€Š8.3 mmHg in the WKY and the RSNA response from 186.2 ±â€Š7.1 to 142.7 ±â€Š7.3% of baseline in the SHR and from 201.0 ±â€Š11.5 to 160.2 ±â€Š9.3% of baseline in the WKY. Kynurenic acid significantly decreased the arterial pressure response in the SHR from 164.5 ±â€Š5.0 to 126.2 ±â€Š7.7 mmHg and the RSNA response from 189.9 ±â€Š13.7to 168.5 ±â€Š12.7% of baseline but had no effect in the WKY. CONCLUSION: These results suggest that tonic PVN activity is critical for the full manifestation of the CSAR in both the WKY and SHR. Glutamatergic PVN activity contributes to the augmented CSAR observed in the SHR.

A direction-selective cortico-brainstem pathway adaptively modulates innate behaviors.

Sensory cortices modulate innate behaviors through corticofugal projections targeting phylogenetically-old brainstem nuclei. However, the principles behind the functional connectivity of these projections remain poorly understood. Here, we show that in mice visual cortical neurons projecting to the optic-tract and dorsal-terminal nuclei (NOT-DTN) possess distinct response properties and anatomical connectivity, supporting the adaption of an essential innate eye movement, the optokinetic reflex (OKR). We find that these corticofugal neurons are enriched in specific visual areas, and they prefer temporo-nasal visual motion, matching the direction bias of downstream NOT-DTN neurons. Remarkably, continuous OKR stimulation selectively enhances the activity of these temporo-nasally biased cortical neurons, which can efficiently promote OKR plasticity. Lastly, we demonstrate that silencing downstream NOT-DTN neurons, which project specifically to the inferior olive-a key structure in oculomotor plasticity, impairs the cortical modulation of OKR and OKR plasticity. Our results unveil a direction-selective cortico-brainstem pathway that adaptively modulates innate behaviors.