Efferent neurons control hearing sensitivity and protect hearing from noise through the regulation of gap junctions between cochlear supporting cells

It is critical for hearing that the descending cochlear efferent system provide a negative feedback to hair cells to regulate hearing sensitivity and provide the protection of hearing from noise. Here, we report that the medial olivocochlear (MOC) efferent nerves, which project to outer hair cells (OHCs), also could innervate OHC surrounding supporting cells (SCs) to regulate hearing sensitivity. MOC nerve fibers are cholinergic and acetylcholine (ACh) is a primary neurotransmitter. MOC nerve endings, presynaptic vesicular acetylcholine transporters (VAChT), and postsynaptic ACh receptors were visible in SCs and the SC area. Application of ACh in the SC could evoke a typical inward current, which reduced gap junctions (GJs) between SCs and consequently declined OHC electromotility, which is an active cochlear amplification and can increase hearing sensitivity. This indirect, GJ-mediated inhibition enhanced the direct inhibition of ACh on OHC electromotility but had long-lasting influence. In vivo experiments further demonstrated that deficiency of this GJ-mediated efferent pathway declined the regulation of active cochlear amplification and compromised the protection against noise. In particular, distortion production otoacoustic emission (DPOAE) showed a delayed reduction after noise exposure. Our findings reveal a new pathway for the MOC efferent system via innervating SCs to control active cochlear amplification and hearing sensitivity. These data also suggest that this GJ-mediated efferent pathway may play a critical role in the long-term efferent inhibition and is required for protecting hearing from noise trauma.

DIGESTIVE DISORDERS IN THE ORAL CAVITY

The progress made in fundamental medical research over the past decades, the scientific acquisitions in the field of genetics, molecular biology and biochemistry in relation to the explosive development of investigative technologies have revolutionized the clinical approach to many pathological entities, practically opening a new era in the evolution of clinical medicine. Dental medicine, as a science, feels the massive impact of the needs for knowledge and relaunches the interest of research in all its subspecialties. From this perspective, these are legitimized not only through the crisis in managing the immense volume of information, but also through the openings offered to the framework of conceptualizing and defining the identity of this branch of medicine, related to the need to particularize the specific problems in this discipline. Digestion is a fundamental process in the survival of an organism. It begins in the oral cavity, where the bolus is formed, and continues in the stomach, forming the chyme, which then reaches the small intestine and transforms into the chyle. Through mastication, the surface of food increases, thus the enzymes are able to act more easily on the substrate. The first enzymes to act on food are the salivary ones - salivary amylase, lingual lipase. Mastication is regulated through the contact of food with receptors in the oral cavity. These will send impulses by way of the trigeminal nerve towards the centre of mastication - located in the bolus. From the bolus, they will start the signals on the efferent pathway (trigeminal, hypoglossal and facial nerves) that will reach the masticatory muscles. Mechanical digestion (mastication) can thus begin. Mechanical digestion in the oral cavity results from mastication. During mastication, the food is manipulated by the tongue, crushed by the teeth and mixed with saliva. Concomitant with mechanical digestion, the chemical digestion takes place through the action of saliva. There are two types of salivary glands in the oral cavity: large glands - parotid, sublingual, submandibular and small glands - disseminated throughout the oral cavity. Within 24 hours, up to 1.5 liters of saliva are secreted, 99% of which is represented by water. The remaining 1% consists of enzymes, mucus, nitrogen content. After finalizing mastication, deglutition begins. This mechanical process consists of thrusting the bolus from the mouth towards the stomach, using the esophagus.

Bidirectional modulation of pain-related behaviors in the zona incerta

Central amygdala neurons expressing protein kinase C-delta (CeA-PKCδ) are sensitized following nerve injury and promote pain-related responses in mice. The neural circuits underlying modulation of pain-related behaviors by CeA-PKCδ neurons, however, remain unknown. In this study, we identified a functional monosynaptic inhibitory neural circuit that originates in CeA-PKCδ neurons and terminates in the ventral region of the zona incerta (ZI), a subthalamic structure previously linked to pain processing. Behavioral experiments further show that chemogenetic inhibition of GABAergic ZI neurons is sufficient to induce bilateral hypersensitivity in uninjured mice as well as contralateral hypersensitivity after nerve injury. In contrast, chemogenetic activation of GABAergic ZI neurons reverses nerve injury-induced hypersensitivity, demonstrating that silencing of the ZI is required for injury-induced behavioral hypersensitivity. Our results identify a previously unrecognized inhibitory efferent pathway from CeA-PKCδ neurons to the ZI and demonstrate that ZI-GABAergic neurons can bidirectionally modulate pain-related behaviors in mice.

Hypothalamic circuits for mechanically-evoked defensive attack

The innate defensive behaviors triggered by environmental threats play a critical role in animal survival. Among these behaviors, defensive attack physically toward threatening target (e.g. predator) is the last line of defense to struggle for survival. How the brain transforms threat-relevant sensory information into the action of defensive attack remains poorly understood. We found that noxious mechanical force in an inescapable context was a key stimulus to trigger defensive attack in laboratory mice. The mechanically-evoked defensive attack was abrogated by photoinhibition of vGAT+ neurons in the anterior hypothalamic nucleus (AHN). The AHN vGAT+ neurons encoded the intensity of mechanical force and were innervated by brain areas related to pain and attack. Activation of these neurons triggered biting attack toward predator, while suppressing other ongoing behaviors. The efferent pathway from AHN vGAT+ neurons to the periaqueductal gray was both sufficient and necessary for mechanically-evoked defensive attack. Together, these data revealed a GABAergic brain circuit engaged in converting noxious mechanical stimuli to neural signals that provoke defensive attack in mice.

Anti-inflammatory effects of sacral nerve stimulation: a novel spinal afferent and vagal efferent pathway

Sacral nerve stimulation (SNS) was reported to improve 2,4,6-trinitrobenzenesulfonic acid (TNBS)-induced colitis in rats. The aim of this study was to investigate whether the SNS anti-inflammatory effect is mediated via the local sacral splanchnic nerve or the spinal afferent-vagal efferent-colon pathway. Under general anesthesia, rats were administrated with TNBS intrarectally, and bipolar SNS electrodes were implanted unilaterally at S3. The sacral and vagal nerves were severed at different locations for the assessment of the neural pathway. SNS for 10 days improved colonic inflammation only in groups with intact afferent sacral nerve and vagus efferent nerve. SNS markedly increased acetylcholine and anti-inflammatory cytokines (IL-10) and decreased myeloperoxidase and proinflammatory cytokines (IL-2, IL-17A, and TNF-α) in colon tissues. SNS increased the number of c-fos-positive cells in the brain stem and normalized vagal activity measured by spectral analysis of heart rate variability. SNS exerts an anti-inflammatory effect on TNBS-induced colitis by enhancing vagal activity mediated mainly via the spinal afferent-brain stem-vagal efferent-colon pathway. NEW & NOTEWORTHY Our findings support that there is a possible sacral afferent-vagal efferent pathway that can transmit sacral nerve stimulation to the colon tissue. Sacral nerve stimulation can be carried out by spinal cord afferent to the brain stem and then by the vagal nerve (efferent) to the target organ.

Sacral nerve stimulation increases gastric accommodation in rats: a spinal afferent and vagal efferent pathway

Impaired gastric accommodation (GA) has been frequently reported in various gastrointestinal diseases. No standard treatment strategy is available for treating impaired GA. We explored the possible effect of sacral nerve stimulation (SNS) on GA and discovered a spinal afferent and vagal efferent mechanism in rats. Sprague-Dawley rats (450–500 g) with a chronically implanted gastric cannula and ECG electrodes were studied in a series of sessions to study: 1) the effects of SNS with different parameters on gastric tone, compliance, and accommodation using a barostat device; two sets of parameters were tested as follows: parameter 1) 5 Hz, 500 µs, 10 s on 90 s off; 90% motor threshold and parameter 2) same as parameter 1 but 25 Hz; 2) the involvement of spinal afferent pathway via detecting c-fos immunoreactive (IR) cells in the nucleus of the solitary tract (NTS) of the brain; 3) the involvement of vagal efferent activity via the spectral analysis of heart rate variability derived from the ECG; and 4) the nitrergic mechanism, Nω-nitro-l-arginine methyl ester (l-NAME), a nitric oxide synthase (NOS) inhibitor, was given before SNS at 5 Hz. Compared with sham-SNS: 1) SNS at 5 Hz inhibited gastric tone and increased gastric compliance and GA. No difference was noted between the stimulation frequencies of 5 and 25 Hz. 2) SNS increased the expression of c-fos in the NTS. 3) SNS increased cardiac vagal efferent activity and decreased the sympathovagal ratio. 4) l-NAME blocked the relaxation effect of SNS. In conclusion, SNS with certain parameters relaxes gastric fundus and improves gastric accommodation mediated via a spinal afferent and vagal efferent pathway. NEW & NOTEWORTHY Currently, there is no adequate medical therapy for impaired gastric accommodation, since medications that relax the fundus often impair antral peristalsis and thus further delay gastric emptying that is commonly seen in patients with functional dyspepsia or gastroparesis. The advantage of the potential sacral nerve stimulation therapy is that it improves gastric accommodation by enhancing vagal activity, and the enhanced vagal activity would lead to enhanced antral peristalsis rather than inhibiting it.