Various experimental approaches with electromyographic analysis of the activities of the intercostal muscles in acute or chronic preparations allow one to distinguish between those intercostal muscles mainly involved in respiratory function and those involved predominantly in postural function. Modifications of the spontaneous electrical activity of diverse respiratory muscles during these various experimental conditions can lead to a fairly general understanding of the neural mechanisms involved. The rigidity of decerebration is evident in the intercostal muscles by the appearance of tonic electromyographic activity. The intercostal muscles are composed of functional slow and fast motor units. The range of the motor units' contractile and fatigue properties influence the nervous system's control of the intercostal muscles in response to various ventilatory and nonventilatory requirements. The localization and morphology of intercostal motoneurons in adult cats were examined by retrograde labeling with horseradish peroxidase after intramuscular or intracellular injections of the tracer.

Recent in vitro studies using brain slices or an isolated preparation of brainstem and spinal cord have confirmed that serotoninergic mechanisms are involved in the central nervous control of breathing. For example, increases in respiratory frequency, via activation of 5-HT1 receptors, have been elicited either by the use of exogenous 5-HT 1 or via the release of endogenous 5-HT after stimulation of the raphe nuclei2. Other workers have reported a biphasic effect of 5-HT on respiratory rate, an initial increase in inspiratory frequency (Fi) being followed by a low-frequency phase despite the continued presence of 5-HT 3,4. Interestingly, the effect of 5-HT on the respiratory rhythm in vitro appears to depend on the baseline respiratory rate4, the inhibitory effect being more pronounced in a preparation with a higher respiratory rate.

Extracellular recordings were made in the dorsal respiratory group (DRG) and adjacent reticular formation following single-shock stimulation of the anterior ethmoidal nerve (AEN) and during sneeze evoked by repetitive stimulation of the AEN in nembutal-anaesthetized, curarized and ventilated cats. These neurones were characterised according to (i) their activity during the respiratory cycle (as inspiratory augmenting or decrementing (I Aug or I Dec), expiratory augmenting or decrementing (E Aug or E Dec), silent or tonic), and (ii) their axonal projection (bulbospinal or non-bulbospinal-non-vagal (BS or NBS-NV)). Following single-shock stimulation of the AEN, most of the inspiratory neurones were transiently inhibited, whereas E Aug neurones were activated and E Dec neurones were activated and then inhibited. Silent neurones responded with a multispike or a paucispike pattern. Following repetitive stimulation of the AEN and during the resulting sneeze reflex, I Aug neurones increased their activity in parallel with the phrenic activity, I Dec neurones fired at the onset and at the end of the inspiration, E Dec and some silent neurones fired either during the compressive phase or after the expulsive phase, whereas E Aug and some silent neurones fired during the expulsive phase. We conclude that sneeze involves a reconfiguration of the central respiratory drive which uses, at least partly, the respiratory network to trigger a non-ventilatory defensive motor act.

Studies of endoepithelial-triggered reflexes, such as nasal respiratory reflexes, are difficult to carry out in humans without a non-traumatic and reliable stimulation device. The air puff stimulator described allows us to deliver air puffs of brief duration at various intensities, frequencies, and temperatures. The stimulation is non-traumatizing and non-nociceptive. We have successfully used it in animals as a source of specific stimuli to enable us to study central and peripheral neuronal responses evoked by activation of endonasal dynamically sensitive receptors. Immunohistochemical studies of the c-fos expression evoked during sneezing elicited by air puffs provided additional evidence for the specificity of this particular stimulation technique. We suggest that the use of such a non-traumatizing air puff stimulator could be extended to human studies. It might be particularly useful in developmental studies of endoepithelial-triggered reflexes such as those respiratory reflexes whose immaturity at birth can be life-threatening.

We studied the activity of 50 slow-adapting receptors (SAR), 13 rapidly-adapting receptors (RAR) and 3 expiratory modulated receptors in the different phases of sneeze in tracheostomized and non-tracheostomized anaesthetized cats. SAR activity increased progressively during the first phase of the preparatory inspiration in parallel to integrated diaphragmatic activity. During the second phase of the preparatory inspiration, SAR increased their discharge frequency; higher threshold SAR and RAR were recruited. During the compressive phase, discharge of SAR kept stable or increased slightly in parallel to an increase in transpulmonary pressure, while expiratory modulated receptors were activated. During the expulsive phase, only RAR were activated. Increase in transpulmonary pressure at the end of the inspiratory phase of sneeze shortened expiratory duration and increased the rate of rise of expiratory muscle activity. Increase in transpulmonary pressure at the end of the compressive phase further shortened expiratory duration. These results suggest: first, a facilitatory effect on the triggering of the second phase of the preparatory inspiration from SAR; second, a modulation of the early stage of expiration by SAR, RAR and expiratory modulated receptors during the compressive phase; third, a permissive effect on a rapid expulsive thrust by SAR which can be further limited by RAR; fourth, a facilitatory effect on the triggering of inspiratory activity that follows the expiratory thrust by RAR. Both SAR and RAR might participate in the occurrence of successive sneeze in an attack and in the increased frequency of sneezing. Our results suggest that complex convergent inputs from nasal and vagal receptors, which alter the respiratory rhythm and rhythmogenesis, modulate finely the sneeze reflex.

État des connaissances sur la sarcoïdose du système nerveux central.Une localisation dans le système nerveux central est observée dans 5 à 16% des cas de sarcoïdose. Les manifestations cliniques neurologiques sont variées: épilepsie, troubles cognitifs ou psychiques, manifestations hypothalamohypophysaires, tableaux focaux d'allure pseudotumorale, hydrocéphalie, association très fréquente d'une méningite aseptique lymphocytaire, latente et avec une fréquence variable de l'atteinte de nerfs crâniens, en particulier le nerf VII. L'atteinte du système nerveux central est le plus souvent précoce et révélatrice et s'intègre quasi constamment dans le cadre d'une sarcoïdose systémique typique, d'emblée évidente ou plus rarement différée. L'atteinte isolée du système nerveux central reste exceptionnelle. Le diagnostic repose principalement sur deux arguments: la confirmation du diagnostic de sarcoïdose systémique et la compatibilité clinique et paraclinique (notamment en IRM) des anomalies neurologiques. Une confirmation histopathologique neurologique est rarement nécessaire et/ou possible. Un traitement corticoïde général est nécessaire dans toutes les formes symptomatiques et permet le plus souvent une réponse clinique et une régression des lésions actives identifiées en imagerie, avec une amélioration clinique plus ou moins complète. Le traitement est le plus souvent prolongé sur plusieurs années, la posologie étant guidée sur l'évolution clinique et en imagerie qui permettent de déterminer la dose seuil nécessaire. L'atteinte du système nerveux central demeure une localisation potentiellement grave de la sarcoïdose avec une mortalité et une morbidité non négligeables. La prise en charge évolutive doit être rigoureuse pour limiter les risques iatrogènes en fonction des enjeux thérapeutiques.Des études multicentriques sont nécessaires pour préciser les facteurs intervenant dans l'incidence, la présentation et le pronostic à distance sous traitement de la sarcoïdose du système nerveux central. La place des traitements épargnant en corticostéroïdes doit être précisée.Current knowledge on central nervous system sarcoidosis.Sarcoidosis is localized in the central nervous system in 5 to 16% of the cases. Various neurological manifestations are observed, inluding: seizures, cognitive or psychic manifestations, hypothalamic and pituitary involvement, local pseudotumors, and hydrocephalus very frequently associated with asymptomatic lymphocytic meningitis and with cranial nerve palsy, particularly palsy of the seventh nerve, occurring less regurlarly. CNS localization is most often an early manifestation of the disease, unmasking sarcoidosis. It is often part of primary or secondary systemic polyvisceral sarcoidosis. The diagnosis is mainly based on two arguments: confirmation of the existence of systemic sarcoidosis and clinical and paraclinical compatibility of neurological abnormalities (particularly at magnetic resonance imaging [MRI]). Neurological histopathology is rarely necessary to confirm the diagnosis. Corticotherapy is indicated in all symptomatic cases and most often leads to a more or less complete clinical response evidenced by regression of active lesions identified on MRI. The treatment must often be prolonged for several years, and clinical and MRI evolution help guide therapeutical choices for dosages and threshold doses. CNS involvement is potentially severe with mortality and morbidity rates that are not insignificant. Limiting of iatrogenic risks requires adequate follow-up .Multicenter studies are necessary to determine factors influencing the incidence and long-term prognosis of CNS sarcoidosis treated with corticotherapy. The efficacy of treatments other than corticotherapy must be evaluated.

The aim of this work was to study the nonvagal mechanisms which might induce apneic reflexes in kittens. Experiments were performed on spontaneously breathing animals (19 kittens at different postnatal ages). Animals were anesthetized (halothane) or decerebrated by transcollicular section of the brainstem. Weakly nociceptive cutaneous stimulations and various oral stimulations were administered in all animals. In 10 kittens, one of the lingual nerves was stimulated electrically. In 3 decerebrate kittens the effects of serotonin on respiratory activity and on muscles innervated by the hypoglossal nerve were studied. All the stimulations produced apneas of variable duration, and expiratory reinforcement was associated with activation of pretracheal muscles. Similar effects were observed after applying serotonin to the floor of the 4th ventricle. Thus serotonin may be involved in the mechanisms that cause some apneas.

We studied the effects of bilateral vagotomy and step pulmonary inflations (5, 10, 15 mmHg, i.e., 0.66, 1.33, 2 kKPa) on sneeze reflex in ketamine-anaesthetized cats. Bilateral vagotomy lengthens the duration of preparatory inspiration and diminishes the amplitude of expiratory activities in sneeze. In contrast, 5 mmHg pulmonary inflation facilitates the sneeze. It shortens the inspiratory preparation and increases the frequency of sneeze attacks. At 10 mmHg pulmonary inflations, inspiration is inhibited and only expiratory thrust occurs. At 15 mmHg pulmonary inflations, vagal afferent stimulations inhibit the sneeze.

The aim of the present work was to study oral trigeminal mechanisms which might induce apnoeic reflexes in adult cats and kittens at different postnatal ages. Various oral stimulations and electrical stimulations of the lingual nerve produced apnoeas whose duration decreased with age until three weeks of life. In addition, swallowing was only rarely observed before 5 days and then occurred with apnoea until the third week. Responses became similar to those observed in adults between weeks 3 and 4. Thus, in kittens, the nervous control which regulates coordination between breathing and swallowing appears to be immature at birth.

Neurons supplying the nasal mucosa in the cat were retrogradely labelled with horseradish peroxidase. Sensory trigeminal neurons to the inferior and superior nasal meati are somatotopically organized, according to the ophthalmic or maxillary origin of the afferents studied. Whatever their relative location, the cell bodies from nasal afferents were, on average, smaller than the overall cell population in the ganglion, in keeping with the high proportion of nasal receptors innervated by thin fibers. Postganglionic neurons from parasympathetic origin could be labelled in the sphenopalatine ganglion. These neurons probably supply mucosal secretory glands. They are in the same size range as the bulk of neurons in the same ganglia.

The aim of this study was to precise the role of the different trigeminal nerve branches involved in innervation of the nostril in triggering the sneeze reflex. Electrical stimulation of the anterior ethmoidal, posterior nasal and infraorbital nerves was performed in anaesthetized cats. Stimulation of these 3 nerves produced sneezing identical to that induced by mechanical stimulation. Our results emphasize inhibition of the sneeze reflex related to stimulation of the anterior ethmoidal or the posterior nasal nerves by stimulation of the infraorbital nerve.

In twenty adult cats of either sex under nembutal anaesthesia, we aimed at delineating the sensitive territory of trigeminal nerves innervating the nasal mucosa. The different trigeminal nerves (anterior ethmoidal, posterior nasal and infraorbital nerves) were dissected in the orbit. Activity of these nerves was recorded during spontaneous nasal and tracheal breathing and in response to various stimuli: mechanical (manual probing and air jets) and irritants (ammonia vapours). Multiple and unitary activity recorded in nerve filaments enabled a classification of the receptors on the basis of their discharge pattern as rapidly-, intermediately- or slowly adapting receptors, and as drive or non-drive nasal receptors depending on whether or not the respiratory modulation was preserved during tracheal breathing.

During feline postnatal development, the size of phrenic afferent neurons labelled by horseradish peroxidase was evaluated in comparison to that of the bulk of counterstained neurons located in the same cervical dorsal root ganglia (DRG) (C5-C6). From age 1 week to maturity, small and large cell components were individualized from experimental size distributions using a mathematical approach. The analysis of data in adult indicated a close correspondence between small cells and unmyelinated afferents and between large cells and myelinated afferents, respectively. From age 1 week to adulthood, mean increases in cell diameter ranged between 10 microns (small cells from phrenic afferents) and 29.5 microns (large counterstained cells). In each population, the ratio of small/large cells remained constant during growth. In contrast to data in adults, at 1 week, large phrenic neurons were bigger than the counterstained ones. At 19 weeks, the cat DRG cells had not yet reached their adult size.

Sizes of neuronal somata in the cat cervical dorsal root ganglia were determined at different levels (C1-C8). The average value and class distribution of mean cell diameter were analyzed. The ganglia from C1 to C5 could be clearly distinguished from those at levels of brachial plexus afferents (C6-C8) with respect to cell size range, distribution and average. The size distribution, most often limited to 70 microns from C1 to C5, skewed to more than 90 microns from C6 to C8. Cells in the 35-50 microns range of diameter constituted the main portion of the cell population (49-52%) at the C1-C5 levels, whereas from C6 to C8 51-77% of the ganglion cell bodies were more than 50 microns in diameter. The cell size distribution of afferents projecting from C1 to C5 and supplying different muscle or cutaneous targets was studied following retrograde labeling with horseradish peroxidase conjugated to wheatgerm agglutinin. Sizes of cell bodies of biventer cervicis (postural muscle), phrenic (purely respiratory muscle) and cutaneous afferents were all similar. The labelled cell bodies were in the majority (51-64%) less than 35 microns in diameter and ranged towards smaller diameters than counterstained cells in the corresponding ganglia. In spite of similarities in cell size distribution it was estimated from the fiber caliber spectra of the labelled afferents that both unmyelinated and myelinated cutaneous afferents originate from larger cell bodies than muscle afferents in the same diameter range.

The conduction velocities of motor, IA and non-nociceptive cutaneous sensory fibres have been studied in the ulnar and median nerves of 145 healthy fullterm neonates and in 77 preterm neonates (postconceptional age-range 28 to 42 weeks). The posterior tibial-nerve motor and IA fibres were studied: the sural nerve cutaneous-fibre conduction velocities were measured in fullterm neonates only. At each age the IA fibre conduction velocities were the highest. There was no difference between the conduction velocity increase per week of postconceptional age in motor and cutaneous fibres. Except for the cutaneous-nerve fibres, conduction velocities were higher in the upper than in the lower limbs.

The sizes of neuronal somata in cat dorsal root ganglia were determined at the different thoracic segmental levels (T1–T13). The intersegmental variations in the average value and class distribution of diameters were analysed. The maximal and minimal average mean cell diameters were 51.1 and 43.3 μm at the T1 and T2 levels, respectively. Caudally, this value gradually increased from T2 to T8 (47.8 μm) and thereafter decreased progressively to T12 (44.7 μm). At T1, large cells (> 50 μm in diameter) were 3.3-fold in excess compared to small ones (< 35 μm in diameter). The proportion of large to small cells strongly decreased to a 0.9 ratio from T1 to T2, then increased again from T2 (0.9) to T8 (2.3). The size distributions of the overall cell populations were compared to those of neurones supplying muscular targets via the external intercostal nerves or cutaneous targets via the lateral branch of the internal intercostal nerves, identified following the retrograde transport of horseradish peroxidase. The size distribution of cells serving cutaneous nerves was similar to that exhibited by the overall population of ganglion cells. In contrast, the size distributions of cells giving rise to muscle afferents tended towards smaller values. In the thoracic dorsal root ganglia, the cell body sizes of the muscular primary afferents were close to those previously reported for the visceral primary afferents.

In decerebrate, C2-spinalized cats, stimulation of the C6-phrenic root produces a weak activation of phrenic motoneurons in the adjacent C5 segment in a few animals (23%). When phrenic motoneurons are electrically excited by testing stimulation applied to the spinal cord or internal intercostal nerve, the evoked responses recorded in a cervical phrenic root are partly inhibited by conditioning stimulation applied to another ipsilateral or contralateral cervical phrenic root. We therefore conclude that phrenic fibers exert both inhibitory and excitatory effects on adjacent phrenic motoneurons in the cervical spinal cord.

Conduction velocities of non-nociceptive cutaneous and IA afferent fibres and alpha-motor fibres from ulnar, median, deep peroneal, posterior tibial and sural nerves have been measured in healthy full-term newborns, using surface electrodes. There is an overlapping in the distribution of the individual values of conduction velocities for the different types of fibres. The conduction velocities of cutaneous afferent fibres are not different in the upper or lower limbs. The conduction velocities of motor and IA fibres are higher in the upper than in the lower limb. In the upper limb, conduction velocities of IA fibres are higher than those of motor fibres, as they are in the lower limb for the posterior tibial nerve. Moreover, conduction velocities of motor fibres do not differ in males and females.

The percutaneous stimulation of both the motor cortex and the spinal cord have been used to study the central motor pathways of 19 healthy full-term newborns and of 5 infants (17 months to 4 years). The responses of lower limb muscles to cortical stimulation were more difficult to obtain than those of upper limb muscles. Conduction velocities of central motor fibres along the spinal cord (between C7 to L4) were around 10 m/s in full-term newborns and 38 m/s at the age of 4 years old. These values are considerably less than those published in adult man (48 to 60 m/s).