Microinjections of beta-noradrenergic substances in the cerebellar vermis of decerebrate cats modify the gain of the vestibulospinal reflexes.

1. The noradrenergic (NA) afferent system, which originates mainly from the locus coeruleus and projects to the cerebellar cortex, may act on the corresponding neurons by utilizing not only alpha- but also beta-adrenoceptors. Since the vermal cortex of the cerebellar anterior lobe receives a labyrinth input and projects to the lateral vestibular nucleus (LVN), experiments were performed in precollicular decerebrate cats to find out whether the noradrenergic system intervenes in the control of posture as well as of the dynamic characteristics of vestibulospinal (VS) reflexes elicited by recording the multiunit EMG responses of the forelimb extensor triceps brachii of both sides to roll tilt of the animal at 0.15 Hz, +/- 10 degrees. In particular, we used the method of local microinjection into the vermal cortex of the cerebellar anterior lobe of the non-selective beta-adrenergic agonist ((+/-) -isoproterenol hydrochloride) or antagonist (dl-propranolol hydrochloride) to act on both beta 1- and beta 2-adrenoceptors. 2. Unilateral injection into the vermal cortex of the culmen of isoproterenol (0.25-0.50 microliters at the concentration of 8-16 micrograms/microliter of saline stained with pontamine 5%) decreased the extensor tonus in the ipsilateral forelimb, while the postural activity either remained unmodified or slightly increased in the contralateral fore-limb. The same injection significantly increased the gain (imp./sec/deg) of the first harmonic component of the EMG responses of the ipsilateral and to a lesser extent also of the contralateral triceps brachii to animal tilt. This effect was also associated with slight changes in the phase angle of the responses, which remained positional throughout the experiments. The effects described above occurred within 5-10 min after the injection and reached the highest values after 20-30 min; they were then followed for about 2 hours after the injection, before disappearing. 3. In contrast to these findings, injection in other experiments of 0.25-0.50 microliter of a solution of propranolol at the concentration of 16 micrograms/microliter of saline increased the extensor tonus in the ipsilateral limbs, while the decerebrate rigidity either remained unmodified or slightly decreased in the contralateral limbs. In addition, the amplitude of modulation and thus the response gain of the ipsilateral triceps brachii to the same parameters of animal tilt decreased. This effect was associated with slight changes in the phase angle of the responses. There was also a slight but insignificant decrease in gain of the responses recorded contralaterally to the side of the propranolol injection.(ABSTRACT TRUNCATED AT 400 WORDS)     

Microinjections of alpha 1- and alpha 2-noradrenergic substances in the cerebellar vermis of decerebrate cats affect the gain of the vestibulospinal reflexes.

1. In addition to mossy and climbing fibers, the Purkinje (P)-cells of the cerebellar cortex receive noradrenergic (NA) afferents which originate mainly from the locus coeruleus. Since these fibers impinge also on the vermal cortex of the cerebellar anterior lobe, which receives a labyrinth input and projects to the lateral vestibular nucleus, experiments were performed in precollicular decerebrate cats to find out whether unilateral injection of alpha-adrenergic substances into the vermal cortex of the cerebellar anterior lobe exerted some influence on posture as well as on the dynamic characteristics of vestibulospinal (VS) reflexes evaluated by recording the multiunit EMG responses of the forelimb extensor triceps brachii of both sides to roll tilt of the animal at 0.15 Hz, +/- 10 degrees. 2. Unilateral injection into the vermal cortex of the culmen of the alpha 1-adrenergic agonist metoxamine or the alpha 2-adrenergic agonist clonidine (0.25 microliters at the concentration of 4 micrograms/microliters of saline) produced a postural asymmetry, characterized mainly by a slight decrease of the extensor tonus in the ipsilateral forelimb and an increased tonus in the contralateral forelimb. The same substances significantly increased the gain (imp./sec/deg) of the first harmonic component of the EMG responses of the ipsilateral and the contralateral triceps brachii to animal tilt. The crossed effects were more prominent for the alpha 2- than for the alpha 1-agonist. However, no significant changes in the phase angle of the responses were observed in both instances. The effects described above occurred within 5-10 min after the injection, reached the peak values after 15-20 min, and disappeared within 2 hours. 3. The postural and reflex changes described above were not due to irritative events following the injection, since they were not observed in control experiments after injection of 0.25 microliter of saline into the same corticocerebellar area prior to the administration of the alpha 1- or the alpha 2-adrenergic agonist. Moreover, the resulting effect were dose-dependent. 4. Both the ipsilateral as well as the contralateral effects induced by the alpha 1- or the alpha 2-adrenergic agonist metoxamine or clonidine were impaired by previous injection into the same corticocerebellar area of the corresponding alpha 1- or alpha 2-adrenergic antagonist prazosin or yohimbine, respectively (0.25 microliter at the concentration of 8-16 micrograms/microliters in both cases).(ABSTRACT TRUNCATED AT 400 WORDS)     

Injections of beta-adrenergic substances in the locus coeruleus affect the gain of vestibulospinal reflexes in decerebrate cats

1. The tonic discharge of the noradrenergic locus coeruleus (LC) neurons is dampened by norepinephrine (NE) which acts not only on alpha2-adrenoceptors located on the somatodendritic membrane, through mechanisms of recurrent inhibition, but also on beta-receptors. Experiments were performed to find out whether inactivation of LC neurons by local injection of the beta-adrenergic agonist isoproterenol into the LC complex of one side produced changes in posture as well as in the gain of vestibulospinal reflexes acting on forelimb extensors. 2. In precollicular decerebrate cats the amplitude of modulation and thus the gain of the multiunit EMG responses of the forelimb extensor triceps brachii to animal tilt at 0.15 Hz, +/- 10 degrees, leading to sinusoidal stimulation of labyrinth receptors, were quite small. Microinjection of 0.25 microliter of a solution of the beta-adrenergic agonist isoproterenol at the concentration of 4.5-9.0 microgram/microliter of sterile saline into the LC complex of one side decreased the extensor rigidity in the ipsilateral limbs and to a lesser response gain of the ipsilateral triceps brachii to the same parameters of labyrinth stimulation greatly increased (t-test, P less than 0.001); moreover, a slight but significant increase in phase lead of the responses was observed. These findings appeared within 5-10 min after the injection of isoproterenol, fully developed within 20-30 min and persisted for about 2-3 hours after the injection. 3. The increased gain of the vestibulospinal reflexes acting on the triceps brachii did not depend on the decreased postural activity following injection of the beta-adrenergic agonist, since it was still observed if the reduced EMG activity of the extensor muscle following the injection was compensated for by an increased static stretch of the muscle. The positive correlation (t-test, P less than 0.001) between gain of the multiunit EMG response of the triceps brachii to animal tilt and base frequency observed in the control experiment disappeared and was substituted by a slight negative correlation (t-test, P less than 0.05) after injection of isoproterenol into the LC complex, probably due to a more prominent recruitment of motor units for low level of background discharge of the muscle. 4. In addition to the effects which involved the triceps brachii ipsilateral to the side of the injection, a smaller but significant increase in response gain affected the contralateral extensor muscle. This increase in gain was also associated with a slight increase in phase lead of the responses.(ABSTRACT TRUNCATED AT 400 WORDS)     

Effects of microinjection of vasopressin in dorsal pontine reticular structures on the gain of vestibulospinal reflexes in decerebrate cats.

1. The possibility that vasopressin (VP) acts on the dorsal pontine reticular formation (pRF) and the related medullary inhibitory reticulospinal (RS) system to control posture as well as the vestibulospinal reflexes has been investigated by injecting small doses of VP in precollicular decerebrate cats. 2. Unilateral microinjection of VP (0.25 microliters at the concentration of 10(-11) micrograms/microliters saline) in the pRF decreased the extensor rigidity in the ipsilateral limbs, while that of the contralateral limbs either decreased or increased. The same injection also produced a moderate or a prominent increase in gain of the multiunit EMG responses of the ipsilateral triceps brachii to roll tilt of the animal (t-test, P less than 0.001 for either group of responses). In the first instance the response gain of the contralateral triceps brachii to animal tilt slightly increased, while the pattern of response remained always of the alpha-type, as shown for the ipsilateral responses (increased EMG activity during ipsilateral tilt and decreased activity during contralateral tilt). In the second instance, however, the response gain showed only slight changes, while the pattern of responses reversed from the alpha- to the beta-type. These findings occurred 5-20 min after the injection, fully developed within 30-60 min and disappeared in about 2-3 hours. 3. The structures responsible for the postural and reflex changes described above were located in the dorsal pontine tegmental region immediately ventral to the LC, and included the peri-LC alpha and the surrounding dorsal pRF. The induced effects depended upon the injected neuropeptide, since previous injection of an equal volume of saline stained by the pontamine sky blue dye into the same dorsal pontine area was ineffective. 4. We postulated that VP exerts an excitatory influence on ipsilateral dorsal pRF neurons. The increased discharge of these neurons and the related medullary inhibitory RS neurons would lead to a decreased postural activity in the ipsilateral limbs. However, since these inhibitory RS neurons fire out of phase with respect to the excitatory vestibulospinal neurons, it appears that the higher the firing rate of the RS neurons in the animal at rest, the greater the disinhibition that affects the limb extensor motoneurons during ipsilateral tilt. These motoneurons would then respond more efficiently to the same excitatory volleys elicited by given parameters of stimulation, thus leading to an increased gain of the EMG responses.(ABSTRACT TRUNCATED AT 400 WORDS)     

Injections of a beta-adrenergic antagonist in pontine reticular structures modify the gain of vestibulospinal reflexes in decerebrate cats

1. The norepinephrine (NE)-containing locus coeruleus (LC) neurons control posture as well as the gain of the vestibulospinal reflexes either through direct coeruleospinal (CS) projections or by inhibiting the dorsal pontine reticular formation (pRF) and the related medullary inhibitory reticulospinal (RS) system. The question whether these inhibitory influences on the pRF are mediated through beta-adrenoceptors was investigated by injecting in precollicular decerebrate cats small doses of the non-selective beta-adrenergic antagonist propranolol in different pontine tegmental structures. 2. Injection of propranolol (usually 0.25 microliters at the concentration of 4.5 micrograms/microliters of saline) in dorsal pontine structures, which decreased the tonic contraction of limb extensors ipsilateral to the side of the injection, greatly increased the amplitude of the multiunit EMG responses of the ipsilateral triceps brachii to roll tilt of the animal at 0.15 Hz, +/- 10 degrees. Correspondingly, the response gain of the forelimb extensor to labyrinth stimulation increased. Moreover, a slight decrease in phase lead of the responses was observed. These responses were always characterized by an increased EMG activity during ipsilateral tilt and a decreased activity during contralateral tilt, as shown in the control records (alpha-responses). The same injection also produced in some instances an increase of the extensor tonus of the contralateral limbs, associated with an increased EMG activity of the contralateral triceps brachii; on the other hand, the amplitude of modulation and thus the response gain of this muscle to the same parameters of labyrinth stimulation decreased, while the response pattern reversed (beta-responses), thus being opposite to that displayed by the triceps brachii ipsilateral to the side of the injection. 3. The changes in posture and reflexes described above appeared 10-20 min after unilateral injection of propranolol in the pRF, reached in highest values in about 60-100 min and persisted for more that three hours before returning to the control level. These effects were not due to irritative phenomena following injection of the fluid, since neither changes in posture nor in the response gain of the triceps brachii to labyrinth stimulation were observed after injection of an equal volume of saline in the pRF of that side. Moreover, the magnitude of the effects increased to some extent in relation to the dose of the beta-adrenergic blocker. 4. Histological controls indicated that the structure responsible for these postural and reflex changes was located in the dorsal pontine tegmental region immediately ventral to the LC and included the peri-LC alpha and the surrounding dorsal pRF.(ABSTRACT TRUNCATED AT 400 WORDS)     

Effects of microinjection of cholinergic agonists into the pontine reticular formation on the gain of vestibulospinal reflexes in decerebrate cats

1. The question of which pontine neuronal groups and related receptors can mediate the cholinergic induction of the increased gain of vestibulospinal reflexes elicited by sinusoidal stimulation of labyrinth receptors was investigated by injecting in precollicular decerebrate cats either carbachol, which is a mixed muscarinic-nicotinic agonist, or bethanechol, which is a pure muscarinic agonist, via a cannula stereotaxically oriented in different pontine tegmental structures. 2. Injection of 0.1-0.2 microliter of carbachol solution (0.01-0.2 microgram/microliter of sterile saline) into the dorsal aspect of the pontine reticular formation (pRF), which slightly decreased the tonic contraction of limb extensors ipsilateral to the side of the injection, greatly increased the amplitude of the multiunit EMG response of the ipsilateral triceps brachii to roll tilt of the animal at 0.15 Hz, +/- 10 degrees, leading to selective stimulation of labyrinth receptors. Correspondingly, the response gain of the forelimb extensor to labyrinth stimulation increased. Moreover, a slight decrease in phase lead of the responses was observed. These findings were not attributable to decreased postural activity, since they were still observed when postural EMG activity was reflexly maintained by an increased static stretch of the muscle. No changes in the dynamic characteristics of the responses were observed in the contralateral triceps brachii. 3. The changes in posture as well as in response gain produced by the carbachol injection appeared suddenly, but partially declined to reach a plateau level which persisted for several hours before returning to the control level. Moreover, the magnitude of the effects increased in relation to the dose of the cholinergic agonist. 4. Histological controls indicated that the structure responsible for these postural and reflex changes was located in the dorsal aspect of the pontine tegmentum immediately ventral to the principal locus coeruleus (LC); this area corresponds to the peri-LC region and the surrounding pRF including the dorsal aspect of the central tegmental field. The effects were still obtained after chronic kainic acid lesioning of the gigantocellular area of the medulla. 5. An increase in gain of the vestibulospinal reflex which was as potent, dose-dependent, and site-specific as that previously observed with carbachol, appeared after injection of the pure muscarinic agonist bethanechol.(ABSTRACT TRUNCATED AT 400 WORDS)     

Effects of microinjection of a cholinergic agonist into the locus coeruleus on the gain of vestibulospinal reflexes in decerebrate cats

1. Experiments were performed in precollicular decerebrate cats to determine whether activation of locus coeruleus (LC) neurons elicited by local injection of the cholinergic agonist carbachol modifies the dynamic characteristics of responses of forelimb extensors to selective stimulation of labyrinth receptors resulting from roll tilt of the animal. 2. Injection of 0.1-0.4 microliter (usually 0.25 microliter) of carbachol at a concentration of 0.02-0.1 micrograms/microliter of sterile saline into the LC of one side, which slightly increased the tonic contraction of limb extensors ipsilateral to the side of the injection, greatly decreased the amplitude of the multiunit EMG response of the ipsilateral triceps brachii to animal tilt at 0.15 Hz, +/- 10 degrees. Correspondingly, the response gain of this forelimb extensor decreased. Moreover, a significant increase in phase lag of the responses was observed. These findings did not result from the increased postural activity, since they were still observed when the limb position was adjusted so that the spontaneous EMG activity remained constant throughout the experiments. 3. The changes in posture as well as in response characteristics of the forelimb extensor to labyrinth stimulation produced by carbachol injection appeared a few min after the injection and soon reached a plateau level which persisted for several hours before returning to the control levels. 4. The effects described above involved mainly, if not exclusively, the limbs ipsilateral to the side of the injection. However, the effects of local injection into the LC of one side could be reproduced on the contralateral side following injection into the LC of that side. 5. The increase in phase lag of the multiunit EMG responses of the triceps brachii to labyrinth stimulation appeared at a threshold lower than that required to decrease the response gain of this extensor muscle. These findings suggest that different neuronal populations within the LC complex, one projecting directly to the spinal cord, the other projecting indirectly through the pontine reticular formation, are involved in the control of phase angle and gain of the vestibulospinal reflexes, respectively. However, as soon as the threshold was reached the effects described above were dose-dependent. 6. Histological controls indicated that the structure responsible for the postural and reflex changes described above corresponded to the LC. In fact, postural and reflex changes opposite in sign to those described above were obtained when the same amount of carbachol was injected into the dorsal aspect of the pontine reticular formation (pRF) located immediately ventral to the LC.(ABSTRACT TRUNCATED AT 400 WORDS)     

Pontine reticular origin of cholinergic excitatory afferents to the locus coeruleus controlling the gain of vestibulospinal and cervicospinal reflexes in decerebrate cats

1. Previous experiments had shown that the medullary inhibitory reticulospinal (mRS) neurons act 180 degrees out-of-phase with respect to the excitatory vestibulospinal (VS) neurons during the vestibular and the neck reflexes involving the limb extensor motoneurons. This finding suggested that the higher the firing rate of the medullary inhibitory RS neurons in the animal at rest, the greater the disinhibition which affects the limb extensor motoneurons during side-down roll tilt of the animal or side-up neck rotation, thus leading to an increased gain of response of limb extensors to sinusoidal stimulation of labyrinth and neck receptors. The gain of these postural reflexes would then represent a sensitive test to evaluate the background discharge of the inhibitory reticulospinal system of the medulla. 2. The discharge of the inhibitory mRS neurons is under the tonic excitatory control of cholinergic pontine reticular formation (pRF) neurons which are also self-excitatory, while these cholinergic pontine neurons are in turn inhibited by the norepinephrine (NE)-containing locus coeruleus (LC) neurons, which are also self-inhibitory due to mechanisms of recurrent and/or lateral inhibition. The present experiments were performed to find out whether cholinergic and cholinoceptive pontine reticular neurons, which are under the inhibitory control of the LC neurons, also send axons to the LC on which they may exert an excitatory influence. This excitatory effect would then counteract the self-inhibitory influence mediated by the NE, which acts on the alpha 2-adrenoceptors distributed on the somatodendritic membrane of the LC neurons. 3. In precollicular decerebrate cats, local injection into the dorsal aspect of the pontine tegmentum of 0.25 microliter of a solution of the muscarinic blocker atropine sulphate at the concentration of 6 micrograms/microliter of sterile saline did neither modify the postural activity in the ipsilateral limbs nor the response gain of the ipsilateral forelimb extensor triceps brachii to sinusoidal stimulation of labyrinth receptors (roll tilt of the animal at 0.15 Hz, +/- 10 degrees). These negative results were attributed to the fact that in these preparations the activity of the cholinergic and cholinoceptive pRF neurons and the related inhibitory mRS neurons is very low, due to the tonic discharge of the NE-containing LC neurons, which exert a prominent inhibitory influence on the underlying reticular structures.(ABSTRACT TRUNCATED AT 400 WORDS)     

Contribution of the cerebellar anterior vermis to the gain and spatiotemporal properties of the vestibulospinal reflex: a behavioural and cellular analysis

Functional inactivation of the lobules IV-V of the cerebellar vermis obtained by local microinjection of the GABA-A agonist muscimol, depresses, in decerebrate cats, the amplitude of the VS reflex recorded from the forelimb extensor TB and may occasionally affect its spatial and/or temporal properties. The activity changes induced by tilting the animal head in all the possible directions were uniformely reduced. Experiments of unit recording from the same region submitted in other experiments to the drug injection, revealed that a large proportion of P-cells (67%) showed spatially tuned responses to the labyrinth input, characterized by preferred directions which were uniformely scattered over the horizontal plane. Neurons with opposite orientations could be found within a relatively narrow volume of corticocerebellar tissue, that could have been easily inactivated by injected volumes (0.25 microliter, 8 micrograms/microliter) of muscimol. We proposed that the spatial tuning of the P-cell responses to the labyrinth input is a basic property which allows the cerebellum to control the gain of VS reflexes elicited by head tilts in a broad directional range.     

Inhibition of vestibulospinal reflexes during the episodes of postural atonia induced by unilateral lesion of the locus coeruleus in the decerebrate cat

1. The spontaneous EMG activity of the forelimb extensor triceps brachii of both sides as well as their responses to roll tilt of the animal at 0.15 Hz, +/- 10 degrees leading to sinusoidal stimulation of labyrinth receptors were tested in precollicular decerebrate cats, before and after unilateral electrolytic lesion of the locus coeruleus (LC). 2. Lesion of the LC of one side decreased the tonic contraction of the ipsilateral limb extensors, but greatly increased the amplitude of modulation and the response gain of the corresponding triceps brachii to animal tilt; however, no change in the phase angle of the responses was observed. A slight increase in the response gain affected also the contralateral triceps brachii. 3. The postural asymmetry described above was followed from time to time by short-lasting episodes of postural atonia, which affected not only the ipsilateral but also the contralateral limb extensors. These episodes were also associated with a suppression of the EMG responses of the triceps brachii of both sides to sinusoidal stimulation of labyrinth receptors. 4. The episodes of postural atonia which appeared after unilateral lesion of the LC were not associated with rapid eye movements; however, the slow horizontal eye movements, which may occur in normal decerebrate animals, increased in amplitude throughout these episodes. Both the postural atonia as well as the related suppression of the vestibulospinal reflexes, which lasted for 5-10 min, disappeared either spontaneously or following acoustic or somatosensory stimulations. 5. Histological controls indicated that unilateral lesions limited to the caudal part of the LC produced only a permanent decrease in postural activity of the ipsilateral limbs, associated with an increase in gain of the vestibulospinal reflex. However, in order to elicit episodes of bilateral postural atonia associated with the suppression of the vestibulospinal reflexes it was necessary to extend the lesion to more rostral aspects of the LC. 6. Since the effects described above were similar to those elicited in decerebrate cats by local injection of cholinergic agonists into the dorsal part of the pontine reticular formation, we postulated that the postural atonia as well as the related suppression of the vestibulospinal reflexes was due to transient release from LC inhibition of these dorsal pontine reticular structures, which might in turn excite the medullary reticulospinal neurons, thus leading to inhibition of the extensor motoneurons.(ABSTRACT TRUNCATED AT 400 WORDS)     

Central neural stimulation of respiration in unanesthetized decerebrate cats.

A previously reported central neural respiratory control process was restudied in unanesthetized decerebrate cats during spontaneous breathing, and during conditions of constant chemical stimulation where phrenic nerve activity was used to quantitate respiratory output. Respiration was increased by carotid sinus nerve stimulation. The pattern of respiration was examined at the cessation of such stimulation. In spontaneously breathing animals, active hyperventilation (HV) was followed by hyperpnea for up to 30 s and never by apnea. Passive HV was always followed by apnea. In animals with controlled chemical conditions, the transient at the end of stimulation consisted of two components, the first an immediate decrease in respiratory output and the second a slow decrease with a period of over 5 m. It is suggested that a facilitatory feedback process, probably located in the reticular activating system, maintains respiratory output for some time after cessation of a stimulus. This study duplicates the results of previous studies and shows that no area of the brain above the pons is required for the mechanism's operation.     

Muscarinic receptors modulate intracellular Ca2+ concentration in hyaline cells of the chicken basilar papilla

Nonsensory hyaline cells border the sensory epithelium of the auditory end-organ (basilar papilla) in birds and reptiles. Their innervation by cochlear cholinergic efferent fibers and the presence of contractile proteins suggest that hyaline cells may actively regulate basilar membrane mechanics. The cholinergic pharmacology of hyaline cells was studied by measuring the intracellular calcium concentration ([Ca(2+)](i)) of fura-2-loaded cells in the chicken cochlea in vitro. Superfusion of the cholinergic agonist carbachol produced a dose-dependent increase in hyaline cell [Ca(2+)](i) (EC(50)=1.05 micromol l(-1)) and small responses in short hair cells. Calcium increases in hyaline cells were evoked by the muscarinic agonists oxotremorine (10 micromol l(-1)) and muscarine (100 micromol l(-1)) whereas nicotine (100 micromol l(-1), 200 micromol l(-1)) was without effect. Carbachol-evoked responses were blocked by the muscarinic antagonist atropine (>or=10(-13) mol l(-1)) and were unaffected by the nicotinic antagonists d-tubocurare (100 micromol l(-1), 1 mmol l(-1)) and hexamethonium (100 micromol l(-1)). Responses persisted in the absence of extracellular Ca(2+) and were abolished by thapsigargin (1 micromol l(-1)). These results indicate that the cholinergic-stimulated increase in hyaline cell [Ca(2+)](i) is due to a muscarinic-mediated release of Ca(2+) from intracellular stores. This is the first evidence that hyaline cells possess a muscarinic receptor whose activation causes mobilization of intracellular Ca(2+).     

Slow respiratory stimulant effect of hyperoxia in chemodenervated decerebrate cats.

A direct stimulating action of oxygen on the CO2 respiratory control system was determined from steady-state and dynamic observations in unanesthetized decerebrate cats. In peripheral nerve-intact animals, inhalation of oxygen (1 atm) produced a small but significant shift to the left as well as a decrease in slope in the steady-state VT vs. log PACO2 relationship. Carotid sinus neurotomy more than doubled the shift, to the extent that the mean PACO2 apneic point was lowered by 6.5 mmHg. Neither vagotomy nor chronic ablation of the area postrema had any detectable influence on the stimulating effect of oxygen on CO2 responsiveness. The arterial-alveolar PCO2 difference, prior to and following carotid chemo-denervation, remained unchanged or was increased by a negligible amount during oxygen inhalation. The oxygen threshold for respiratory stimulation, obtained isocapnically, occurred between 115 and 200 mmHg; VT then increased exponentially tending to level off as PAO2 approached 1 atm. The dynamic response to sudden presentation of oxygen after carotid chemodenervation consisted of a monotonic rise in VT, starting after 20-30 s with a t 1/2 of about 75 s.     

Muscarinic cholinergic receptors in goldfish retina.

Using ³H-Quinuclinidyl Benzilate (³H-QNB) as a high affinity ligand for quantitative studies of specific binding to muscarinic cholinergic receptors we have demonstrated the presence of such receptors in homogenates of goldfish retina. Only one set of binding sites could be detected with an apparent dissociation constant of 1.9 × 10^?10 M and a density of 53.5 fentomoles per mg of protein. The receptor sites become saturated at a QNB concentration of 1.2 nM. The pharmacological profile of the specific binding is similar to those described for homogenates of beef and chick retina, as well as for rodent brain and smooth muscle.     

Regional intercostal activity during coughing and vomiting in decerebrate cats.

Regional variations in the discharge patterns of the internal and external intercostal muscles of the middle and caudad thorax were studied in decerebrate, spontaneously breathing cats during coughing and vomiting. Coughing, induced by electrical stimulation of the superior laryngeal nerves, consisted of increased and prolonged diaphragmatic activity followed by a burst of abdominal activity. Mid-thoracic external and internal intercostal muscles discharged synchronously with the diaphragm and abdominal muscles, respectively. Caudal external and internal intercostal muscles, however, discharged synchronously with the abdominal muscles. Vomiting, induced by stimulation of the lower thoracic vagi, consisted of a series of synchronous bursts of diaphragmatic and abdominal activity (retching) followed by a prolonged abdominal discharge after the cessation of diaphragmatic activity (expulsion). Caudal external and internal intercostals discharged in phase with diaphragmatic and abdominal activity but both mid-thoracic intercostal muscles discharged out of phase with these muscles. These results indicate major differences in the control and functional roles of intercostal muscles at different thoracic levels during these behaviours.