G. Stampacchia

Responses of locus coeruleus and subcoeruleus neurons to sinusoidal stimulation of labyrinth receptors

In precollicular decerebrate cats the electrical activity of 141 individual neurons located in the locus coeruleus-complex, i.e. in the dorsal (n = 41) and ventral parts (n = 67) as well as in the locus subcoeruleus (n = 33), was recorded during sinusoidal tilt about the longitudinal axis of the whole animal, leading to stimulation of labyrinth receptors. Some of these neurons showed physiological characteristics attributed to the norepinephrine-containing locus coeruleus neurons, namely, (i) a slow and regular resting discharge, and (ii) a typical biphasic response to fore- and hindpaw compression consisting of short impulse bursts followed by a silent period, which has been attributed to recurrent and/or lateral inhibition of the norepinephrine-containing neurons. Furthermore, 16 out of the 141 neurons were activated antidromically by stimulation of the spinal cord at T12 and L1, thus being considered coeruleospinal or subcoeruleospinal neurons. A large number of tested neurons (80 out of 141, i.e. 56.7%) responded to animal rotation at the standard frequency of 0.15 Hz and at the peak amplitude of 10 degrees. However, the proportion of responsive neurons was higher in the locus subcoeruleus (72.7%) and the dorsal locus coeruleus (61.0%) than in the ventral locus coeruleus (46.3%). A periodic modulation of firing rate of the units was observed during the sinusoidal stimulus. In particular, 45 out of the 80 units (i.e. 56.2%) were excited during side-up and depressed during side-down tilt (beta-responses), whereas 20 of 80 units (i.e. 25.0%) showed the opposite behavior (alpha-responses). In both instances, the response peak occurred with an average phase lead of about + 18 degrees, with respect to the extreme side-up or side-down position of the animal; however, the response gain (imp./s per deg) was, on average, more than two-fold higher in the former than in the latter group. The remaining 15 units (i.e. 18.7%) showed a prominent phase shift of this response peak with respect to animal position. Similar results were obtained from the subpopulation of locus coeruleus-complex neurons which fired at a low rate (less than 5.0 imp./s), as well as for the antidromically identified coeruleospinal neurons. The response gain of locus coeruleus-complex neurons, including the coeruleospinal neurons, did not change when the peak amplitude of tilt was increased from 5 degrees to 20 degrees at the fixed frequency of 0.15 Hz. This indicates that the system was relatively linear with respect to the amplitude of displacement.(ABSTRACT TRUNCATED AT 400 WORDS)

Effects of stimulation of vestibular and neck receptors on Deiters neurons projecting to the lumbosacral cord

Abstract1. The activity of lateral vestibular nucleus (LVN) neurons, antidromically identified by stimulation of the spinal cord at T12 and L1, thus projecting to the lumbosacral segments of the spinal cord (lVS neurons), was recorded in precollicular decerebrate cats during rotation about the longitudinal axis either of the whole animal (labyrinth input) or of the body only while the head was kept stationary (neck input). 2. Among the lVS neurons tested for vestibular stimulation, 76 of 129 units (i.e. 58.9%) responded to roll tilt of the animal at the standard parameters of 0.026 Hz, ±10°. The gain and the sensitivity of the first harmonic responses corresponded on the average to 0.47±0.44, SD, impulses·s−1·deg−1 and 3.24±3.15, SD, %/deg, respectively. As to the response patterns, 51 of 76 units (i.e. 67.1%) were excited during side-down and depressed during side-up tilt, whereas 15 (i.e. 19.7%) showed the opposite behavior. In both instances the peak of the responses occurred with an average phase lead of about +21.0±27.2., SD, deg with respect to the extreme side-down or side-up position of the animal. Moreover, the former group of units showed almost a twofold larger gain with respect to the latter group (t-test,p<0.05). 3. Among the lVS neurons tested for neck stimulation, 75 of 109 units (68.8%) responded to neck rotation at the standard parameters. The gain and the sensitivity of the first harmonic responses corresponded on the average to 0.49±0.40, SD, impulses·s−1·deg−1 and 3.30±3.42, SD, %/deg, respectively, thus being similar to the values obtained for the labyrinth responses. However, 59 of 75 units (i.e. 78.6%) were excited during side-up neck rotation and depressed during side-down neck rotation, while 8 of 75 units (i.e. 10.7%) showed the opposite pattern. In both instances the peak of the responses occurred with an average phase lead of +52.0±18.3, SD, deg for the extreme side-up or side-down neck displacements. Further, the former group of units showed a larger gain than the latter group. 4. Histological controls indicated that 102 of 129 (i.e. 79.0%) lVS neurons tested for labyrinth stimulation and 86 of 109 (i.e. 78.9%) lVS neurons tested for neck stimulation were located in the dorsocaudal part of LVN, the remaining lVS neurons being located in the rostroventral part of LVN. 5. The observation that the predominant response pattern of the lVS neurons to roll tilt was just opposite to that of lVS neurons to neck rotation indicates that the motoneurons innervating ipsilateral hindlimb extensors were excited by an increased discharge of vestibulospinal neurons during side-down tilt but they were disfacilitated by the reduced discharge of vestibulospinal neurons during side-down neck rotation; the opposite would occur during side-up animal tilt or neck rotation. These findings were compared with those of previously recorded LVN neurons, whose descending axons were not identified as projecting to upper or lower segments of the spinal cord. It was then possible to evaluate the role that the LVN exerts not only in the control of the limb but also of the neck extensor musculature.

Responses of medullary reticulospinal neurons to sinusoidal rotation of neck in the decerebrate cat

The electrical activity of 132 neurons located in the inhibitory area of the medullary reticular formation, namely, in the medial aspects of the nucleus reticularis gigantocellularis, magnocellularis and ventralis has been recorded in precollicular decerebrate cats during sinusoidal displacement of the neck. This was achieved by rotation of the body about the longitudinal axis of the animal, while maintaining the head stationary. In particular, 85 neurons were activated antidromically by stimulation of the spinal cord at T12 and L1, the remaining 47 units were not activated antidromically. Among these reticular neurons tested, 66 out of 85 (i.e. 77.6%) of the neurons that were, and 31 out of 47 (i.e. 66.0%) of the neurons that were not antidromically activated responded to slow neck rotation at the frequency of 0.026 Hz and at the peak amplitude of displacement of 10 degrees. The units influenced by neck rotation showed a periodic modulation of the firing rate in response to sinusoidal stimulation of neck receptors. In particular, 70 of 97 units (i.e. 72.2%) were excited during side-down neck rotation and depressed during side-up rotation, while 19 of 97 units (i.e. 19.6%) showed the opposite pattern. In both instances, the peak of the responses occurred with an average phase lead of +41 degrees for the extreme side-up or side-down neck displacement. The remaining 8 units (i.e. 8.2%) showed a prominent phase shift of the peak of their response relative to neck position. The proportion of units excited during side-down neck rotation were almost equally distributed throughout the whole rostro-caudal extent of the reticular structures explored. Responses to neck rotation were detectable at 0.25 degrees of peak displacement. The gain (imp./s/deg.) and the sensitivity (%/deg., i.e. percentage change of the mean firing rate per degree of displacement) in responses of reticulospinal neurons decreased by increasing the peak amplitude of neck rotation from 1 to 10 degrees at a frequency of 0.026 Hz. Therefore, the system did not behave linearly with respect to amplitude of stimulation. By increasing the frequency of stimulation from 0.008 to 0.32 Hz at the fixed amplitude of 10 degrees, the gain, sensitivity and phase lead of responses increased for frequencies of neck rotation above 0.051 Hz. Reticulospinal neurons may thus monitor changes in neck position as well as in velocity of neck rotation. Responses of reticulospinal neurons to neck rotation are discussed in relation to the responses to the same stimulus recently described of vestibulospinal neurons originating from the lateral vestibular nucleus.(ABSTRACT TRUNCATED AT 400 WORDS)

Responses of locus coeruleus and subcoeruleus neurons to sinusoidal neck rotation in decerebrate cat

The electrical activity of 99 neurons located in the locus coeruleus-complex, namely in the dorsal (n = 26) and the ventral part of the locus coeruleus (n = 46) as well as the locus subcoeruleus (n = 27), has been recorded in precollicular decerebrate cats during sinusoidal displacement of the neck. This was achieved by rotation of the body about the longitudinal axis of the animal, while maintaining the head stationary. A proportion of these neurons showed some of the main physiological characteristics attributed to the noradrenergic locus coeruleus neurons, i.e. (i) a slow and regular resting discharge, and (ii) a typical biphasic response to fore and hindpaw compression consisting of short bursts of impulses followed by a period of quiescence, due at least in part to recurrent or lateral inhibition of the corresponding neurons. Moreover, 14 out of the 99 neurons were activated antidromically by stimulation of the spinal cord at T12 and L1, thus being considered as coeruleo- or subcoeruleospinal neurons. Among these locus coeruleus-complex neurons tested, 73 out of 99 (i.e. 73.7%) responded to neck rotation at the standard frequency of 0.15 Hz and at the peak amplitude of displacement of 10 degrees. In particular 40 of 73 units (i.e. 54.8%) were excited during side-down neck rotation and depressed during side-up rotation, while 18 of 73 units (i.e. 24.7%) showed the opposite pattern. In both instances the peak of the responses occurred with an average phase lead of +34.2 degrees for the extreme side-down or side-up neck displacement; however, the response gain (impulses/s per deg) was on the average more than two-fold higher in the former than in the latter group of units. The remaining 15 units (i.e. 20.5%) showed phase angle values which were intermediate between those of the two main populations. As to the coeruleo or subcoeruleospinal neurons, 11 of 14 units (78.6%) responded to the neck input, the majority (nine of 11 units, i.e. 81.8%) being excited during side-down neck rotation. Within the explored region, the proportion of responsive units was higher in the locus subcoeruleus (85.2%) than in the locus coeruleus, both dorsal and ventral (69.4%). Moreover, units located in the former structure showed on the average a response gain higher than that found in the latter structures. Similar results were also obtained from the population of locus subcoeruleus-complex neurons which fired at a low rate (less than or equal to 5.0 impulses/s).(ABSTRACT TRUNCATED AT 400 WORDS)

Convergence and interaction of neck and macular vestibular inputs on locus coeruleus and subcoeruleus neurons.

Extracellular recordings were obtained in precollicular decerebrate cats from 90 neurons located in the noradrenergic area of the dorsal pontine tegmentum, namely in the dorsal (LCd,n=24) and the ventral part (LCα,n=40) of the locus coeruleus (LC) as well as in the locus subcoeruleus (SC,n=26). Among these units of the LC complex, 13 were coerulospinal (CS) neurons antidromically identified following stimulation of the spinal cord at T12-L1. Some of these neurons showed the main physiological characteristics of the norepinephrine (NE)-containing LC neurons, i.e., a slow and regular resting discharge and a typical biphasic response to fore- and hindpaw compression consisting of a short burst of excitation followed by a period of quiescence, due, in part at least, to recurrent and/or lateral inhibition. Unit firing rate was analyzed under separate stimulation of macular vestibular, neck, or combined receptors by using sinusoidal rotation about the longitudinal axis at 0.15 Hz, ±10° peak amplitude.Among the 90 LC-complex neurons, 60 (66.7%) responded with a periodic modulation of their firing rate to roll tilt of the animal and 67 (74.4%) responded to neck rotation. Convergence of macular and neck inputs was found in 52/90 (57.8%) LC-complex neurons; in these units, the gain and the sensitivity of the first harmonic of the response corresponded on the average to 0.34±0.45, SD, impulsed·s−1·deg−1 and 3.55±2.82, SD, %/deg for the neck responses and to 0.23±0.29, SD, impulses·s−1·deg−1 and 3.13±3.04, SD, %/deg for the macular responses. In addition to these convergent units, 8/90 (8.9%) and 15/90 (16.7%) LC-complex units responded to selective stimulation either of macular or of neck receptors only. These units displayed a significantly lower response gain and sensitivity to animal tilt and neck rotation with respect to those obtained from convergent units. Most of the convergent LC-complex units were maximally excited by the direction of stimulus orientation, the first harmonic of responses showing an average phase lead of about +31.0° with respect to neck position and +17.6° with respect to animal position. Two populations of convergent neurons were observed. The first group of units (43/52, i.e., 82.7%) showed reciprocal (“out of phase” responses to the two inputs; moreover, most of these units were excited during side-down neck rotation, but inhibited during side-down animal tilt. The second group of units (9/52, i.e., 17.3%) showed parallel (“in phase” responses to the two inputs and they were excited by side-down or side-up neck rotation and animal tilt. The response characteristics of LC-complex neurons to combined neck and macular inputs, elicited during head rotation, corresponded to those predicted by a vectorial summation of the individual neck and macular responses. In particular, “out of phase” units displayed small amplitudes and large phase shifts of their responses with respect to those obtained during individual neck or macular stimulation. In contrast, “in phase” units displayed large responses during head rotation. Some nonlinearities of the responses to combined stimulation of neck and macular receptors, however, were observed. The possibility that the CS neurons contributed, with the vestibulospinal (VS) neurons, to the postural adjustments of the limb musculature during labyrinth and neck reflexes was discussed.

Noradrenergic and cholinergic mechanisms responsible for the gain regulation of vestibulospinal reflexes.

Experiments performed in precollicular decerebrate cats have shown that dorsal pontine structures, including the LC and the related dorsal pRF, play an important role not only in the control of posture but also in the gain regulation of the VS reflexes. The LC neurons, which are not only noradrenergic but also NE-sensitive due to the existence of self-inhibitory synapses acting on a2-adrenoceptors, send inhibitory afferents to the dorsal pRF; on the other hand, these pontine reticular neurons, which are presumably cholinergic as well as cholinoceptive due to the existence of self-excitatory synapses, project excitatory afferents to the medullary inhibitory RS system. The increased discharge of these pontine reticular neurons and the related inhibitory RS neurons following local injection of cholinergic agonists into the dorsal pRF decreased the postural tonus in the ipsilateral limbs but greatly enhanced the amplitude of the EMG modulation and thus the response gain of ipsilateral limb extensors to labyrinth stimulation. This finding did not depend on the decreased postural activity, since it was still observed when the EMG activity was reflexly maintained by an increased static stretch of the muscle. Similar results were also obtained when the discharge of the pontine reticular neurons and the related inhibitory RS neurons was raised after local injection of an a2-adrenergic agonist into the LC, leading to functional inactivation of the noradrenergic LC neurons. On the other hand, an increased postural activity in the ipsilateral limbs as well as a reduced gain of the corresponding VS reflexes were obtained when the discharge of the pontine reticular neurons and the related inhibitory RS neurons was reduced, as shown after local injection of cholinergic agonists into the LC leading to activation of the noradrenergic neurons. There was also evidence that cholinergic excitatory afferents to the LC originated from the ipsilateral dorsal pRF. The effects described above were dose-dependent as well as site-specific, as shown by histological controls. In conclusion, the pontine structures described above operate as a variable-gain regulator acting at the motoneuronal level during the VS reflexes. Since the same structures are also responsible for the spontaneous fluctuations in posture related to the sleep waking cycle, they may well intervene as a control system in order to adapt to the animal state the response gain of limb extensors following labyrinth stimulation.

LABYRINTHINE INFLUENCES ON LOCUS COERULEUS NEURONS

The locus coeruleus (LC) complex, located in the dorsolateral pontine tegmentum, is composed principally of noradrenergic neurons, which project to broad regions of the CNS, including the spinal cord. Experiments were performed in precollicular decerebrate cats to ascertain whether units histologically identified within the LC complex, and having the physiological characteristics of noradrenergic neurons, would respond to sinusoidal stimulation of labyrinth receptors. Among 141 LC complex neurons, 16 of which could be activated antidromically by stimulation of the spinal cord at T12-L1, 80 (i.e. 56.7%) responded to roll tilt of the animal at 0.15 Hz, +/- 10 degrees. The responses were particularly related to the extreme animal displacements, thus being attributed to stimulation of macular utricular receptors. The proportion of responsive units, and also the average gain of the responses, were higher in the LCd and the subcoerular (subLC) area than in the LCa. Moreover in the same structures the majority of units showed a beta-pattern of response (excitation during side-up tilt), which contrasted with the predominant alpha-pattern (excitation during side-down tilt) displayed by the previously recorded vestibulospinal neurons projecting to the same segments of the spinal cord. The role that the noradrenergic coeruleospinal neurons exert in the dynamic control of posture during the vestibulospinal reflexes is discussed.

Cholinergic brainstem sites for gain control of vestibulospinal reflexes in cats

Decerebrate cats were injected with carbachol into the locus coeruleus (LC) or with carbachol or bethanechol into the dorsal pontine reticular formation (pRF) of one side; recordings were made of the tonic contraction of forelimb extensor muscles of both sides and of their responses to sinusoidal roll tilt of the animal. Both drugs had similar effects when injected into the pRF: a decrease in the tonic contraction of limb extensors and a greatly enhanced amplitude and gain with slightly decreased phase lead in the responses to animal tilt of the forelimb extensor, triceps brachii, ipsilateral to the side of injection. Injected into the LC, carbachol produced a response opposite to the above: it increased the tonic contraction of limb extensors ipsilateral to the side of injection, but decreased the amplitude and gain of the EMG responses of limb extensor muscles to labyrinth stimulation induced by sinusoidal tilt. These findings did not depend on changes in posture since they were still observed when postural EMG activity was maintained constant by appropriate changes in static stretch of the muscle. Moreover, the magnitude of the effects increased in a dose-dependent manner. Results suggest that cholinergic activation of dorsal pRF neurons through muscarinic receptors increases the background discharge of medullary inhibitory reticulospinal (RS) system neurons, thus increasing their modulatory influence. Further, it is postulated that cholinergic activation of LC neurons would cause them to inhibit this tonic facilitatory drive by the pRF. Common to both sites of carbachol injection is the increase in phase lag of the EMG response of limb extensors to animal tilt.(ABSTRACT TRUNCATED AT 250 WORDS)