In awake rats the latency of auditory startle recorded electromyographically in the neck is about 5 ms, suggesting that the primary component of this brainstem reflex is mediated by a neural circuit with only a few synapses. In the present work, neural relays on acoustic head startle circuit are studied in alpha-chloralose-anesthetized rats by means of precise measurements, at putative brainstem relays, of the click-evoked potential latency and of the latency of nuchal EMG startle-like response elicited electrically from each recorded site using the same bipolar electrode. Allowing 0.6 ms for total synaptic transmission time in every relay nuclei, systematic comparisons of the shortest latencies of evoked potentials and shock-elicited startle, as well as estimations of conduction velocities in pathways from cochlea to C1-C5 spinal cord, suggest that one primary acoustic head startle circuit consists of ventral cochlear nucleus (postsynaptic evoked potential: 1.4 ms; startle: 3.6-4.0 ms), ventral nucleus of the lateral lemniscus (evoked potential: 2.3 ms; startle: 2.7-2.8 ms), medial bulbar reticular formation (evoked potential: 3.2-3.6 ms; startle: 2.1 ms), spinal interneuron and motoneuron. The nucleus reticularis pontis caudalis (NRPC) cannot be considered as an head startle relay intercalated between the ventral nucleus of the lateral lemniscus (VNLL) and the medial bulbar reticular formation (MBRF) because mean latencies of field potentials in the pontine RF and the LL nucleus are the same (2.3 ms). Moreover, startle-like responses in neck muscles are elicited through the three brainstem regions with latency differentials which exclude the possibility of a classical synaptic delay either between VNLL (2.8 ms) and NRPC (2.5 ms) or between NRPC and bulbar RF (2.1 ms). Nevertheless, NRPC probably remains a main primary relay on the acoustic startle circuitry; very short latency auditory responses (2.3 ms) are evoked in NRPC by clicks, and low current stimulations of this reticular region produce startle-like activity in neck muscles with a latency of only 2.5 ms. Two other alternative paths consisting of the VCN and NRPC which then would project directly, or through an unknown bulbar site, upon the spinal motor center are hypothetically proposed in conclusion.

Using an electrical stimulation of the reticulospinal tract at the level of the medial longitudinal fasciculus, the effects, and the neurochemical mechanisms of these effects, of a progressive increase in helium-oxygen pressures, up to 50 bar, on the spinal cord excitability in the chronic rat are investigated. In control animals, high pressure exposure over 30 bar was found to increase markedly the electromyogram response evoked in nuchal muscles. This startlelike response was monosynaptically induced by stimulation of the reticulospinal tract. Conversly, no hyperbaric alteration in spinal excitability has been observed in animals pretreated with the classical 5-HT antagonist drug metergoline. These results emphasize the importance of spinal cord as a potential target for mediating hyperbaric effects on sensorimotor behaviors (i.e., motor disturbances of the HPNS). Moreover, our work suggests that serotonin could be implicated in hyperbaric spinal cord hyperexcitability.

In three experiments, startle responses to brief intense tone-bursts (30 msec, 110 dB, 6000 Hz) and single pulse (0.1 msec) stimulation of the cochlear nucleus and the nucleus reticularis pontis caudalis are studied under high pressures of heliox (from 0 bar to 50 bars) in the rat. For each rat (N = 12), mean amplitude and latency changes in startle responses (nuchal electromyography and whole-body accelerometry) are compared at normobaric pressure and during compression, at a speed of 100 bar/H. The results indicate that high pressures decrease (50% of control size) tone evoked startle by acting on the peripheral auditory organ, probably through middle and/or inner ear barotrauma. The large increases in electrically-elicited startle (250% of control size) from the cochlear and reticular nuclei, under hyperbaric conditions, suggest that high pressures affect sensorimotor reactivity by excitatory action on synaptic transmission in the relays of the acoustic startle reflex arc at the lower brainstem and spinal levels. Startle latencies remain unaffected by the heliox high pressures studied here.

Discriminative stimulus control with the tricyclic anti-depressant imipramine was attempted in three groups of rats; two of which were subjected to artificially stressful conditions. Only the unstressed group were shown capable of discriminating between the stimulus properties of intraperitoneal 10 mg/kg imipramine and saline in a two-lever, food-motivated operant task. Discriminative performance with decreasing doses of imipramine was shown to be dose-responsive. The ability to discriminate the interoceptive cue produced by imipramine was observed to transfer to a 10 mg/kg dose of both amitriptyline and desmethylimipramine. The results suggest a common tricyclic anti-depressant cueing property.

Young DA/HAN strain rats were submitted to an equilibrium test consisting in maintaining equilibrium upon a rotorod rotating at 10 or 20 rpm. They were either intact or lesioned, the lesion consisting in destruction of the inferior olivary complex (IOC) by 50–95 mg/kg i.p. administration of 3-acetylpyridine (3-AP) at day 15, followed, 2 to 4 h later, by i.p. injection of niacinamide (300 mg/kg). All the 3-AP-treated animals included in this study were completely lesioned, the extent of the lesion being estimated by both the response of the rats to harmaline and histological controls at the end of the experiments. The IOC lesioned rats were either naive (tested at one given day) or trained every day (10 trials per day); among the latters, some were trained before and after the lesion, the others being trained either before or only after. Control rats were submitted to the same training schedule. Both quantitative (time during which the animals maintained the equilibrium upon the rotating rod) and behavioral data (strategy used by the animals to maintain equilibrium) were obtained. The results demonstrate that, compared to those of control rats, the quantitative and behavioral scores of the IOC lesioned animals were altered. Comparison of naive and trained animals shows that the impairment of the equilibrium behavior is not only due to the ataxia provoked by the IOC lesion but is also due to cognitive deficits. However, prelesion training facilitates the acquisition of a more efficient postlesion equilibrium behavior. From these results, it can be concluded that the olivo-cerebellar pathway is involved in the adaptation of motor behavior to the environmental conditions.

A somesthetic inhibitory projection onto rubrospinal cells in the cat is described. It is suggested that the pathway, which is not dependent upon an intact cerebellum or motor cortex, travels through the dorsal columns of the spinal cord. The second order neurons seem to impinge upon inhibitory interneurons situated within the red nucleus itself. The burst activity in such interneurons might account for the IPSPs seen in rubro-spinal cells.In agreement with the idea that the red nucleus may be part of a feed-back loop through the periphery, the pathway described here could be the link giving suppression of rubral activity during some phases of limb movement.

The effects of harmaline, an indoleamine and a MAOI, were tested on the acoustic stratle pattern. EMG measures of the startle reflex, the pinna reflex as well as the characteristic of the vertex evoked responses to brief intense tone burst (60 msec, 110 dB,8000 Hz) were simultaneously studied in 4 alert guinea-pigs. The basic experimental design was a 4 latin square, with the treatments being given at 2 day intervals. The four harmaline-HCI treatments were isotonic saline, 0.25 5.0 and 10.0 mg/kg. Compared with saline baselines, all the doses resulted, throughout the 60 min session, in overall high significant depressions of the startle reflex, the pinna reflex and the initial wave of the acoustic evoked potential at the vertex. In contrast, harmaline had little or no influence on amplitude and latency of the late wave of the vertex response. The effects of harmaline on the general behavior of the guinea-pig are also reported. These results may support an involvement of serotonergic systems in the modulation of the sensory-motor reactivity at the brainstem level. Nevertheless, the probab;y more complex cortical processes involved in startle responsivity do not appear univocally affected by the indoleamine drugs such as harmaline.

High pressures elicit a high-frequency tremor (8–12 c/sec) in mammals, the mechanisms of which are still unknown. The present study shows that: (1) in spite of many similarities observed between the EMG characteristics of harmaline-induced tremor and pressure-induced tremor, cerebellar lesions which suppress the harmaline-induced tremor, do not modify the characteristics of the pressure-induced tremor; (2) at depth, the caudal part of the spinal cat (section at T9–T10 spinal level) displays irregular spontaneous EMG activities which can be clonic or rhythmic (4–8 c/sec), and a neuromuscular stretch hyperreflexivity. These data suggest that the origin of the pressure-induced tremor is spinal and neuromuscular rather than cerebellar.

We previously reported induction or suppression by juxtafastigial stimulation of the rhythmic complex spike discharge of Purkinje cells in harmaline treated rats. In this paper we show that this modulation of the cerebellar rhythmic activity implies the involvement of inferior olive neurons. These results are discussed in the general framework of the olivo-cerebello-bulbar circuitry. A modulatory control of the inferior olive neuron activity by the raphe system is suggesed to explain part of these results.

In the anaesthetized rat, harmaline induces an olivary activation which results in rhythmic complex-spike (CS) discharges of Purkinje cells (4--8/sec) in the vermian cortex. The temporal organization of the rhythmic CS activity was studied. While some Purkinje cells present long periods of continuous rhythmic activity, the rhythmic CS discharge of other cells is modulated by periodical suppression of activity, with a total cycle length of about 10 sec. This organization can be modified by electrical stimulation of the juxtafastigial region (JF). During periods without spontaneous rhythmical CS firing, single JF shocks produce a late reflex response (200--300 msec) of the Purkinje cells, which appears as a repetitive sequence of CS (up to 30) at the harmaline-like induced frequency. The response obtained is the same whether the electrical stimulus is single or given in succession at regular intervals; however, in order to obtain such an effect, the frequency of the JF stimulation has to be inferior to the rhythmic CS frequency produced by the drug. At a higher stimulation rate (10 c/sec, 3 sec) the JF-induced response of Purkinje cells is abolished and we observe the suppression--4 to 8 sec following stimulation - of any rhythmic CS activity. This experimental modulation of rhythmic activity of the Purkinje cells (inducement or suppression of the CS firing), controlled indirectly by the olivary system, reproduces the spontaneous fluctuations of the thythmicity under harmaline. A neurophysiological model is presented and the functional significance of the results is discussed.

Multinuit activity from the inferior olive was recorded in chronic cats during a learned motor task. The animals were trained to perform a succession of rapid flexion-extension arm movements alternating with two maintained postures. No significant differences were observed in the olivary activity during maintained postures. However an increase of activity occurred before the beginning of the flexion detected on the biceps EMG recordings. The first modifications of olivary activity occurred in synchrony with postural reorganization preceding the flexion. This latter involved primarily the triceps. The increase of activity took place during the execution of movement and ended after the reaching of the target.

Single unit activity of vermian oculomotor cortex (Lobules V, VI, VII) and conjugated horizontal rapid eye movements were recorded in the cat, during wakefulness (W) and paradoxical sleep (PS). Correlation between cerebellar and oculomotor events showed the following findings. During PS the units — mostly Purkinje (P) cells — all increased their rate of discharge (mossy fiber activation for P cells) in coincidence with saccadic movements. Two kinds of movement related cells were observed: (i) Most of the units showed an increase of their discharge rate together with occasional bursts. These events were related to magnitude and rate of the saccades without accurate synchronization. (ii) Some cells showed a burst type activation strictly synchronized with the rapid eye movements of sleep. During W, two thirds of the units changed their pattern of discharge (mossy fiber activation for P cells) with waking ocular activity. Modifications of discharge patterns were very different from cells to cells (activation or suppression, increase or decrease in the rate of discharge). Many cells had an accurately synchronized response with the saccades. Some units had a directional reactivity, others gave a similar response for opposite eye movements. P cells showed an increase of their climbing fiber driven activity during PS with eye movements compared with PS without saccades. During PS and W, complex spikes discharges of P cells evidently showed no accurate relation to saccadic eye movements. Functional significations of the above described events are also discussed.

Summary (1) In order to learn what is the role of climbing fibers (CF) in the cerebellum functions, recordings were obtained from single Purkinje cells (P cells) in free moving cats. The paper reports results of a statistical investigation of P cell responses — complex spikes — to CF activation. Spontaneous discharges of 42 P cells in the vermian lobules V-VI were studied in relation to active wakefulness (AW), quiet wakefulness (QW), slow-wave sleep (SWS) and paradoxical sleep (PS). (2) Morphological observations on P cell discharges and analysis of firing patterns of complex spikes (CS) and simple spikes (SS) have allowed us to characterize the CF activation in the natural conditions. In every behavioral state, the CS occurred at a very slow (around 1/sec) and irregular (0–6/sec) rate. Examples of P cell discharges apparently induced by simultaneous climbing and mossy fiber activations are presented as mixed spikes. (3) Comparison of average frequency of CS during AW and QW did not show any significant result. CS rate decreased moderately during SWS compared to QW, but the slightly lower mean rate in SWS was only due to P cells of the posterior cerebellum. During the PS, the mean rate of CS was at a higher level than those in waking or SWS. The 18 units studied all increased mean firing rate from SWS to PS. During periods of PS with dominant phasic activity the P cells showed the highest mean CS rates. Even in periods of PS with dominant tonic activity the mean CS rate was significantly higher than during SWS, but the fast cells in SWS decreased their firing during tonic periods of PS. Though phasic rate changes in PS occur in association with saccadic eye movements of sleep, the relationship is only a statistical one. (4) In every behavioral state, a striking feature of the CS patterns was irregularity of inter-spike intervals. The variability in CS sequences was evaluated in terms of standard deviation (absolute variability) and coefficient of variation (relative variability). Regardless of behavioral state, the relationship between mean CS intervals and their standard deviations approximated a linear curve. The highest rate during PS could explain the minimal value of the absolute variability during this state of sleep. Values of coefficient of variation were smaller in QW and SWS; the majority of P cells tend to discharge CS more irregularly during PS and AW than during QW and SWS. (5) CS interval histograms were unimodal, with positive skewness and positive kurtosis. In all states, the distributions of intervals were of Pearson's type I. With increased discharge rate, histograms became more asymmetrical and more leptokurtic. The higher CS rate in PS could explain the increasing skewness and kurtosis during this state of sleep. (6) Changes in CF activation rate account for the major variations in CS patterns observed during PS; state for which results are the most probing. Comparisons between characteristics of CS discharges in chronic and in more classical conditions are made. It is concluded that the CF system must represent a primitive input to the cerebellum.

Multiunit activity from the anterior lobe of the cerebellar cortex (pars intermedia) was recorded in chronic cats during a learned motor task. The animals were trained to perform a succession of rapid flexion-extension arm movements alternating with two maintained postures. No significant differences were observed in the corticocerebellar activity (ECeG) during maintained postures. However an increase of activity occurred before the beginning of the flexion detected on the biceps EMG recordings. The first ECeG modifications occurred in synchrony with postural reorganization preceding the flexion. This latter involved primarily the triceps. The increase of activity took place during the execution of movement and ended with the reaching of the target. The results are discussed in relation to the latest hypotheses on cerebellar involvement in motor regulation.