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Visual evoked response (VER) changes during maturation in the Weddell seal.

Visual evoked responses (VER'S) were recorded from the cortex of immature Weddel seals, 3-365 days of age. Results indicated a high degree of maturity at birth evident from the multiphasic array of waveforms and the comparatively short onset latency of the VER. At low intensities, single flashes evoked an immature secondary response. Topographical distribution of VER's were confined largely to the gyrus immediately adjacent to midline, from the posterior aspect near lambda to the vertex. Recordings from CI-744 dosed seals displayed a well-demarcated developmental sequence of VER's, contrary to VER's recorded in flaxedilized seals. Onset latency and waveform configuration changed concomitantly as a function of age. During the postnatal period from birth to weaning, VER changes were related to major behavioral events such as the seal's first encounter with swimming and diving at 2 weeks of age and weaning at 6 weeks of age.

Age Factors↗

Regional properties of dorsal and ventral hippocampus in suppression of intralaminar thalamic unit responses.

In chloralose-anaesthetized, Flaxedil-paralysed cats, the suppression of extra-lemniscal thalamic units by dorsal and ventral hippocampus was investigated. Unitary responses to test somatic stimuli, recorded in centrolateral and neighbouring thalamic nuclei, were interacted with conditioning electric stimulation in different regions around the hippocampal arch, including parahippocampal gyrus (entorhinal and retrosplenial areas). Stimulation of dorsal (dhc) and ventral (VHC) hippocampus suppressed roughly equal proportions of responses. However, within each of DHC and VHC, effectiveness depended on the region stimulated. In DHC, fields CA1 and CA3, subiculum (SUB), and retrosplenial area, but not field CA4 or dentate gyrus, usually suppressed extralemniscal units at currents below 1.0 mA. In VHC, the most effective regions were entorhinal cortex, CA3, and CA4 with dentate gryus (FD), while stimulation of CA1 or subiculum was almost ineffective, at currents below 1.0 mA. In VHC, the regions were ranked for effectiveness: Entorhinal cortex=CA3 is greater than FD is greater than SUB is greater than CA1. No topographic relationship was found between hippocampal region and thalamic loci for unit suppression. Lemniscal-type unit responses in ventrobasal thalamus were unaffected by stimulation of the hippocampus or parahippocampal gryus. Interruption of the fornix-fimbria system prevented suppression elicited from CA1 of DHC, or from CA3 but not FD of VHC. It had no effect on suppression elicited from retrosplenial or entorhinal cortex. Hippocampal regional variation of effectiveness in suppressing extralemniscal pathways may contribute to the differential behavioural involvements reported for different hippocampal structures.

Animals↗

Myotonia and neuromuscular transmission in the mouse.

The role of neuromuscular transmission and acetylcholine receptors in the phenotypic expression of hereditary myotonia was reinvestigated in two mutants of the mouse, ADR (adr/adr) and MTO (adrmto/adrmto). Three neuromuscular blockers, curare, flaxedil, and alpha-bungarotoxin, did not prevent mechanical myotonia of EDL and soleus muscles from the two mutants. Furthermore, electrical myotonia was demonstrated in isolated ADR muscle fibers devoid of nerve endings. We conclude that neither release nor reception of acetylcholine are important for the mechanism of myotonia in mouse mutants. The previously described suppression of myotonic aftercontractions by high concentrations of curare (Muscle & Nerve 1987;10:293-298) could not be reproduced; rather, a prolongation of aftercontractions was found. The other drugs had no significant effect on myotonic aftercontractions. Because neuromuscular transmission is not involved in human myotonias, this result supports the use of myotonic mice as a model, at least for recessive generalized myotonia (Becker).

Animals↗

Postsynaptic potentials in pacemaker cells: a correlation of behavior in command cells of an electric fish.

Intracellular recordings were made from pacemaker-command cells of the electric organ discharge (EOD) of the weakly electric fish Eigenmannia virescens. The fish was immobilized with gallamine triethiodide (Flaxedil) which silenced the EOD. A simulated EOD of this fish (ca. 300 Hz) and a sine wave simulating a neighbor, a few Hz higher (+deltaF) or lower (-deltaF) were introduced into the bath to elicit the "jamming avoidance response" (JAR), monitored through the pacemaker potential. We observed that accompanying the JAR there is a minute hyperpolarizing postsynaptic potential (hpsp) superimposed on the pacemaker potential. A shift in the phase of the hpsp occurs with a change in the sign of deltaF, and therefore of the JAR. Assuming that the behaviorally correlated hpsp is inhibitory, it suggests that mutual inhibition may play a role in regulating the synchronous firing frequency of command neurons, which are electrically coupled with one-another. Scheich and Bullock (1974) proposed a neuronal scheme for the JAR in which they suggest that two systems (P and T) operate together in the nervous system. The T system affects the pacemaker cells at a precise, variable phase of the pacemaker cycle. Although the present results indeed reveal a shift in the hpsp with a change in the sign of deltaF, the actual significance of this shift remains to be evaluated. The unexpected direction of the shift suggests either that the hpsp is excitatory at the phases when it occurs, or that effectiveness of inhibition decreases at later phases in this case instead of increasing as in other cases, or that the hpsp opposes the JAR. The parallel P system is probably more important in explaining the JAR, acting by a DC level control rather than a phase control.

Action Potentials↗

Avian photogenic epilepsy and embryonic brain chimeras: neuronal activity of the adult prosencephalon and mesencephalon.

Photogenic genetic epilepsy was studied in an avian model, using either the Fayoumi epileptic chicken (Fepi) or neural chimeras obtained by replacement of embryonic brain vesicles in normal chickens with those of Fepi embryos. In these two kinds of animals motor seizures accompanied by electroencephalographic (EEG) desynchronization and flattening (DF) were evoked by intermittent light stimulation (ILS). In chimeras with only the prosencephalon grafted, motor seizures were less severe but DF remained. ILS-induced DF persisted under paralysis by gallamine triethiodide (Flaxedil). Extracellular recordings were made in the prosencephalon (wulst) and in the mesencephalon (optic tectum) of paralysed animals. Units recorded in the prosencephalon of Fepi and chimeras showed abnormal interictal bursting activity, distinctly different from the non-epileptic Fayoumi heterozygotes (Fhtz) and normal chickens. The mesencephalic units of Fepi and chimeras having both prosencephalon and mesencephalon grafted showed two types of abnormal activities during ILS-induced DF, which were distinct from the non-epileptic chickens: type I neurons displaying early, high sensitivity to ILS followed by a prolonged suppression of activity; type II neurons displaying an early and prolonged suppression of activity. The results are discussed with respect to the brain structures generating ictal and interictal EEG activities and motor seizures.

Animals↗

Vestibular responses in the rhesus monkey ventroposterior thalamus. II. Vestibulo-proprioceptive convergence at thalamic neurons.

The vestibular thalamic relay in the Rhesus ventrobasal complex, identified in a previous field potential study (part I, Deecke et al., 1974), has now been investigated with neuronal recordings in the thalamus in order to clarify its functional role. In part I, short latency responses (2.5 msec) were found in the corner between VPL, VPM and VPI nuclei, largely including dorsal portions of the VPI nucleus. Field potentials of somewhat longer latency (4-5 msec) were recorded in VPL and in other thalamic nuclei, including the posterior nuclear group. Neuronal responses were recorded in thalamic nuclei of awake flaxedilized Rhesus monkeys. Cells not responding to vestibular stimulation (round window polarisation of either labyrinth) were ignored. The great majority (80%) of those neurons responding to labyrinth polarisation showed convergence with deep somatic (proprioceptive) input from joints and muscles of vertebral column and limbs. 60% of these bimodal neurons responded to movement of cervical joints. Very few vestibularly responsive cells received cutaneous (6.6%), non-optokinetic visual or auditory (2.6% each) input. Proprioceptive fields tended to be large, frequently involving more than one joint, and could be even bilateral. For a few cells the pattern of vestibulo-proprioceptive convergence could be fitted to a coordinated body position that might occur during normal locomotion. 78% of the cells responded to polarisation of both labyrinths, indicating strong bilateral projection.

Animals↗

Stimulus dependent colour specificity of monkey lateral geniculate neurones.

From six flaxedilized rhesus monkeys neuronal activity of 75 cells in the dorsal, and 45 cells in the ventral layers of the lateral geniculate body was recorded. Responses to large fields switched on and off, to moving slits, and to moving spots were obtained for several wavelengths. In the dorsal layers, colour selectivity was strong for large field stimuli but weak for moving spots. Residual colour selectivity for spots was more evident for smaller eccentricities. In comparison, ventral layer cells were less colour selective for all stimuli used. Large field responses were weak, they often consisted of a sequence of excitation and inhibition. The subdivision of the dorsal cells into different colour opponency types based on large field responses is compared to the subdivision based on centre and surround functions. Results are compared to colour responses in retina and visual cortex, and the tonic and phasic cell type subdivision is discussed.

Action Potentials↗

Harmaline-induced tremor. I. Regional metabolic activity as revealed by [14C]2-deoxyglucose in cat.

Changes of local cerebral glucose consumption under the effect of tremogenic doses of harmaline were studied. To find the brain structures activated by the drug, the autoradiographic method using [14C]2-deoxyglucose was applied to young cats. After administration of harmaline, the animals were paralized with flaxedil. Results were compared to a group of control animals not injected with the drug, but submitted to the same experimental protocol. Increases of neuronal activity were observed in several structures. A) Among the relays of the olivo-cerebello-fastigio (and vestibulo)-reticulo-spinal circuit that had been claimed to fire at the frequency of the tremor, labeling was found in: 1. selected portions of the inferior olive including the medial accessory olive and the caudolateral part of the dorsal accessory olive; 2. the molecular layers of the cerebellar cortex including vermian and paravermian zones. Labeling of the olivo-cerbellar system was therefore larger than the compartment controlling the fastigial nucleus and extended to that controlling the interpositus nucleus. B) Other structures not under the direct control of the olivo-cerebellar system displayed increased radioactivity under harmaline: lateral reticular nucleus, nucleus reticularis tegmenti pontis, red nucleus and basal ganglia. Part of the nucleus ambiguus, intensely labeled in the control animals, showed decreased radioactivity under harmaline. The experiments were repeated with the same protocol in another group of animals with unilateral sections of the inferior cerebellar peduncle in order to distinguish between a direct pharmacological influence and a nervous one. Marking of the basal ganglia was not affected by pedunculotomy, suggesting a direct "pharmacological" action of the drug in this cases. On the other hand, marking of the other labeled structures was asymmetric or suppressed by pedunculotomy, and therefore could result from a "nervous" effect secondary to activation of the inferior olive.

Alkaloids↗

Control of locomotion in marine mollusc Clione limacina. X. Effects of acetylcholine antagonists.

The swimming central pattern generator (CPG) of the pteropod mollusc Clione limacina is located in the pedal ganglia. It consists of three groups of interneurons (7, 8, and 12) which generate the rhythmical activity and determine the temporal pattern of the motor output, that is, phasic relations between different groups of motor neurons supplying dorsal (group 1 and 3 motor neurons) and ventral (group 2 and 4 motor neurons) muscles of the wings. In this work peripheral and central effects of acetylcholine (ACh) antagonists on the swimming control in C. limacina has been studied. The ACh antagonist atropine blocked transmission from the wing nerves to wing muscles, while gallamine triethiodide (Flaxedil), d-tubocurarine, and alpha-bungarotoxin did not affect the neuromuscular transmission. In the pedal ganglia, the ACh antagonists atropine and gallamine triethiodide blocked inhibitory postsynaptic potentials (IPSPs) produced by group 8 interneurons onto group 7 interneurons and motor neurons of groups 1 and 3. d-Tubocurarine and alpha-bungarotoxin did not affect IPSPs produced by group 8 interneurons. Although atropine and gallamine triethiodide blocked IPSPs produced by group 8 interneurons in antagonistic neurons, these drugs did not influence excitatory postsynaptic potentials (EPSPs) produced by group 8 interneurons onto group 12 interneurons. The main pattern of the swimming rhythm with an alternation of two phases of the swimming cycle persisted after elimination of inhibitory connections from group 8 interneurons to antagonistic neurons by the ACh antagonists. This suggests that there are redundant mechanisms in the system controlling C. limacina's swimming. This redundancy ensures reliable operation of the system and contributes to its flexibility.

Acetylcholine↗

Characteristics of habituation in visceral systems.

The conditions of development of habituation were studied in cats anesthetized with a mixture of chloralose and pentobarbital, and immobilized with flaxedil, by recording evoked potentials (EP) in the cerebral cortex. Cessation of stimulation was shown to lead to spontaneous recovery of EP, and the rate of its development depended on the number of stimuli applied in the habituation test. The use of repeated tests with constant intervals between them led to incomplete recovery of the amplitude of EP and to the more rapid development of habituation in subsequent tests (the habituation potentiation effect). During the development of habituation an extrastimulus restored the amplitude of EP (dehabituation). Repeated use of the extrastimulus reduced the effectiveness of its action (habituation of dehabituation). The results obtained corresponded to the features of habituation in other sensory systems.

Animals↗

Compensatory plasticity of the brain under conditions of its injury.

The possibility of the utilization of the galvanic skin response (GSR) as a test for the analysis of compensatory processes under the conditions of natural compensation and with the use of functional biofeedback was studied in experiments on cats anesthetized with chloralose and immobilized with flaxedil, as well as in clinical conditions in healthy children and children suffering from childhood cerebral palsy (CCP). It was demonstrated in this study that the habituation of the GSR is disturbed in the case of unilateral brain trauma. These differences level out a year after the brain trauma. When functional biofeedback is used to accelerate habituation processes of a compensatory character, the GSR of the right and left sides of the body equalize and approximate that observed in healthy children. This study is yet another confirmation of the advantage of functional biofeedback as compared with traditional treatment methods. The data obtained also make it possible to believe that the habituation of the GSR may be useful not only for the analysis of the depth and level of the injury of nerve tissue, but for the objective assessment of compensatory restorative processes as well.

Adolescent↗

Effects of microinjection of L-glutamate into locus coeruleus complex area on respiration.

The experiments were performed on 55 rabbits vagotomied, anesthetized with urethane and immobilized with flaxedil. Injection of L-glutamate (L-glu) into the locus coeruleus complex (Lc-Sc) area led to a marked increase in respiratory frequency (RF) and phrenic nerve discharge rate (phr.d) (16 +/- 3.5% and 6.5 +/- 2.5%; P < 0.01 and P < 0.05, respectively), a decrease in inspiratory and expiratory duration, and no obvious change in blood pressure (Bp) was observed. While prazosin (0.5 micrograms/microliters), yohimbin (4 micrograms/microliters) and propranolol (2 micrograms/microliters) were preinjected into the nuclei tractus solitraii (NTS) respectively, the above-mentioned effects of L-glu on respiration was blocked. These results indicate that the excitation of neurons in the Lc-Sc can induce an increase in RF and phr. d and the excitative effect of L-glu on RF was mediated by alpha 1, alpha 2 and beta-receptors in the NTS, while the effect on phr.d was mediated differently.

Animals↗

A comparative study of hearing ability in fishes: the auditory brainstem response approach.

Auditory brainstem response (ABR) techniques, an electrophysiological far-field recording method widely used in clinical evaluation of human hearing, were adapted for fishes to overcome the major limitations of traditional behavioral and electrophysiological methods (e.g., invasive surgery, lengthy training of fishes, etc.) used for fish hearing research. Responses to clicks and tone bursts of different frequencies and amplitudes were recorded with cutaneous electrodes. To evaluate the effectiveness of this method, the auditory sensitivity of a hearing specialist (goldfish, Carassius auratus) and a hearing generalist (oscar, Astronotus ocellatus) was investigated and compared to audiograms obtained through psychophysical methods. The ABRs could be obtained between 100 Hz and 2000 Hz (oscar), and up to 5000 Hz (goldfish). The ABR audiograms are similar to those obtained by behavioral methods in both species. The ABR audiogram of curarized (i.e., Flaxedil-treated) goldfish did not differ significantly from two previously published behavioral curves but was lower than that obtained from uncurarized fish. In the oscar, ABR audiometry resulted in lower thresholds and a larger bandwidth than observed in behavioral tests. Comparison between methods revealed the advantages of this technique: rapid evaluation of hearing in untrained fishes, and no limitations on repeated testing of animals.

Acoustic Stimulation↗

Stimulation of protein methylase II from Torpedo marmorata by cholinergic effectors.

The enzymatic transfer of methyl groups mediated by protein methylase II onto proteins of the electroplaque tissue of Torpedo marmorata is described. The protein methylase II resides to the extent of 80% in the cytosol and 20% in the acetylcholine receptor-rich membrane. The kinetics of the methyl-group transfer are characteristically different in the cytosol and membrane fractions. The reaction is inhibited by phosphate with IC50 = 450 microM. The cholinergic effectors carbamoylcholine, flaxedil and alpha-bungarotoxin applied to the outside of the acetylcholine receptor-rich membrane vesicles stimulated the protein methylase II which is exclusively located inside the vesicles. The stimulation is biphasic and transient, yielding an increased initial velocity and a peak of activity at 2 min after the addition of the effector. The stimulation by carbamoylcholine is qualitatively similar to that elicited by the antagonist. In addition, the protein methylase II is stimulated transiently by phospholipase A2 with a time-course clearly different from that of the cholinergic effectors. We conclude that the conformational change in the receptor-protein elicited by cholinergic effectors is efficiently transduced to the cytoplasmic methylation sites.

Animals↗

Catecholamines released from cerebral cortex in the cat; decrease during sensory stimulation.

In an attempt to determine the functional role of catecholamine (CA) nerve terminals in cerebral cortex the release of endogenous norepinephrine (NE) and dopamine (DA) into superfusates from visual and somatosensory cortex of the cat have been measured by a sensitive radiometric enzymatic assay based on the methylation of CA by catechol-O-methyltransferase (COMT) in the presence of a [3H]-methyl donor and followed by resolution of 3H derivatives through a series of organic extractions. In the flaxedilized animal maintained under local anaesthesia with artificial respiration the concentration of CA measured in 30-min superfusates was fairly constant in a given experiment under basal conditions without sensory stimulation, but varied widely from one experiment to another. Variations in NE were often independent of those for DA. For visual cortex the average basal release of NE in experiments was 20.09 +/- 3.64 pg/min/sq.cm while the average for DA was 34.01 +/- 7.62 pg/min/sq.cm. In all experiments intermittent visual stimulation (15/sec) produced a significant reduction in release rate averaging about 42% for NE and 64% for DA in visual cortex. The reduction was relatively non-specific since visual or somatic sensory stimulation produced a decrease in release from both visual and somatic sensory cortical areas. Since it has been shown that there is a relatively non-specific increase in acetylcholine (ACh) release from sensory cortex during stimulation, it is proposed that ACh may regulate CA release at presynaptic CA terminals in the cortex as it does in the periphery. A marked increase in CA release observed on perfusing with nicotine or atropine is consistent with this hypothesis.

Acetylcholine↗

Messages conveyed by spinocerebellar pathways during scratching in the cat. I. Activity of neurons of the lateral reticular nucleus.

(1) Signals transmitted to the cerebellum by the spino-reticulocerebellar pathway (SRCP) during scratching were studied. For this purpose, the activity of neurons of the lateral reticular nucleus (LRN), which are the last-order neurons of the SRCP, was recorded during scratching in thalamic cats. Scratching was evoked by stimulation of the pinna. LRN neurons were identified antidromically by stimulation of the hindlimb area in the cerebellar anterior lobe. In most experiments, animals were immobilized with Flaxedil, and stimulation of the pinna resulted in fictitious scratching, i.e., in periodical reciprocal activity of flexor and extensor motoneurons typical of actual scratching. (2) During both actual and fictitious scratching, the discharge frequency of LRN neurons was rhythmically modulated in relation with the scratch cycle. Most LRN neurons fired in short high-frequency bursts of spikes which coincided (completely or partly) with the extensor phase of the cycle. In this respect the SRCP differs from the ventral spinocerebellar tract (VSCT) which is maximally active in the flexor phase of the cycle. (3) The firing pattern of LRN neurons during fictitious scratching was similar to that during actual scratching. Therefore, the rhythmical burst firing of LRN neurons is determined mainly by the central mechanisms and not by the rhythmical sensory input. (4) Rhythmical modulation of LRN neurons disappeared after transection of the ipsilateral lateral funiculus of the spinal cord in which spinoreticular fibers are located. On the other hand, considerable reduction of rhythmical activity in descending brainstem-spinal pathways after contralateral hemisection of the spinal cord did not affect the discharge pattern of LRN neurons. These two facts indicate that the SRCP conveys mainly messages about activity of the central spinal mechanisms, and that influences of supraspinal motor centers.on LRN neurons and on spinoreticular neurons are of minor importance. (5) Axonal terminations of LRN neurons are distributed rather evenly over the hindlimb area in the anterior lobe of the cerebellum. Therefore, messages about the events, which happen within the spinal cord in the vicinity of the extensor phase of the cycle, arrive at every point of the hindlimb area.

Animals↗

Activity of Ia inhibitory interneurons during fictitious scratch reflex in the cat.

(1) The fictitious scratch reflex was observed in decerebrate cats immobilized with Flaxedil. The activity of interneurons in the inhibitory pathways from Ia afferents to motoneurons of antagonistic muscles was recorded during scratching. The selected interneurons were supplied by Ia afferents from m. vastus, posterior biceps-semitendinosus and sartorius. (2) Almost all recorded interneurons showed periodic modulation of activity. Their maximal activity in the scratch cycle usually coincided with the maximal activity of motoneurons of those muscles from which the interneurons receive Ia afferents. Excitation of Ia afferents by passive stretch of the muscle or by electrical stimulation of the muscle nerve resulted in the increase of the interneuron activity, without changing its timing in the scratch cycle.

Afferent Pathways↗

Activity of neurons of cerebellar nuclei during fictitious scratch reflex in cat. I. Fastigial nucleus.

The activity of neurons located in the rostral part of the fastigial nucleus was recorded during the fictitious scratch reflex in thalamic cats immobilized with Flaxedil. The activity of most of the neurons was rhythmically modulated in relation to the scratch cycle: they generated bursts of impulses separated by periods of silence or, in a few cases, by periods of reduced activity. The discharge pattern of neurons was usually the same during both ipsilateral and contralateral scratch reflex: in both cases their maximum activity could be observed in the extensor phase of the scratch cycle. Rhythmical modulation of fastigial neurons is determined by signals coming from the central spinal mechanism, generating rhythmical oscillations, via the ventral spinocerebellar tract (VSCT) and the spinoreticulo-cerebellar pathway (SRCP). Results of separate transections of these pathways suggest that the SRCP determines the periodical excitationm of fastigial neurons and the VSCT their periodical inhibition.

Afferent Pathways↗