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Dynamic modulation of mossy fiber system throughput by inferior olive synchrony: a multielectrode study of cerebellar cortex activated by motor cortex.

We investigated the effects of climbing fiber synchrony on the temporal dynamics of mossy fiber system throughput in populations of cerebellar Purkinje cells (PCs). A multielectrode technique was used in ketamine-anesthetized rats that allowed both complex and simple spikes (CSs and SSs) to be recorded from multiple PCs simultaneously in lobule crus IIa. Stimulation of the tongue area of the primary motor cortex (TM1) was used to evoke cerebro-cerebellar interaction. At the single PC level, robust short-term interactions of CSs and SSs were observed after TM1 stimulation that typically consisted of an immediate depression and subsequent enhancement of SS firing after the occurrence of a CS. Such modulations of SS rate in a given PC were as robustly correlated to the CSs of simultaneously recorded PCs as they were to the CS on its own membrane-and did not require a CS on its own membrane-indicating a network basis for the interaction. Analyses of simultaneously recorded PCs using the normalized joint perievent time histogram demonstrated that CS and SS firing were dynamically correlated after TM1 stimulation in a manner that indicated strong control of mossy fiber system throughput by CS synchrony. For < or =300 ms after TM1 stimulation, most PCs showed episodic modulations in SS rate that appeared to be entrained by the population rhythm of climbing fiber synchrony. SS rhythmicity also was modulated dynamically by CSs, such that it was depressed by CSs and facilitated by their absence. Like the modulations in SS rate, a given PC's modulation in SS rhythmicity did not require it to fire a CS but was, on those instances, equally correlated to the synchronous CSs of other PCs. The data indicate that the climbing fiber system controls the temporal dynamics of SS firing in populations of PCs by using synchrony to engage intracerebellar circuitry and modulate mossy fiber system throughput.

Action Potentials↗

Evolutionary patterns of cranial nerve efferent nuclei in vertebrates.

All vertebrates have a similar series of rhombomeric hindbrain segments within which cranial nerve efferent nuclei are distributed in a similar rostrocaudal sequence. The registration between these two morphological patterns is reviewed here to highlight the conserved vs. variable aspects of hindbrain organization contributing to diversification of efferent sub-nuclei. Recent studies of segmental origins and migrations of branchiomotor, visceromotor and octavolateral efferent neurons revealed more segmental similarities than differences among vertebrates. Nonetheless, discrete variations exist in the origins of trigeminal, abducens and glossopharyngeal efferent nuclei. Segmental variation of the abducens nucleus remains the sole example of efferent neuronal homeosis during vertebrate hindbrain evolution. Comparison of cranial efferent segmental variations with surrounding intrinsic neurons will distinguish evolutionary changes in segment identity from lesser transformations in expression of unique neuronal types. The diversification of motoneuronal subgroups serving new muscles and functions appears to occur primarily by elaboration within and migration from already established segmental efferent pools rather than by de novo specification in different segmental locations. Identifying subtle variations in segment-specific neuronal phenotypes requires studies of cranial efferent organization within highly diverse groups such as teleosts and mammals.

Animals↗

Appropriate use of antitussives and protussives. A practical review.

As a symptom of an underlying condition, cough is one of the most common reasons patients see physicians. To the majority, a cough means that 'something is wrong' and it causes exhaustion and/or self-consciousness. Patients find these reasons as well as effects on lifestyle, fear of cancer and/or AIDS or tuberculosis to be the most troublesome concerns for which they seek medical attention. The treatment of cough can be divided into two main categories: (a) therapy that controls, prevents or eliminates cough (i.e. antitussive); and (b) therapy that makes cough more effective (i.e. protussive). Antitussive therapy can be either specific or nonspecific. Definitive or specific antitussive therapy depends on determining the aetiology or operant pathophysiological mechanism, and then initiating specific treatment. Since the cause of chronic cough can almost always be determined, it is possible to prescribe specific therapy that can be almost uniformly successful. Non-specific antitussive therapy is directed at the symptom; it is indicated when definitive therapy cannot be given. Practically speaking, the efficacy of nonspecific therapy must be evaluated in double-blind, placebo-controlled, randomised studies of pathological cough in humans. Such studies have demonstrated the efficacy of dextromethorphan, codeine and ipratropium bromide aerosol in patients with chronic bronchitis. While the preferred treatment for patients with cough due to angiotensin converting enzyme (ACE) inhibitor therapy is withdrawal of the offending drugs, it may be possible to ameliorate the cough by adding nifedipine, sulindac or indomethacin to the treatment regimen. The efficacy of protussive therapy has not been well documented. Although hypertonic saline aerosol and erdosteine in patients with bronchitis, and amiloride aerosol in patients with cystic fibrosis have been shown to improve mucus clearance, their clinical utility has not been adequately studied.

Afferent Pathways↗

In-phase chest wall vibration decreases dyspnea during arm elevation in chronic obstructive pulmonary disease patients.

In-phase chest wall vibration (IPV) is known to decrease dyspnea in patients with chronic obstructive pulmonary disease (COPD) at rest and during leg exercise. In the present study, the effects of IPV (100 Hz) on dyspnea and arm fatigue during upper extremity activity were studied in 9 patients with COPD (mean FEV1, 0.95 l). Dyspnea and arm fatigue (modified Borg scale) and ventilatory variables were measured during arm elevation (AE) with weights lifted straight above the head with and without IPV. Mean dyspnea during AE was 3.3 without IPV and 2.1 with IPV (p<0.05), but, arm fatigue, oxygen saturation and end-tidal FCO2 were not affected by IPV. Minute ventilation during AE was significantly increased with IPV in 5 of 9 patients. The results suggest that IPV decreases dyspnea during AE.

Afferent Pathways↗

Gustatory signal processing in the glossopharyngeo-hypoglossal reflex arc of the frog.

The relationship between the gustatory input and motor output in the glossopharyngeo-hypoglossal reflex was analyzed on the basis of neuronal activities in the solitary tract and hypoglossal motor nuclei of bullfrogs. Concentration-response relations for NaCl, quinine and acetic acid, obtained from the glossopharyngeal (IXth) nerve and simultaneously recorded from the hypoglossal (XIIth) nerve, were expressed relative to the response of each nerve to 1 M NaCl. Compared with a relatively small amount of the afferent input for acid, the reflex motor output was much larger in the relative value. A similarly high output relation was obtained for warmed saline but not for quinine and cooled saline. Although the responsiveness of the nucleus tractus solitarius neurons to 1 M NaCl and 1 mM quinine was not significantly different from that of the hypoglossal motoneurons, responses to 10 mM acetic acid were greater in the latter neurons than in the former by a factor of about 5.2. These phenomena were consistent with those in the peripheral nerves. The solitary tract neurons responsive to NaCl, quinine and acid showed both the phasic and tonic components of discharges. According to classification by a transiency index, the discharge mode became more phasic for the hypoglossal motoneurons responsive to NaCl and quinine, but more tonic for those responsive to acid. The above-mentioned chemoreflex is thus regulated by the intrinsic neural network which sends signals to the XIIth nerve after modifying not only the amount but also the temporal pattern of gustatory nerve signals for a particular taste.

Afferent Pathways↗

Effect of lidocaine injection of EOAE in patients with tinnitus.

In the present study, evoked otoacoustic emissions (EOAEs) were measured in 30 patients with tinnitus before and after intravenous lidocaine injection (1 mg/kg). For EOAE recordings, 1 kHz tone burst stimuli were used. Intravenous lidocaine injection resulted in suppression of tinnitus in 22 (73%) ears, and changes of EOAE amplitude (increase or decrease) in 18 (60%) ears. Of the 18 ears with EOAE amplitude changes, tinnitus disappeared or decreased in 17 (94%) ears. In 12 ears without changes of EOAE amplitude, tinnitus was suppressed in only 5 (42%). Changes in latency were not detected in any of the ears. These results indicate that there is a relationship between the effect of lidocaine in tinnitus suppression and changes in cochlear micromechanics caused by lidocaine.

Acoustic Stimulation↗

Projections of the median raphe nucleus in the rat.

No previous report in any species has examined comprehensively the projections of the median raphe (MR) nucleus with modern tracing techniques. The present report represents an in depth analysis of the projections of MR by use of the anterograde anatomical tracer Phaseolus vulgaris-leucoagglutinin. MR fibers descend along the midline within the brainstem and mainly ascend within the medial forebrain bundle in the forebrain. MR fibers distribute densely to the following brainstem/forebrain sites: caudal raphe nuclei, laterodorsal tegmental nucleus, dorsal raphe nucleus, interpeduncular nucleus, medial mammillary body, supramammillary nucleus, posterior nucleus and perifornical region of the hypothalamus, midline and intralaminar nuclei of thalamus, dopamine-containing cell region of medial zona incerta, lateral habenula, horizontal and vertical limbs of the diagonal band nuclei, medial septum, and hippocampal formation. Virtually all of these structures lie on or close to the midline, indicating that the MR represents a midline/para-midline system of projections. Overall, MR projections to the cortex are light. MR projects moderately to the perirhinal, entorhinal and frontal cortices, but sparingly to remaining regions of cortex. A comparison of MR with dorsal raphe (DR) projections (Vertes RP. 1991. J Comp Neurol 313:643-668) shows that these two major serotonin-containing cell groups of the midbrain distribute to essentially nonoverlapping regions of the forebrain; that is, the MR and DR project to complementary sites in the forebrain. A direct role for the MR in the desynchronization of the electroencephalographic activity of the hippocampus and its possible consequences for memory-associated functions of the hippocampus is discussed.

Afferent Pathways↗

Role of hepatic, intrahepatic and hepatoenteral nerves in the regulation of carbohydrate metabolism and hemodynamics of the liver and intestine.

The liver as an effector organ is the major glucose reservoir, the utilization of which is controlled by hormones but also by hepatic sympathetic nerves. The liver as a sensory organ detects a glucose concentration gradient between the hepatic artery and the portal vein by intrahepatic sensory-effector nerves, generating a cholinergic signal for an insulin-dependent net hepatic glucose uptake. The liver senses the insulin concentration by hepatoenteral sensory-effector nerves, generating a cholinergic signal to increase glucose absorption in the intestine and thus its coordinated utilization in liver, muscle and adipose tissue.

Afferent Pathways↗

Effect of tachykinins on ascending and descending reflex pathway in rat small intestine.

AIM: To examine the effect of tachykinins on the ascending reflex pathway in rat small intestine, we used different selective neurokinin (NK) receptor antagonists (RA): a) NK1-RA: GR-82334 and CP-96.345, b) NK2-RA: MEN-10.376 and L-659.877. The aim was further to investigate the effect of substance P (SP) on the ascending excitatory and descending inhibitory reflex pathway. METHODS: The whole segments of rat ileum (10 cm in length) were studied in an organ bath. Ascending contraction of circle muscle was elicited by anal electrical stimulation (3 Hz, 1 ms, 20 V) and measured as change of intraluminal pressure by a perfused manometric system 2 cm and 4 cm orad of the stimulation site. RESULTS: GR-82334 and CP-96.345 (NK1-RA) caused a significant dose-related inhibition of the oral contraction at a distance of 4 cm: GR-82334 [area: -10 % +/- 8 % (10 nmol/L); -29 % +/ -10 % (1000 nmol/L). P < 0.05, n = 10], CP-96.345 [area: -2 %+/- 6 %(0.1 nmol/L); -14 % +/- 10 % (10 nmol/L). P < 0.01, n = 8], whereas the contractile response at a distance of 2 cm was unaltered (n = 8). In contrast, MEN-10.376 and L-659.877 (NK2-RA) did not alter the amplitude or the area under the curve (n = 10). Neither the NK1- nor the NK2-receptor antagonists had a significant effect on the latency of the reflex response. SP showed a significant increase in the ascending contraction and the descending relaxation (n = 6, P < 0.01). CONCLUSION: These results demonstrate that blockade of NK1-receptors decreases the oral reflex response. Latency of the reflex response remains unchanged, indicating that the effect is not due to an action on interneurons. NK2-receptors do not take part in the ascending reflex in rat small intestine. SP increases the descending relaxant reflex response and ascending contraction.

Afferent Pathways↗

[Compound EPSPs and action potential of mauthner cell evoked by skin stimulation in crucian carp].

OBJECTIVE: To investigate the effects of afferent excitatory inputs from skin on the excitability of Mauthner cell (M cell) of crucian carp. METHODS: Multiple-site intracellular recordings on the soma and the ventral dendrite (VD) of M cell and direct current stimulation on the skin surface of the fish's trunk were employed. RESULTS: Direct stimulation of the skin evoked 3 groups of compound excitatory postsynaptic potentials (EPSPs) on soma and VD of M cell. Group a EPSP had the lowest amplitude (< or = 0.35 mV), which was insensitive to high-frequency stimulation. It had the shortest latency (mean 1.9 ms) and could be recorded on the soma and the proximal end of VD. Group b EPSP had the highest amplitude (< or = 9.7 mV), which was increased when the recording electrode was moved from the soma to the distal end of VD. The latency of Group b (mean 4.5 ms) was shorter than that of Group c, but longer than that of Group a. We firstly found that action potential could be induced on the basis of Group b in M cell by skin stimulation. Group c EPSP was our new finding, which could only be evoked by higher intensity (noxious) stimulus (> or = 100 V). It had the longest latency (mean 13.5 ms) with amplitude between those of a and b, and was very sensitive to high frequency stimulation. All the three groups of EPSPs were superimposed with spike-like transient potentials, which were believed to be the sign of electrical synapse activities. CONCLUSIONS: (1) Action potential can be induced on M cell by skin stimulation, which is in controversy with previous reports; (2) the noxious skin stimulation can induce a late EPSP (Group c) in M cell; (3) the neural pathway projecting from skin to M cell is composed of a set of neuronal chains with different number of synaptic relays, in which short chains projected concentrically to the soma and the proximal part of VD, while long chains projected mainly to the distal part of VD; (4) both electrical and chemical synapses may exist in short and long pathways.

Afferent Pathways↗

Responses of neuromuscular systems under gravity or microgravity environment.

Hindlimb suspension of rats induces induces fiber atrophy and type shift of muscle fibers. In contrast, there is no change in the cell size or oxidative enzyme activity of spinal motoneurons innervating muscle fibers. Growth-related increases in the cell size of muscle fibers and their spinal motoneurons are inhibited by hindlimb suspension. Exposure to microgravity induces atrophy of fibers (especially slow-twitch fibers) and shift of fibers from slow- to fast-twitch type in skeletal muscles (especially slow, anti-gravity muscles). In addition, a decrease in the oxidative enzyme activity of spinal motoneurons innervating slow-twitch fibers and of sensory neurons in the dorsal root ganglion is observed following exposure to microgravity. It is concluded that neuromuscular activities are important for maintaining metabolism and function of neuromuscular systems at an early postnatal development and that gravity effects both efferent and afferent neural pathways.

Afferent Pathways↗

[The cervical somatosensory evoked potential and its relation to F-wave activity].

In 6 healthy volunteers aged 18-25 years cervical somatosensory evoked potentials (CEPs) were recorded following stimulation of the right median nerve at the wrist. At the same time the antidromically elicited individual F-waves evoked by any single impulse were recorded from the abductor pollicis brevis muscle. By means of selective averaging of the neck responses it could be shown that there was a close relationship between an F-wave-activity of 120-150 microV/stimulus or more during the trial and the appearance or the enhancement of a negative peak occurring 0.5-1.4 ms after the main CEP component N13. An F-wave-activity of more than 224 microV/stimulus regularly resulted in a total change of the CEP configuration.

Adolescent↗

Features of entrainment of spinal pattern generators for locomotor activity in the lamprey spinal cord.

The in vitro lamprey spinal cord contains a "central pattern generator" (CPG) that can generate locomotor activity with excitatory amino acids added to the bath. The motor pattern can be entrained by imposed rhythmic bending of either the caudal or rostral end of the notochord/spinal cord. In the present study, the quantitative and mechanistic features of entrainment were investigated. Increasing the amplitude of the imposed movement increased the range of frequencies over which entrainment occurred. Brief, pulsed, imposed movements could reset the locomotor rhythm. During entrainment at different imposed movement frequencies, the burst duration was a constant proportion of about 35% of the cycle time. The intersegmental phase lag, which is usually constant at about 0.01 during locomotion, decreased significantly with caudal imposed movements. A small increase in the phase lags was observed with rostral imposed movements. In low-calcium Ringer's, briefly bending the notochord/spinal cord activated intraspinal mechanoreceptors and elicited ascending and descending unit activity in lateral spinal fascicles many segments from the point of bending. However, this ascending or descending movement-related activity was insufficient to fully entrain the locomotor rhythm, since blocking the pattern in the region of bending abolished 1:1 entrainment. The mechanoreceptors appear to act locally on the CPG networks, since interrupting the ascending or descending movement-related activity with lesions of the lateral fascicles did not abolish entrainment. In contrast, stripping the very lateral margins of the spinal cord in the region of bending did abolish entrainment, presumably by destroying the transduction region of the mechanoreceptors. The data, taken together, suggest that the mechanoreceptors entrain the local CPG networks, and this timing information is then distributed to the other parts of the spinal motor networks through the coordinating system.

Afferent Pathways↗