Characteristics of synaptic responses of motoneurons to ventrolateral funiculus stimulation in vitro]

Twenty 3-6-week-old Merino lambs were given either 3, 1 or 0 treatments of 50 microg oestradiol benzoate and (48 h later) a 1.5 mg Norgestamet implant left in situ for 9 days (3-, 1- and 0CYCLE+G). On Day 7 after the last implant insertion, and on the same day for 0CYCLE+G, each lamb received 400 I.U. pregnant mare serum gonadotrophin and 6 mg follicle-stimulating hormone (FSH). The reproductive tracts were removed for oocyte collection 24 h after FSH. Reproductive tracts were also collected from 16-24-week-old lambs (n = 31) (0CYCLE-G). The number of antral follicles per ovary was similar for the 3-, 1- and 0CYCLE+G treatments. Similar rates of in vitro maturation and monospermic fertilization were obtained for all groups. The proportion of blastocysts per cleaved oocyte was higher for 1CYCLE+G (50.5%) than for 3CYCLE+G (32.9%), 0CYCLE+G (24.3%), and 0CYCLE-G (11.8%) (P < 0.05). Viable fetuses were obtained at Day 93 of pregnancy after transfer of embryos from all treatments. These results indicate that a single treatment with oestrogen and progesterone, prior to gonadotrophin stimulation, will increase the yield and developmental capacity of oocytes from prepubertal sheep.     

Chemical stimulation of the intracranial dura induces enhanced responses to facial stimulation in brain stem trigeminal neurons

Chemical activation and sensitization of trigeminal primary afferent neurons innervating the intracranial meninges have been postulated as possible causes of certain headaches. This sensitization, however, cannot explain the extracranial hypersensitivity that often accompanies headache. The goal of this study was to test the hypothesis that chemical activation and sensitization of meningeal sensory neurons can lead to activation and sensitization of central trigeminal neurons that receive convergent input from the dura and skin. This hypothesis was investigated by recording changes in the responsiveness of 23 [16 wide-dynamic range (WDR), 5 high threshold (HT), and 2 low threshold (LT)] dura-sensitive neurons in nucleus caudalis to mechanical stimulation of their dural receptive fields and to mechanical and thermal stimulation of their cutaneous receptive fields after local application of inflammatory mediators or acidic agents to the dura. Responses to brief chemical stimulation were recorded in 70% of the neurons; most were short, lasting the duration of the stimulus only. Twenty minutes after chemical stimulation of the dura, the following changes occurred: 1) 95% of the neurons showed significant increases in sensitivity to mechanical indentation of the dura: their thresholds to dural indentation changed from 1.57 to 0.49 g (means, P < 0.0001), and the response magnitude to identical stimuli increased by two- to fourfold; 2) 80% of the neurons showed significant increases in cutaneous mechanosensitivity: their responses to brush and pressure increased 2.5- (P < 0.05) and 1. 6-fold (P < 0.05), respectively; 3) 75% of the neurons showed a significant increase in cutaneous thermosensitivity: their thresholds to slow heating of the skin changed from 43.7 +/- 0.7 to 40.3 +/- 0.7 degrees C (P < 0.005) and to slow cooling from 23.7 +/- 3.3 to 29.2 +/- 1.8 degrees C (P < 0.05); 4) dural receptive fields expanded within 30 min and cutaneous receptive fields within 2-4 h; and 5) ongoing activity developed in WDR and HT but not in LT neurons. Application of lidocaine to the dura abolished the response to dural stimulation but had minimal effect on the increased responses to cutaneous stimulation (suggesting involvement of a central mechanism in maintaining the sensitized state). Antidromic activation (current of <30 muA) of dura-sensitive neurons revealed projections to the hypothalamus, thalamus, and midbrain. These findings suggest that chemical activation and sensitization of dura-sensitive peripheral nociceptors could lead to enhanced responses in central neurons and that this central sensitization therefore could result in extracranial tenderness (mechanical and thermal allodynia) in the absence of extracranial pathology. The projection targets of these neurons suggest a possible role in mediating the autonomic, endocrine, and affective symptoms that accompany headaches.     

Visceral pain: responses of the reticular formation neurons to gallbladder distension

Visceral projection (gallbladder distension) to the gigantocellular nucleus of the reticular formation of the cat was tested in neurons classified as pain (P), nonpain-pain (NP-P) and nonpain (NP) units, according to their responses to noxious and/or innocuous natural stimuli from the somatic areas. 96% of P neurons (23 out of 24) responded to gallbladder distension. Quantitative criteria showed comparable effectiveness of the somatic and visceral inputs. NP-P neurons reacted to the gallbladder stimulation in 71% of cases (22 out of 31); NP neurons were activated less effectively. Stimulation of either the central tegmental field or "nonspecific" thalamic nuclei evoked direct responses in 38% of P and 26% of NP-P units, which, in most of the P neurons were followed by excitatory and inhibitory phases. The duration of the latter was approximately one second and it greatly affected the responses of the units to somatic as well as to visceral inputs. A large proportion of P neurons responding to a visceral input documents the important role of the reticular formation in the mechanisms of visceral pain. Findings concerning comparable modifying influences upon reactions of P units both in the case of visceral and painful somatic afferentation indicated that similar control mechanisms could be involved.     

Brain stem auditory-evoked responses in suspected central pontine myelinolysis

Central pontine myelinolysis was suspected in two chronic alcoholics who developed and recovered from a progressive spastic paresis of all muscles, that derived innervation at and below the level of the pons. In both cases, short-latency auditory-evoked responses aided in the diagnosis by indicating a slowing of conduction in the pontine auditory pathway, which varied in degree with the severity of the clinical manifestations of pontine demyelination.     

Effects of stimulation of the midbrain reticular formation upon thalamo-cortical neurones responsible for cortical recruiting responses

1. In lightly nembutalized cats, effects of high frequency (60-100/sec) repetitive stimulation of the midbrain reticular formation (RF) were tested upon the thalamo-cortical (T-C) neurones which project from the anterior ventral (VA) nucleus of the thalamus and its vicinities to the parietal association cortex and convey impulses responsible for cortical recruiting and spindling-like responses. 2. Tonic maintained or rhythmic grouped firings of the T-C neurones recorded as extracellular units with microelectrode in the thalamus were in the majority suppressed by high frequency RF stimulation during and often for a short time after the stimulation, and they showed later tonic discharges for many seconds or minutes. Intracellular recording from the T-C neurones revealed hyperpolarizing potential changes corresponding to the suppression on high frequency RF stimulation. Field potential analysis in the VA nucleus indicated that the hyperpolarization is ascribed at least in part to IPSPs elicited in the T-C neurones. Responses in some other types of thalamic neurones to the RF stimulation were exemplified to be compared and related with those of the T-C neurones. 3. Desynchronization of the parietal electrocorticogram coincided with the suppression of the T-C neurones and lasted for the time of the later tonic discharges, which contrasted with the rhythmic grouped discharges of the T-C neurones in association with recruiting and spindling-like responses of the cortex. Relations between the thalamo-cortical recruiting system and the ascending reticular activating system were discussed.     

Brain stem auditory evoked potentials from bone stimulation in dogs

Brain stem auditory evoked potential (BAEP) testing with air-conducted click stimuli can be used to diagnose sensorineural deafness in dogs if conductive deafness can be ruled out. Detection of conductive deafness can be performed by recording BAEP elicited by a vibratory stimulus transducer placed against the skull. Air- and bone-conducted BAEP were compared in dogs, varying bone stimulator placement, click polarity, and stimulus intensity. Optimal bone stimulator placement was determined to be over the mastoid process, followed by the mandible and the zygomatic arch. Condensation polarity clicks gave responses preferable to those elicited by rarefaction or alternating polarity. Bone-conducted BAEP peak latencies were significantly longer than air-conducted latencies after correction of the latencies for the air conduction time accompanying air-conducted stimuli. Significant differences between stimulus modalities were not seen for BAEP peak amplitudes or interpeak latencies. Latency-intensity and amplitude-intensity regressions had similar effects for both modalities: latencies decreased and amplitudes increased as stimulus intensity increased.     

Brain stem reticular formation neuronal correlates of stimulus significance and behavior during discriminative avoidance conditioning in rabbits.

Recorded multiple-unit activity in the reticular formation (RF) of the midbrain and pons in 14 New Zealand white rabbits during discriminative conditioning of locomotor (wheel-running) avoidance behavior, to examine whether discriminative neuronal activity develops in the RF during discriminative avoidance conditioning, and, if so, what its relation is to the activity in the limbic cortical structures and to the behavior. The positive and negative conditional stimuli (CS+ and CS–) were pure tones of different auditory frequency, and the unconditioned stimulus/stimuli (UCS) was a constant-current footshock (1.5–2.5 mA) delivered through the grid floor of the wheel. The pontine, but not the midbrain, sites manifested development during behavioral acquisition, of brief-latency (10–40 msec) discriminative neuronal discharges (i.e., greater discharges to the CS+ than to the CS–). The greatest magnitude of the discriminative discharges in the rostral pontine loci occurred in the 1st conditioning session. The discriminative response in the caudal loci developed more slowly, and it persisted to the criterial stage of training. Both rostral and caudal pontine loci, during the interval from CS onset to UCS onset, manifested a progressive build-up of neuronal firing in anticipation of the behavioral response. (59 ref) (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Physiological identification and analysis of dentate granule cell responses to stimulation of the medial and lateral perforant pathways in the rat

Stimulation of the dorsomedial or ventrolateral perforant pathways resulted in quantitatively different extracellularly recorded EPSPs in the fascia dentata of the rat. The two potentials differed in latency to peak and in width at half amplitude in a manner consistent with the different locus of termination of the two pathways on the granule cell dendrites. Both potentials were able to follow brief stimulus trains of 100 Hz, which suggests that they are monosynaptic. Medially elicited responses had their peak negativity approximately 100 to 180 micrometer deeper in the molecular layer than laterally elicited responses. Stimulation at short intervals along a dorsomedial to ventrolateral track in the angular bundle yielded a step function rather than a continuum of EPSP peak latency and half-width, in agreement with Hjorth-Simonsen's ('72) evidence for the separateness of the two pathways. Both pathways were able to induce granule cell discharge. Laterally elicited spikes, however, were delayed. Stimulation at intermediate locations frequently elicited double spikes from the granule cell population. Population spikes elicited by either pathway were inhibited for as long as 100 msec after a single discharge. Both pathways showed facilitation with double stimuli at short intervals, and both showed post-tetanic potentiation lasting at least 30 minutes. Under conditions where it could be shown that the two pathways at least partially converged onto the same granule cells, the response of one pathway did not increase when long lasting potentiation was induced on the other.     

Changes in responses of medial pontomedullary reticular neurons during repetitive cutaneous, vestibular, cortical, and tectal stimulation

1. In cats anesthetized with chloralose, responses of medial pontomedullary reticular neurons to stimulation of the body surface, vestibular nerves, superior colliculi, pericruciate cortices, cerebral peduncles, and spinal cord were studied at different stimulus rates. Raising the rate from 1/10 s to between 1/4 s and 2/s caused a significant decrement or increment in the response of most neurons tested. Response decrement typically began near the beginning of the higher frequency stimulus sequence and increased throughout the sequence. Response increment usually began somewhat later, rose to a peak, and then declined. Recovery from response decrement or increment usually occurred within 30-60 s at a 1/10 s stimulus rate.2. Measurements of response latency and of changes occurring in the initial and longer latency portions of responses indicated that all components of a response typically decreased or increased in parallel. Background spontaneous activity did not change during response decrements, but sometimes increased during response increment.3. Where changes could be detected, response decrement usually developed more rapidly when a sequence of repetitive stimulation was repeated.4. Response decrement was most pronounced at the highest stimulation rates and lowest stimulus intensities. Response increment was usually maximal at a stimulus rate of 1/s: at lower rates less increment occurred; at higher rates responses began to exhibit decrement.5. Response changes varied with the type of stimulus applied. Response decrements predominated when the body surface, vestibular nerves, or ipsilateral superior colliculus were stimulated. Approximately equal amounts of response increment and decrement were produced by repetitive stimulation of the cerebral peduncles and contralateral superior colliculus. Stimulation of the surface of the pericruciate cortex or of the spinal cord usually produced a long-lasting response increment.6. Generalization of response decrement and increment was observed in cases where trains of stimuli at a rate of 2/s applied to one point produced changes in the response to stimulation of another point which was tested once per 10 s and where single-shock stimulation of the first point was without effect on the test response. Generalization of response decrement occurred most often when two nearby points were stimulated. Generalization of response increment appeared to spread widely between distant cutaneous points and stimuli of different kinds.7. The response decrement and increment observed in medial pontomedullary reticular neurons displayed most of the parametric features of behavioral habituation and sensitization (8, 33) and therefore appear to represent neural analogs of these latter phenomena. The properties of response decrement suggest that it may occur to a large extent within afferent pathways leading to medial reticular neurons...     

Medullary pathways of cardiovascular responses to 5-HT2 and 5-HT3 receptor stimulation in the rat nucleus tractus solitarius

As previously found for the baroreceptor reflex, microinjection of kynurenic acid (KYN, 2 nmol), a glutamate receptor antagonist, into the caudal ventrolateral medulla (CVL) blocked the hypotension and bradycardia elicited by microinjections of a 5-HT2 receptor agonist, 2,5-dimethoxy-4-iodoamphetamine (DOI, 0.5 pmol) into the nucleus tractus solitarius (NTS). In addition, as previously observed with the sympathetic chemoreflex response, microinjections of KYN into the RVI, blocked the increase in blood pressure elicited by microinjections of 1-m-(chlorophenyl)-biguanide (1200 pmol), a 5-HT1 receptor agonist, into the NTS. These results suggest that medullary pathways involved in the responses to 5-HT2 and 5-HT3 receptor stimulation in the NTS are similar to those that mediate the baroceptor and chemoreceptor reflex responses, respectively.     

Development of glycinergic synaptic transmission to rat brain stem motoneurons

Using an in vitro rat brain stem slice preparation, we examined the postnatal changes in glycinergic inhibitory postsynaptic currents (IPSCs) and passive membrane properties that underlie a developmental change in inhibitory postsynaptic potentials (IPSPs) recorded in hypoglossal motoneurons (HMs). Motoneurons were placed in three age groups: neonate (P0-3), intermediate (P5-8), and juvenile (P10-18). During the first two postnatal weeks, the decay time course of both unitary evoked IPSCs [mean decay time constant, taudecay = 17.0 +/- 1.6 (SE) ms in neonates and 5.5 +/- 0.4 ms in juveniles] and spontaneous miniature IPSCs (taudecay = 14.2 +/- 2.4 ms in neonates and 6.3 +/- 0.7 ms in juveniles) became faster. As glycine uptake does not influence IPSC time course at any postnatal age, this change most likely results from a developmental alteration in glycine receptor (GlyR) subunit composition. We found that expression of fetal (alpha2) GlyR subunit mRNA decreased, whereas expression of adult (alpha1) GlyR subunit mRNA increased postnatally. Single GlyR-channels recorded in outside-out patches excised from neonate motoneurons had longer mean burst durations than those from juveniles (18.3 vs. 11.1 ms). Concurrently, HM input resistance (RN) and membrane time constant (taum) decreased (RN from 153 +/- 12 MOmega to 63 +/- 7 MOmega and taum from 21.5 +/- 2.7 ms to 9.1 +/- 1.0 ms, neonates and juveniles, respectively), and the time course of unitary evoked IPSPs also became faster (taudecay = 22.4 +/- 1.8 and 7.7 +/- 0.9 ms, neonates vs. juveniles, respectively). Simulated synaptic currents were used to probe more closely the interaction between IPSC time course and taum, and these simulations demonstrated that IPSP duration was reduced as a consequence of postnatal changes in both the kinetics of the underlying GlyR channel and the membrane properties that transform the IPSC into a postsynaptic potential. Additionally, gramicidin perforated-patch recordings of glycine-evoked currents reveal a postnatal change in reversal potential, which is shifted from -37 to -73 mV during this same period. Glycinergic PSPs are therefore depolarizing and prolonged in neonate HMs and become faster and hyperpolarizing during the first two postnatal weeks.     

Responses of human single motor units to transcranial magnetic stimulation

The authors analyse the results of 51 unicompartmental knee prostheses with 1 to 12 years follow-up (mean follow-up: 5 years). The results were evaluated using the scoring system of the "Knee Group" of the SO.B.C.O.T. (Société Belge de Chirurgie Orthopédique et de Traumatologie). This analysis demonstrates that the quality of the results depends on implant positioning. The authors suggest positioning the tibial implant parallel with the healthy plateau and slightly distal, i.e. to position the tibial implant perpendicular to the epiphyseal axis and not to the mechanical axis, as is systematically done with the usual tibial cutting guides. When this ideal positioning was respected, 77.5% of the patients had a score above 90 points (out of a possible maximum of 100 points) and 12.5% had a score between 75 and 89 points. When this condition was not respected, none of the knees obtained more than 75 points. The difference was statistically significant (p = 0.0001).     

Classical conditioning of the rabbit eyelid response with a mossy-fiber stimulation CS: II. Lateral reticular nucleus stimulation.

Stimulation of mossy fibers arising from the pontine nuclei can be used as a conditioned stimulus (CS) during classical conditioning of the eyelid/nictitating membrane response (NM). In the present experiment we stimulated another source of mossy fibers, the lateral reticular nucleus (LRN), as a CS for NM conditioning. LRN stimulation was an effective CS, resulting in learning, and the conditioned response to LRN stimulation showed normal extinction. Unpaired presentation of CS and US did not result in pseudo-conditioning. Lesions of the cerebellar dentate-interpositus region abolished the conditioned response but left the unconditioned reflex response intact. We suggest that mossy fibers may normally carry CS information to the cerebellum. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Motor units within the normal rat medial gastrocnemius

The contractile properties, fatiguability and axonal conduction velocity were determined for 118 motor units in the medial gastrocnemius of eighteen rats. Fast-twitch and slow-twitch units could be categorized on the basis of the 'sag' test. For the purposes of statistical comparison the fast-twitch units were classified on the basis of their fatiguability as fast-fatiguable (FF), fast intermediate (FI) and fast fatigue-resistant (FR). As such, FR units tended to have a longer isometric twitch time course than other fast-twitch units. On the basis of peak tetanic force FF units were largest (mean 341 +/- 120 mN) followed by FI (145 +/- 85 mN), FR (87.3 +/- 38) and slow units (40.4 +/- 11.0 mN). There were no differences in motor axonal conduction velocity. Although units were categorized, it is clear that for all characteristics investigated the fast-twitch units exist as a continuum. Some of the largest FF units (peak force 350-500 mN) failed to maintain force with high-frequency stimulation (300 Hz) and this was associated with a failure of the EMG signal.     

Mechanism of coronary microvascular responses to metabolic stimulation

Previous studies from our laboratory have shown that coronary microvascular dilation to increased myocardial oxygen consumption (MVO2) is greater in vessels < 100 microns. The mechanism responsible for this response is uncertain. OBJECTIVES: We tested the hypothesis that microvascular dilation to increased MVO2 is mediated by nitric oxide (NO). Since NO release may occur in response to increased shear, we also tested the hypothesis that metabolic byproducts released in response to increase in MVO2 will stimulate opening of the ATP-sensitive potassium channel. METHODS: Changes in epicardial coronary microvascular diameters were measured in 9 dogs given NG-nitro-L-arginine (LNNA; 100 microM, topically), 7 dogs given glibenclamide (10 microM, topically) and 12 control (C) dogs during increases in metabolic demand using dobutamine (DOB, 10 micrograms/kg/min, i.v.) with rapid atrial pacing (PAC, 300 bpm). Diameters of arterioles were measured using intravital microscopy coupled to stroboscopic epi-illumination. RESULTS: During the protocol, MVO2 increased to a similar degree in both experimental groups (LNNA and glibenclamide). Baseline hemodynamics and coronary microvascular diameters were similar between the two experimental groups and their respective control groups. In the presence of LNNA, coronary arteriolar (< 100 microns) dilation (% change from baseline) was impaired during the protocol (DOB: vehicle 18 +/- 5, LNNA 2 +/- 2 [P < 0.05]; DOB + RAP: vehicle 40 +/- 11, LNNA 6 +/- 2% [P < 0.05]). In contrast, glibenclamide did not impair coronary microvascular responses to increased MVO2 despite increases in MVO2. CONCLUSION: This study indicates that coronary microvascular dilation in response to increased metabolic stimulation using dobutamine in conjunction with rapid pacing is mediated through a nitric-oxide-dependent mechanism and not ATP-sensitive potassium channels. These results may have important implications in pathological disease states where nitric oxide mechanisms are impaired, such as diabetes and hypertension.     

Noradrenaline modulation of the responses of the cerebellar Purkinje cell to afferent synaptic activity

Freshly isolated fetal liver explants in organ culture did not convert L-[14C]alanine or L-[14C]lactate to carbohydrate, but L-[14C]serine and D-[14C]glycerol were both transformed. When explants were subjected to 42 hr of preliminary incubation without supplements, followed by transfer to fresh medium with added precursor, all four substrates underwent gluconeogenic transformation. It was concluded that the ability of fetal rat liver in organ culture to convert alanine and lactate to carbohydrate evolves slowly, but the conversion of glycerol, and to a lesser extent serine, to glucose and glycogen is initiated immediately.     

Costimulation pathways in host immune responses to allogeneic hepatocytes

BACKGROUND: This study investigated the role of the CD28/B7 (blocked by CTLA4Ig) and CD40/CD40L (blocked by MR1) costimulation pathways on in vivo host T-cell- mediated immune responses to allogeneic hepatocytes. METHODS: Survival of allogeneic hepatocytes (H-2q) in C57BL/6 (H-2b) mice untreated or treated with MR1, CTLA4Ig, L6 (control fusion protein), or a combination of MR1 and CTLA4Ig fusion protein was determined. RESULTS: Median survival time for hepatocellular allografts was 10, 84, 10, 10, and 84 days in untreated (n= 10), MR1-treated (n=7) (P<.0001), CTLA4Ig-treated (n=7) (P=0.02), L6-treated (n=3) (P, not significant), and the combination of MR1- and CTLA4Ig-treated (n=6) (P=0.0003) groups, respectively. CONCLUSIONS: Host treatment with MR1, but not CTLA4Ig, prolonged hepatocellular allograft survival. These data suggest that CD28/B7 interactions appear relatively unimportant, whereas CD40/CD40L interactions provide critical costimulator signals for T-cell-dependent immune responses to allogeneic hepatocytes.     

Cerebral evoked responses to gastrointestinal stimulation in humans

Recent advances have permitted recording of evoked potentials (EPs) in response to electrical and mechanical stimulation of the gastrointestinal (GI) organs via methods used primarily in clinical neurophysiology. Current research involving stimulation of the esophagus, rectum, and colon, and recording the corresponding responses on the scalp, is being practiced in only a few laboratories. This review examines the engineering aspects of recording EPs, such as characteristics of the stimuli, placement of stimulus electrodes in the GI tract, and enhancement of evoked potential signals. We also discuss the physiological concepts involved in the generation of EPs, and how these compare with somatosensory evoked responses. Current experimental techniques employed by various investigators and results reported from their laboratories are compared. We believe that cerebral EPs to GI stimulation could be useful in studying a number of pathophysiological conditions such as gastroesophageal reflux disease, diffuse esophageal spasm, chronic inflammatory bowel disorders, chronic abdominal pain, and irritable bowel syndrome, among others. We hope that the present review will generate interest in the use of EPs arising out of GI stimulation, aiding in understanding their physiological implications in healthy subjects and in GI disorders.