Isolation of cholinergic synaptic vesicles from the myenteric plexus of guinea-pig small intestine

The acetylcholine-rich myenteric plexus-longitudinal muscle preparation of the guinea-pig small intestine has been subjected to subcellular fractionation using modifications of both classical methods and that originally devised for bulk isolation of cholinergic synaptic vesicles from the electromotor nerve terminals of Torpedo marmorata by means of density gradient centrifugation in a zonal rotor. The latter method gave a vesicle fraction with the highest acetylcholine content so far recorded for a mammalian particulate fraction, 30.9 +/- S.E.M. 1.8 (5) nmol of acetylcholine . mg of protein-1. Electron-microscopical examination showed that it consisted of a homogeneous preparation of vesicles of mean spherical diameter 61 +/- SD 4 (108) nm, with little or no contamination with other lipoprotein membrane structures, mixed however with considerable amounts of actomyosin fibrils, presumably derived from the longitudinal muscle. Slab-gel electrophoresis in sodium dodecyl sulphate showed that, in addition to prominent peaks attributable to actin and myosin, there was a relatively simple pattern of (presumably) vesicle protein among which all the proteins thought to be characteristic of Torpedo synaptic vesicles were present.     

Quantitative analysis of inputs to somatostatin-immunoreactive descending interneurons in the myenteric plexus of the guinea-pig small intestine

An unusual case of bilateral inflammatory external/internal root resorption developed in the maxillae of a 28 year-old female approximately 4 years following routine segmental orthognathic surgery. The patient experienced dental pain in a tooth adjacent to a segmental osteotomy cut 8 months postsurgery, however, the tooth later became asymptomatic. A definitive diagnosis of inflammatory cervical root resorption was not established until nearly 4 years later on routine dental examination. The external/internal resorptive lesions were located 4 to 6 mm apical to the connective tissue attachment on 3 of the 4 tooth roots adjacent to osteotomy cuts. Two of the affected teeth required non-surgical root canal therapy due to pulpal communication with the resorptive defects. The lesions were accessed by flap surgery, thoroughly debrided, and obturated with an intermediate restorative material until definitive restorative therapy could be completed. All sites healed uneventfully and the patient has been closely observed for approximately 2 years without symptoms or recurrence of the resorptive lesions. Dental health care providers should be alert to the possible occurrence of inflammatory root resorption in sites adjacent to osteotomy cuts over extended periods of time. Routine radiographic examination may be beneficial in the postoperative management of the segmental orthognathic surgery patient.     

Stimulation-induced 3H-L-citrulline accumulation in isolated longitudinal muscle myenteric plexus preparations of rat small intestine: a measure to characterize nitrergic neurons

Nitric oxide (NO) synthase activity in rat isolated longitudinal muscle myenteric plexus preparations of the small intestine was determine by measuring the accumulation of 3H-L-citrulline during 30 min incubation with 3H-L-arginine. In untreated preparations a significant amount of 3H-L-citrulline accumulated in the tissue, about 2000 dpm/30 mg per 30 min, accounting for about 1.7% of the tissue radioactivity. Intermittent electrical field stimulation (15 Hz, 10 s trains with 10 s intervals for total of 20 min) caused a threefold increase in 3H-L-citrulline accumulation. The NO synthase inhibitor N omega-nitro-L-arginine methyl ester (L-NAME) reduced the spontaneous accumulation of 3H-L-citrulline by 65% and prevented the electrically evoked increase. Removal of extracellular calcium or addition of tetrodotoxin blocked the electrically evoked increase in 3H-L-citrulline accumulation without affecting spontaneous accumulation. Application of the calcium ionophore A 23187 (10 mumol/l) or 45 mmol/l) or 45 mmol/l potassium caused a twofold increase in the accumulation of 3H-L-citrulline. The muscarine receptor agonist oxotremorine (1 mumol/l) had no effect on spontaneous accumulation of 3H-L-citrulline, but inhibited the electrically evoked increase by about 50%, and this effect was blocked by scopolamine. A substantial amount of 3H-L-citrulline (15000 dpm) accumulated also in the incubation media, and this was increased 1.7-fold by the presence of A 23187 and 2.7-fold by electrical stimulation. However, electrically evoked increase in 3H-L-citrulline was not prevented by tetrodotoxin, in contrast to observation on tissue levels. In conclusion, during incubation with 3H-L-arginine tissue levels of 3H-L-citrulline in rat isolated longitudinal muscle myenteric plexus preparations, but not accumulation in incubation media may be used as a biochemical marker of the activity of nitrergic intestinal neurons which appear to be inhibited via muscarine receptors.     

Purinergic fast excitatory postsynaptic potentials in myenteric neurons of guinea pig: distribution and pharmacology

BACKGROUND & AIMS: Adenosine triphosphate (ATP) acting at P2 receptors mediates some fast excitatory postsynaptic potentials (fEPSPs) in myenteric neurons of guinea pig ileum. The present studies investigate the distribution of purinergic fEPSPs along the length of the gut and characterize the P2-receptor subtype mediating fEPSPs. METHODS: Conventional intracellular electrophysiological methods were used to record from myenteric neurons in vitro. RESULTS: At a membrane potential of -97 +/- 1 mV, the amplitude (25 +/- 1 mV; n = 307) of fEPSPs was similar along the gut. Hexamethonium (100 micromol/L) inhibited fEPSPs in the gastric corpus by 98% +/- 1% (n = 31) and in the duodenum, ileum, taenia coli, proximal colon, and distal colon by 42%-55%. In the presence of hexamethonium, suramin (100 micromol/L) or the P2X antagonist pyridoxal phosphate-6-azophenyl-2',4'-disulfonic acid (PPADS, 10 micromol/L) reduced the control fEPSP amplitude in the duodenum, ileum, taenia coli, proximal colon, and distal colon by 71%-84%. The pharmacology of the purinergic fEPSPs was investigated in detail in the ileum. Noncholinergic fEPSPs were concentration-dependently (1-30 micromol/L) inhibited by PPADS (50%-inhibitory concentration, 3 micromol/L). In addition, alpha,beta-methylene 5'-adenosine triphosphate (1 micromol/L) also reduced purinergic fEPSPs. CONCLUSIONS: Fast EPSPs mediated in part through P2X receptors are prominent in myenteric neurons along the small and large intestines but are rare in the gastric corpus.     

Endomorphin-1 and endomorphin-2 activate mu-opioid receptors in myenteric neurons of the guinea-pig small intestine

An association between hyperhomocysteinemia and premature atherosclerosis in patients with non-insulin-dependent diabetes mellitus (NIDDM) has recently been described. Little is known about the role of insulin in homocysteine [H(e)] metabolism. We measured plasma H(e) concentrations in the fasting state and during a hyperinsulinemic-euglycemic clamp in normal subjects and patients with NIDDM. Plasma H(e) decreased significantly from 7.2 +/- 2.6 to 6.0 +/- 2.7 mmol/L (P < .01) in normal subjects, but did not change in patients with NIDDM (6.0 +/- 2.7 to 5.9 +/- 2.5 mmol/L, respectively). These data suggest that plasma H(e) concentrations are regulated by acute hyperinsulinemia in normal subjects, but not in insulin-resistant NIDDM subjects. These abnormalities may have implications for the pathogenesis of premature vascular disease associated with NIDDM.     

Extrinsic denervation increases myenteric nitric oxide synthase-containing neurons and inhibitory neuromuscular transmission in guinea pig

Enteric nerves can function normally without connections with the central nervous system. A contributing component of the functional autonomy exhibited by enteric nerves is their plasticity. In the present study, the number of nitric oxide synthase-immunoreactive (NOS-ir) myenteric neurons and inhibitory neuromuscular transmission were studied in extrinsically denervated ileal segments. Segments of ileum were extrinsically denervated by crushing the mesenteric blood vessels supplying a loop of ileum in anesthetized guinea pigs. Some unoperated animals were treated with capsaicin or 6-hydroxydopamine (6-OHDA) to disrupt primary afferent and sympathetic nerves, respectively. NOS-ir was localized using indirect immunofluorescence. Nerve-mediated relaxations of longitudinal muscle were studied in vitro using standard methods. At 7 weeks after extrinsic denervation there was a 93% increase in the number of NOS-ir myenteric neurons. The number of neurons containing detectable vasoactive intestinal peptide-ir neurons was not changed after extrinsic denervation. Neurogenic relaxations caused by 10, 20 and 50 Hz transmural stimulation were larger in extrinsically-denervated tissues compared to control tissues. The NOS antagonist, nitro-L-arginine (300 microM) inhibited neurogenic relaxations in control and extrinsically-denervated tissues. Capsaicin- but not 6-OHDA-treatment mimicked the effects of extrinsic denervation on NOS-ir and neurogenic relaxations of the longitudinal muscle. Active or passive properties of the longitudinal muscle were unaffected by extrinsic denervation. These data indicate that extrinsic denervation is associated with an increase in the number of myenteric neurons expressing detectable NOS-ir and potentiation of inhibitory transmission to longitudinal muscle. This effect is due to loss of extrinsic sensory nerves.     

Relationship between muscarinic autoinhibition and the inhibitory effect of morphine on acetylcholine release from myenteric plexus of guinea pig ileum

A forthcoming draft Guidance of the Food and Drug Administration is expected to replace the current framework for the assessment of bioequivalence, based on the comparison of average kinetic responses, with a very different approach, the evaluation of individual bioequivalence. It emphasizes the estimation of intraindividual variances of the contrasted drug products as well as of the subject-formulation interaction, and requires the conduct of 4- (or 3-) period crossover bioequivalence trials. In order to facilitate the discussion of the draft Guidance and of the new approach, the underlying rationale, principles and procedures are described. Following this, various open questions are raised. It is suggested that their resolution should be carefully and widely discussed, and that more research and experience is needed before the possible implementation of the new approach.     

Projections of the estrogen receptor-immunoreactive ventrolateral hypothalamus to other estrogen receptor-immunoreactive sites in female guinea pig brain

The ventrolateral hypothalamus in female guinea pigs includes an estrogen receptor dense region adjacent to the ventromedial hypothalamus. This region is reciprocally connected with other estrogen receptor-containing areas suggesting that steroid hormone receptor-containing cells may be directly linked. Phaseolus vulgaris leucoagglutinin, an anterograde tract tracer, was specifically placed in this region with the aim of labeling some projections from estrogen receptor-containing neurons. These projections were colocalized immunocytochemically with the distribution of estrogen receptor-containing cells. Dense ventrolateral hypothalamic innervation was observed in some regions also containing a high concentration of estrogen receptor-containing cells. These regions included the medial preoptic area, the bed nucleus of the stria terminalis, the ventrolateral hypothalamus anterior and posterior to the injection site, and the midbrain central gray. A low density of ventrolateral hypothalamic fibers and terminals was observed in two regions rich in estrogen receptors, the amygdala and the arcuate nucleus. In general, ventrolateral hypothalamic fibers and terminals were present in all regions where estrogen receptors were found except the medial thalamus and habenular region. Labeled terminal boutons and perineuronal baskets were found around estrogen receptor-containing cells in most regions which contained estrogen receptor-containing cells. These close appositions were suggestive of synaptic contacts, suggesting that the ventrolateral hypothalamus may influence steroid-dependent behaviors via the modulation of estrogen receptor-containing cells. Furthermore, ventrolateral hypothalamic projections may include direct connections with estrogen receptor-containing cells, suggesting the presence of a network of interconnected estradiol-sensitive neurons involved in the regulation of estradiol-dependent functions.     

Esophageal aperistalsis secondary to metastatic invasion of the myenteric plexus

We have investigated the effects of four drugs on aspects of lipid metabolism in rats. The four drugs used were: tibric acid = 2-chloro-5-(cis--3,5-dimethylpiperidonosulfonyl)benzoic acid; DH 990 = 2-[(3,5-di-t-butyl-4-hy-droxyphenyl)thio]hexanoic acid; oxandrolone = 17beta-hydroxyphenyl-17a-methyl-2-oxa-5a-androstan-3-one; and Sch 9122=2-(p-anisyl)-3(2-pyridyl)pentane hydrochloride. Serum and liver triglycerides and liver cholesterol, 7a-hydroxylase and 26-oxidase were determined. Tibric acid (0.015%) was hepatomegalic and hypotriglyceridemic. It did not affect normal 7a-hydroxylase or 26-oxidase activity. In the absence of cytosal, this drug resulted in normal mitochondrial cholesterol-26-oxidase activity whereas none was observed with preparations from control rats. DH 990 (0.075%) did not affect liver size. It had a slight (10--20%) hypolipidemic effect. The effects of DH 990 on the two liver enzymes were similar to those of tibric acid. In view of the absence of a hepatomegalic effect of DH 990, its influence on mitochondrial oxidation of cholesterol in the absence of cytosol is noteworthy. Oxandrolone (0.15%) had a slight (11%) hepatomegalic effect but did not influence serum of liver lipid levels. This drug caused a 19% increase in liver 7a-hydroxylase activity but did not affect cholesterol-26-oxidase activity in the presence or absence of cytosol. Sch 9122 (0.03%) caused significant weight loss. Serum and liver cholesterol levels were unaffected, but serum triglyceride levels were significantly elevated in rats fed this drug. Cholesterol-7a-hydroxylase activity was slightly (11%) higher than normal, but 26-oxidase was significantly lower.     

The distribution of novel intermediate filament proteins defines subpopulations of myenteric neurons in rat intestine

BACKGROUND/AIMS: Recent studies with neurofilament antibodies as neuronal markers have shown subpopulations of myenteric neurons that do not contain neurofilament proteins. Novel neuronal intermediate filament proteins alpha-internexin, peripherin, and nestin have been identified. The aim of this study was to examine the distribution of these novel intermediate filaments in comparison with neurofilaments in myenteric plexus neurons. METHODS: Using indirect immunofluorescence techniques in whole-mount cryostat sections from neonate and adult rat small intestine and in primary cultures of myenteric neurons, the distribution of neurofilaments, alpha-internexin, peripherin, and nestin was studied in comparison with the neuronal marker protein gene product (PGP) 9.5 in myenteric neurons. RESULTS: Sixty-five percent of neurons contained neurofilament triplet proteins. alpha-Internexin and/or peripherin were found in the neurofilament-negative neurons. PGP 9.5 was present in 80% of the myenteric neurons. Of the neurons that were PGP negative, > 95% contained peripherin or alpha-internexin. Nestin was not found in either neonate or adult myenteric neurons but was seen in glial cells in culture. CONCLUSIONS: The results suggest that a subpopulation of myenteric neurons lacks neurofilament triplet proteins but contains either peripherin, alpha-internexin, or both. This selective distribution of intermediate filaments in subpopulations of enteric neurons may support differential roles in these structurally unique neurons.     

Morphological and quantitative analysis of the neurons of the myenteric plexus of the cecum of streptozotocin-induced diabetic rats

The purpose of this work was to study the neurons of the myenteric plexus of the cecum of rats with chronic streptozotocin-induced diabetes. We used four experimental groups of animals. In groups D2 and D8 animals were killed two and eight months, respectively, after diabetes induction and groups C2 and C8 were used as controls. We carried out whole-mount preparations stained with Giemsa and NADH-diaphorase. We verified that the diabetes did not alter the shape and disposition of the myenteric ganglia; it provoked decrease on the neuronal density and increase on the incidence of weakly basophilic neurons. The effects of streptozotocin caused dilatation of the cecum still evidenced two months after induction, but no more observed on the eight months after induction. The smaller incidence of neurons in group D8 relative to group C8 was due to the early loss related to the drug toxicity and later to the aging in diabetic condition.     

Effects of cortical stimulation on red nucleus neurons in the guinea pig

The aim of the present work was to study the control that the cerebral cortex exerts on red nucleus (RN) neurons in the guinea pig. The experiments were carried out in anaesthetized animals. Electrical stimulation of localized cortical foci was performed by tungsten microelectrodes in frontal and parietal regions containing sensorimotor representations of the body. Single unit RN activity was extracellularly recorded through glass micropipettes, and the encountered RN neurons were recognized by searching their peripheral receptive field. Then, corticorubral influences were tested on RN neurons whose receptive field was located in the same body regions where motor responses were evoked by cortical stimulation. The stimulation with a single pulse evoked complex responses, typically consisting of long lasting inhibitions sometimes preceded by a weak facilitation and always followed by an excitatory rebound. The application of a second pulse modified this pattern, depending on the time interval between the two stimuli. In fact, the reduction of the interval below 300 ms enhanced the excitatory components whereas it shortened the inhibitory component; moreover, an "early" facilitation was evoked but only at intervals as short as 50-150 ms, or less. These results suggest that the corticorubral control may vary according to different levels of cortical activation, becoming more and more facilitatory as the cortical discharges increase from low frequency values (tonic activity) towards high frequency values (phasic activity).     

Neurite outgrowth of striatal neurons in vitro: involvement of purines in the growth-promoting effect of myenteric plexus explants

We have shown previously that a soluble factor(s) released by the myenteric plexus promotes neurite outgrowth from postnatal striatal neurons, and that this effect was abolished by tetrodotoxin. We have now investigated the possible involvement of purines in the mediation of this neuritogenic response, by examining their effect on neurite length of striatal neurons both in co-culture with myenteric plexus explants and cultured alone. Both ATP and 2-chloroadenosine partially reversed the inhibitory effect of tetrodotoxin in co-cultures with whole myenteric plexus, while the stable ATP analogue, alpha, beta-methylene ATP, had no effect, suggesting that ATP was being broken down to adenosine before exerting its action. Further support for this view was that the ATP (P2) purinoceptor antagonist suramin did not reverse the effects of ATP, while the adenosine (P1) purinoceptor antagonist 8-(p-sulphophenyl)theophylline did antagonize the effects of ATP in tetrodotoxin-treated co-cultures. Further, both 8-(p-sulphophenyl)theophylline and adenosine deaminase reduced the effect of the myenteric plexus on striatal neurons in the absence of tetrodotoxin, and the adenylate cyclase activator forskolin completely reversed the effect of tetrodotoxin in our co-culture system. The neurite outgrowth-promoting effect of 2-chloroadenosine in tetrodotoxin-treated co-cultures was not further enhanced by a combination of neuropeptides. Serotonin and GTP were without effect on striatal neurons in the presence or absence of myenteric plexus explants. In experiments without myenteric plexus, both 2-chloroadenosine and forskolin caused a slight increase in striatal neurite length; ATP and GTP were ineffective. Basic fibroblast growth factor, nerve growth factor, neurotrophin-3 or neurotrophin-4/5 had no effect on neurite outgrowth in postnatal striatal cultures after two days in vitro. When these growth factors were added in combination with 2-chloroadenosine, the observed increase in mean neurite length did not exceed that induced by 2-chloroadenosine alone. Both 2-chloroadenosine and the ganglioside mix AGF1 increased neurite elongation of striatal neurons after two days in vitro, but an inhibition of enhanced neurite outgrowth was observed when both substances were added together. Both laminin and fibronectin were not neuritogenic for postnatal striatal neurons under our culture conditions. These observations suggest that a factor other than the growth factors tested here is involved in the promotion of striatal neurite outgrowth in co-culture with myenteric plexus explants. In summary, adenosine (probably acting through the A2 subclass of the P1 purinoceptor) leads to increased striatal neurite outgrowth in co-culture with myenteric plexus and we propose that it does so either (1) by triggering the release of a neuritogenic factor, possibly from enteric glial cells, or (2) by acting synergistically with such a growth factor. Adenosine acts via P1 purinoceptors, which leads to changes in cyclic AMP, and the response to forskolin suggests that cyclic AMP is probably involved in the events leading to increased striatal neurite outgrowth.     

Acoustic frequency tuning of neurons in the basal forebrain of the waking guinea pig

The acoustic responses of cells in the basal forebrain were studied in the adult waking guinea pig. Frequency receptive fields were obtained across wide frequency (0.094-45.0 kHz) and intensity (0-90 dB) ranges. A total of 326 recordings were obtained in 26 electrode penetrations from five subjects; 205 from the globus pallidus (GP), 98 from the caudate-putamen (CPu) and 23 from the central nucleus of the amygdala (ACE). Twenty-nine recordings exhibited acoustic responses (GP=20 (9.8%); CPu=9 (9.2%); ACE=0). Cells in the regions of the GP that project to the primary auditory cortex (ACx) exhibited frequency tuning that was dominantly suppressive. Responses in the CPu were excitatory, but poorly tuned. The spontaneous rate of discharge of GP cells that yielded complete tuning data was positively correlated with power in the beta bands (12-25 and 25-50 Hz) and negatively correlated with power in the delta band (1-4 Hz) of the EEG of the ACx. These findings suggest that acoustically tuned neurons in the GP that are inhibited by tones are involved in the regulation of auditory cortical state, possibly promoting deactivation to unimportant sounds, and may be cholinergic in nature.     

Single olivocochlear neurons in the guinea pig. II. Response plasticity due to noise conditioning

Previous studies have shown that daily, moderate-level sound exposure, or conditioning, can reduce injury from a subsequent high-level noise exposure. We tested the hypothesis that this conditioning produces an increased activity in the olivocochlear efferent reflex, a reflex known to provide protection to the cochlea. Guinea pigs were conditioned by a 10-day intermittent exposure to 2-4 kHz noise at 85 dB sound pressure level. This conditioning is known to reduce damage from a subsequent high-level exposure to the same noise band. Responses to monaural and binaural sound were recorded from single medial olivocochlear (MOC) efferent neurons, and data from conditioned animals were compared with those obtained from unexposed controls. MOC neurons were classified by their response to noise bursts in the ipsilateral or contralateral ears as ipsi units, contra units, or either-ear units. There were no significant differences in the distributions of these unit types between control and conditioned animals. There were also no differences in other responses to monaural stimuli, including the distribution of characteristic frequencies (CFs), the sharpness of tuning, or thresholds at the CF. For binaural sound at high levels, particularly relevant to sound-evoked activation of the MOC reflex during acoustic overstimulation, the firing rates of MOC neurons with CFs just above the conditioning band showed slight (but statistically significant) elevations relative to control animals. Frequency regions just above the conditioning band also demonstrated maximum conditioning-related protection; thus protection could be due, in part, to long-term changes in MOC discharge rates. For binaural sound at low levels, MOC firing rates in conditioned animals also were increased significantly relative to controls. Again, increases were largest for neurons with CFs just above the conditioning band. For equivalent monaural sound, rates were not significantly increased; thus, conditioning appears to increase binaural facilitation by opposite-ear sound. These data indicate that MOC neurons show long-term plasticity in acoustic responsiveness that is dependent on their acoustic history.     

Transmural potential changes associated with the in vitro absorption of theanine in the guinea pig intestine

Theanine, L-N-ethylglutamine, is one of the major components of amino acids in Japanese green tea. To characterize the mode for intestinal absorption of theanine, the ionic dependency and kinetic properties of the theanine- and glutamine-evoked transmural electrical potential difference changes (delta PD) were investigated in vitro by using everted sacs prepared from the guinea pig ileum. Both theanine and glutamine applied to the luminal side induced dose-dependent increases in delta PD (increase in serosal positive value). The theanine- and glutamine-evoked delta PD values conformed to the Michaelis-Menten relationship, with delta PDmax not being different, whereas the half-saturation concentration was lower for glutamine (3.1 +/- 0.2 mM) than for theanine (21.4 +/- 0.6 mM). The theanine-evoked delta PD value was much smaller when theanine was applied in the presence of glutamine than when applied alone. The theanine- and glutamine-evoked delta PD values were both inhibited by removing Na+ from the luminal solution. These results suggest that the intestinal absorption of theanine and glutamine is mediated by a common Na(+)-coupled co-transporter in the brush-border membrane, the affinity of which is lower for theanine than for glutamine.     

Single olivocochlear neurons in the guinea pig. I. Binaural facilitation of responses to high-level noise

Single medial olivocochlear (MOC) neurons were recorded from the cochlea of the anesthetized guinea pig. We used tones and noise presented monaurally and binaurally and measured responses for sounds up to 105 dB sound pressure level (SPL). For monaural sound, MOC neuron firing rates were usually higher for noise bursts than tone bursts, a situation not observed for afferent fibers of the auditory nerve that were sampled in the same preparations. MOC neurons also differed from afferent fibers in having less saturation of response. Some MOC neurons had responses that continued to increase even at high sound levels. Differences between MOC and afferent responses suggest that there is convergence in the pathway to olivocochlear neurons, possibly a combination of inputs that are at the characteristic frequency (CF) with others that are off the CF. Opposite-ear noise almost always facilitated the responses of MOC neurons to sounds in the main ear, the ear that best drives the unit. This binaural facilitation depends on several characteristics that pertain to the main ear: it is higher in neurons having a contralateral main ear (contra units), it is higher at main-ear sound levels that are moderate (approximately 65 dB SPL), and it is higher in neurons with low discharge rates to main-ear stimuli. Facilitation also depends on parameters of the opposite-ear sound: facilitation increases with noise level in the opposite ear until saturating, is greater for continuous noise than noise bursts, and is usually greater for noise than for tones. Using optimal opposite-ear facilitators and high-level stimuli, the firing rates of olivocochlear neurons range up to 140 spikes/s, whereas for moderate-level monaural stimuli the rates are <80 spikes/s. At high sound levels, firing rates of olivocochlear neurons increase with CF, an increase that may compensate for the known lower effectiveness of olivocochlear synapses on outer hair cells responding to high frequencies. Overall, our results demonstrate a high MOC response for binaural noise and suggest a prominent role for the MOC system in environments containing binaural noise of high level.     

The response of primary horizontal semicircular canal neurons in the rat and guinea pig to angular acceleration

In rats and guinea pigs, primary afferent neurons from the horizontal semicircular canal were divided into two categories, regular and irregular, on the basis of the regularity of their resting activity. Regular neurons tend to have higher average resting rates than irregular neurons and in response to a constant angular acceleration stimulus of 16.7 deg/s2 regular neurons tended to have lower sensitivity and longer time constants than irregular cells. Some irregular neurons are more sensitive to incremental accelerations than to decremental accelerations of the same magnitude, whereas regular neurons tend to show symmetrical sensitivity. In response to sinusoidal angular acceleration stimuli (fixed frequencies) in the range 0.01-1.5 Hz, cells which fired regularly at rest tended to have smaller gain and longer phase lag re acceleration at most frequencies than irregular cells. Transfer functions were obtained for averaged data for regular and irregular neurons separately in both species. In both species there is evidence of systematic variation between neurons within each category, and this systematic variation is obscured by averaging across neurons.