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Biomedical subjects

J C Bornstein

Publications and source records attributed to J C Bornstein.

At least 73 records · Page 4Linked to original sources
PubMed1993

Structure of the tertiary component of the myenteric plexus in the guinea-pig small intestine.

The tertiary component of the myenteric plexus consists of interlacing fine nerve fibre bundles that run between its principal ganglia and connecting nerve strands. It was revealed by zinc iodide-osmium impregnation and substance P immunohistochemistry at the light-microscope level. The plexus was situated against the inner face of the longitudinal muscle and was present along the length of the small intestine at a density that did not vary markedly from proximal to distal. Nerve bundles did not appear to be present in the longitudinal muscle as judged by light microscopy, although numerous fibre bundles were encountered within the circular muscle layer. At the ultrastructural level, nerve fibre bundles of the tertiary plexus were found in grooves formed by the innermost layer of longitudinal smooth muscle cells. In the distal parts of the small intestine, some of these nerve fibre bundles occasionally penetrated the longitudinal muscle coat. Vesiculated profiles in nerve fibre bundles of the tertiary plexus contained variable proportions of small clear and large granular vesicles; they often approached to within 50-200 nm of the longitudinal smooth muscle cells. Fibroblast-like cells lay between strands of the tertiary plexus and the circular muscle but were never intercalated between nerve fibre varicosities and the longitudinal muscle. These anatomical relationships are consistent with the tertiary plexus being the major site of neurotransmission to the longitudinal muscle of the guinea-pig small intestine.

Animals↗
PubMed1993

Simultaneous intracellular recordings from enteric neurons reveal that myenteric AH neurons transmit via slow excitatory postsynaptic potentials.

Simultaneous intracellular electrical recordings were made from pairs of neurons separated circumferentially by 100-200 microns of the myenteric plexus of the guinea-pig ileum in vitro. The recording electrodes were filled with the dye neurobiotin which was injected into impaled nerve cells, and later revealed histochemically. Intracellular current pulses were used to evoke action potentials via the recording electrode in one type of myenteric neuron, in most cases an AH neuron, while a second electrode was used to record from a simultaneously impaled S neuron or AH neuron. AH neurons are thought to be primary sensory neurons, whereas S neurons are interneurons and motor neurons. Ninety pairs of neurons were adequately tested for interaction. From these, 17 S neurons and three AH neurons that responded to AH neuron stimulation were detected. In each case, the response was a slow depolarization that was seen only in response to a train of stimuli at 10 Hz. The slow depolarizations were enhanced by passing depolarizing current and diminished by hyperpolarization. Responses were also diminished by lowering external Ca.2+ and elevating Mg2+. In all cases in which intracellular recording indicated communication between neurons, morphological evidence of connection was seen. In no case was there communication without connection, but in four instances, morphological connections appeared to exist, although no physiological evidence of communication was obtained.

Action Potentials↗
PubMed1992

Projections and chemical coding of neurons with immunoreactivity for nitric oxide synthase in the guinea-pig small intestine.

The distribution of nitric oxide synthase (NOS) immunoreactivity was investigated in the guinea-pig small intestine. There were many immunoreactive nerve cell bodies in the myenteric plexus but very few in submucous ganglia. NOS immunoreactivity was not found in non-neuronal cells except for rare mucosal endocrine cells. Abundant immunoreactive nerve fibres in both myenteric and submucous ganglia, and in the circular muscle, arose from myenteric nerve cells whose axons projected anally along the intestine. NOS immunoreactivity coexisted with VIP-immunoreactivity, but not with substance P immunoreactivity. We conclude that nitric oxide synthase is located in a sub-population of enteric neurons, amongst which are inhibitory motor neurons that supply the circular muscle layer.

Amino Acid Oxidoreductases↗
PubMed1992

Post-stimulus depression of reflex changes in circular muscle activity in the guinea pig small intestine.

The extent and time course of depression of successive reflex responses recorded with intracellular microelectrodes from the circular smooth muscle of the guinea pig small intestine were determined. Two stimuli were used, distension and distortion of the mucosa by compression; these were applied either at the same or at different sites. Excitatory responses oral and inhibitory responses anal to the stimuli were recorded. Post-stimulus depression of both ascending excitatory and descending inhibitory reflexes occurred, but the extent of depression was slightly less for the descending inhibition. A conditioning distension lasting 9 s depressed the excitatory response to a test distension applied 2 s later at the same site by 90%. After 30 s the depression was 50% and test responses were normal if inter-stimulus intervals were increased to 2 min. Increasing the duration of the conditioning stimulus increased the depression. Post-stimulus depression was less for compression stimuli than for distension stimuli and prior mucosal compression had almost no effect on responses to subsequent distension. The post-stimulus depression was greater if conditioning and test stimuli were at the same rather than different sites. For different sites, conditioning stimuli at 15 mm from the recording site (near) depressed responses to stimuli at 30 mm (far) to a greater extent than far stimuli depressed responses to near stimuli. If the conditioning stimulus at 15 mm was maintained until after the far test stimulus was applied, depression of the test response did not occur. It is concluded that the major sites of post-stimulus depression are at the synapses between primary sensory neurons and the first interneurons of reflex pathways, and that post-stimulus depression also occurs at other places in the pathway, presumably at synapses between interneurons or between interneurons and motor neurons.

Animals↗
PubMed1992

Roles of peptides in transmission in the enteric nervous system.

Studies of the enteric nervous system have proved to be important in the development of new concepts of the chemical nature of transmission from neurons. In particular, they have revealed the multiplicity of influences that peptides can have on transmission, such as their action as primary transmitters, and the fact that they often act as co-transmitters in enteric neurons. However, in other cases no roles can be attributed to neuropeptides in enteric neurons, and their involvement in short-term changes in excitability seems minor.

Animals↗
PubMed1992

Convergence of reflex pathways excited by distension and mechanical stimulation of the mucosa onto the same myenteric neurons of the guinea pig small intestine.

The effects on morphologically and electrophysiologically characterized myenteric neurons of activation of intestinal reflex pathways were examined in vitro. Opened segments of guinea pig small intestine were pinned serosa down in an organ bath that had two balloons set into its base. A 5-10-mm-wide strip of myenteric plexus between the balloons was exposed from the mucosal side, and neurons were impaled with microelectrodes. Reflex pathways were stimulated by inflation of the balloons to distend the intestinal wall, and by deforming the exposed mucosal villi with a brush. Impaled neurons were classified electrophysiologically as AH-neurons or S-neurons (Hirst et al., 1974) and were injected with biocytin to determine their shapes and projections. None of the 58 AH-neurons responded to distension. In contrast, 63 of 131 S-neurons responded to distension with a burst of fast EPSPs; about one-third of the responding S-neurons received input from ascending reflex pathways, one-third received input from descending reflex pathways, and one-third received input from both ascending and descending pathways. Most neurons in this last group supplied extensive varicose branches to the tertiary plexus and were probably longitudinal muscle motor neurons. Neurons receiving input from only one pathway usually projected in the direction of that pathway; many of these were circular muscle motor neurons. Almost all neurons responding to distension were also excited by deforming the villi. Responses evoked by distension or deforming the mucosa declined when stimuli were repeated at intervals less than 10 sec. This was seen in ascending and descending pathways but was more prominent in the former. Deforming the mucosa evoked a normal response even when the response to repeated distensions had disappeared. It is concluded that distension and deforming the mucosa excite separate populations of sensory neurons to activate reflex pathways that converge onto common motor neurons and probably onto common interneurons.

Animals↗
PubMed1991

Ramifications of the axons of AH-neurons injected with the intracellular marker biocytin in the myenteric plexus of the guinea pig small intestine.

The projections and terminal ramifications of electrophysiologically characterized myenteric neurons of the guinea pig small intestine were studied after intracellular injection of the marker substance biocytin. Myenteric neurons were impaled with microelectrodes containing 4% biocytin in 2 M KCl (pH 7.4) and characterized electrophysiologically as either AH-neurons or S-neurons. AH-neurons were neurons in which action potentials were followed by prolonged after-hyperpolarizations (lasting greater than 4 seconds). S-neurons were neurons in which such hyperpolarizations were not seen. Electrical stimulation of internodal strands evoked prominent fast excitatory synaptic potentials in S-neurons, but not in AH-neurons. Biocytin was injected electrophoretically into the impaled AH-neurons by passage of hyperpolarizing current (0.6-0.8 nA for 5-15 minutes) through the recording electrode. The preparation was then fixed in Zamboni's fixative, dehydrated, and exposed to avidin coupled to horseradish peroxidase which allowed the injected biocytin to be visualised via a diaminobenzidine reaction. In many cases, the injected biocytin appeared to fill all the processes of injected AH-neurons that ramified within the myenteric plexus. The filled processes included axons running up to 4 mm within the plexus and profuse varicose terminals ramifying within both the ganglion containing the injected cell body and nearby ganglia. Most (90%) cell bodies of the injected AH-neurons had the morphology of Dogiel type II neurons; large, mostly smooth cell bodies with few short processes and several long processes. The other 10% of the AH-neurons had similar cell bodies and long processes but also had prominent short filamentous processes. This population was termed dendritic AH-neurons. The projections and terminals of 28 AH/Dogiel type II neurons and 7 dendritic AH-neurons were analysed in detail. Both types of neurons project circumferentially to provide terminals to nearby ganglia, but the AH/Dogiel type II neurons also provide terminals to their own ganglia while the dendritic AH-neurons typically do not. Although many of the injected AH-neurons had projections orally or anally along the intestine no evidence for a preferential direction of projection was obtained. Analysis of the areas and distributions of the terminal fields of the AH/Dogiel type II neurons suggests that each may contact several other myenteric neurons and that each myenteric neuron may receive input from about ten AH/Dogiel type II neurons.

Action Potentials↗
PubMed1991

Interactions between reflexes evoked by distension and mucosal stimulation: electrophysiological studies of guinea-pig ileum.

Intracellular recording methods were used to examine stereotyped reflexes evoked in the circular muscle of guinea-pig small intestine by distension or repetitive deformation of the mucosal villi, in vitro. Both stimuli evoked compound excitatory junction potentials (EJPs) on the oral side of the site of stimulation and compound inhibitory junction potentials (IJPs) on the anal side. Stimulation of the mucosa by application of 10 microliters of 0.5 M HCl evoked similar reflex responses in the circular muscle. The compound EJPs evoked by mucosal stimulation were depressed, but not abolished, by 1 microM hyoscine, indicating that these responses were partially mediated by release of acetylcholine, as are the equivalent responses evoked by distension. The compound EJPs and the compound IJPs evoked by maintained distension or by repeated mechanical stimulation of the mucosa were transient, lasting in most cases for 3-5 s before the membrane potential returned to resting level. This decline (rundown) occurred in part of the circuit close to the site of stimulation as stimuli applied elsewhere during the period of rundown evoked normal EJPs and IJPs. Mechanical stimuli (brush strokes that deformed the mucosal villi) applied to the mucosa at the site of a maintained distension evoked responses of normal amplitude during the period when the response to the distension had declined to zero. In contrast, during the period when the responses to repetitive mechanical stimulation of the mucosa had disappeared, the reflex responses evoked by distension at the same site were substantially augmented. Chemical stimulation of the mucosa with acid also enhanced the responses to distension.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1991

Mucosal distortion by compression elicits polarized reflexes and enhances responses of the circular muscle to distension in the small intestine.

The possibility that distortion of the mucosa by compression might be a sufficient stimulus to evoke reflex responses in intestinal muscle, and that such reflexes might summate with distension-evoked (stretch) reflexes, was tested in isolated segments of guinea pig small intestine. Opened segments of intestine were pinned flat in an organ bath with, or without, distending balloons embedded in its base. Intracellular microelectrode recordings were taken from the circular muscle oral and anal to sites of application of sensory stimuli. Pressure against the mucosa, which distorts the villi without the wall being stretched, evoked polarized reflex responses in the circular muscle, consisting of excitatory junction potentials oral and inhibitory junction potentials anal to the stimulus. Distension stimuli applied by 6-mm diameter balloons that pushed against either the serosal or the mucosal surface also evoked excitatory junction potentials in the muscle oral to the stimulus and inhibitory junction potentials at anal sites. Response amplitudes were 20% greater when the distending balloon pushed against the mucosal surface. Responses to distension from the serosal side were of 20% greater amplitude when combined with mucosal distortion by compression than without such compression. It is concluded that peristaltic movements that are commonly studied in the small intestine can be consequences of reflexes elicited at the same time from mucosal distortion receptors and from stretch receptors.

Animals↗
PubMed1991

Synaptic responses evoked by mechanical stimulation of the mucosa in morphologically characterized myenteric neurons of the guinea-pig ileum.

Recordings were made from myenteric neurons of the guinea-pig ileum during reflexes evoked by mechanical stimulation of the mucosa. Impaled neurons were injected with dye (Lucifer yellow or biocytin), and their shapes were determined. All neurons were 5-12 mm from the stimulus, a brush stroke that deformed the mucosal villi. Neurons were classified as S-neurons or AH-neurons (Hirst et al., 1974). About 40% of S-neurons oral to a stimulus responded with bursts of fast EPSPs (average frequency, 15-40 Hz); these neurons were in ascending reflex pathways. About 60% of S-neurons anal to a stimulus responded with similar bursts of fast EPSPs or slow depolarizations; these neurons were in descending pathways. Only 2 of 48 AH-neurons responded, both in descending pathways. Most S-neurons in either ascending or descending pathways received inputs from at least 2 or 3 other neurons. Action potentials evoked during a response averaged 3-10 Hz in frequency, with occasional bursts at up to 100 Hz. The speed of conduction along the reflex pathways was about 0.5 m/sec. All S-neurons were uniaxonal, but they differed in size, dendritic morphology, and projections. The axons of S-neurons injected with biocytin were followed up to 7 mm within the myenteric plexus. Three S-neurons projected to the tertiary plexus and were probably longitudinal muscle motor neurons; 2 of these were in descending pathways. Five S-neurons projected along the intestine and had varicose collaterals in some ganglia. These neurons were probably interneurons; 3 were descending and 2 ascending, and all responded in the appropriate reflex pathway. Many S-neurons had short axons that entered the circular muscle and were probably circular muscle motor neurons. Others projected several millimeters along the intestine before entering the circular muscle or fading beyond detection. From this study, we have been able to deduce the circuits mediating ascending and descending mucosa-to-muscle reflexes. It is concluded that AH-neurons are primary sensory neurons and S-neurons are interneurons and muscle motor neurons in the circuits.

Animals↗
PubMed1990

An electrophysiological study of the projections of putative sensory neurons within the myenteric plexus of the guinea pig ileum.

Conduction of action potentials in the processes of AH (afterhyperpolarizing) neurons has been examined in the myenteric plexus of the guinea-pig small intestine. AH neurons are a morphologically distinct class of myenteric neurons in which the action potentials are followed by long lasting afterhyperpolarizations and which usually lack fast synaptic inputs. These neurons have large smooth cell bodies and several long processes. We have used electrophysiological methods, combined with intracellular injection of the fluorescent dye 5(6)-carboxyfluorescein, to examine the directions of projection and lengths of axons of AH neurons. AH neurons of the myenteric plexus projected circumferentially in both directions from the cell soma for electrophysiologically determined average distances of 0.74 +/- 0.05 mm. Thus, the neurons span about 1.5 mm of the circumference of the intestine. About one quarter of the AH neurons had one, or rarely two, processes that ran anally after initially projecting circumferentially. All processes conducted action potentials, with average conduction velocities of 0.23 +/- 0.02 ms-1.

Action Potentials↗
PubMed1990

Calbindin neurons of the guinea-pig small intestine: quantitative analysis of their numbers and projections.

The distribution of nerve cells with immunoreactivity for the calcium-binding protein, calbindin, has been studied in the small intestine of the guinea-pig, and the projections of these neurons have been analysed by tracing their processes and by examining the consequences of nerve lesions. The immunoreactive neurons were numerous in the myenteric ganglia; there were 3500 +/- 100 reactive nerve cells per cm2 of undistended intestine, which is 30% of all nerve cells. In contrast, reactive nerve cells were extremely rare in submucous ganglia. The myenteric nerve cells were oval in outline and gave rise to several long processes; this morphology corresponds to Dogiel's type-II classification. Processes from the cell bodies were traced through the circular muscle in perforating nerve fibre bundles. Other processes ran circumferentially in the myenteric plexus. Removal of the myenteric plexus, allowing time for subsequent fibre degeneration, showed that reactive nerve fibres in the submucous ganglia and mucosa came from the myenteric cell bodies. Operations to sever longitudinal or circumferential pathways in the myenteric plexus indicated that most reactive nerve terminals in myenteric ganglia arise from myenteric cell bodies whose processes run circumferentially for 1.5 mm, on average. It is deduced that the calbindin-reactive neurons are multipolar sensory neurons, with the sensitive processes in the mucosa and with other processes innervating neurons of the myenteric plexus.

Animals↗
PubMed1990

Distension-evoked ascending and descending reflexes in the circular muscle of guinea-pig ileum: an intracellular study.

Reflex responses evoked by distension of the guinea-pig small intestine were recorded from the circular muscle with intracellular microelectrodes. For this purpose a mechanically stable preparation that allowed the intestinal wall to be distended within 9 mm of the recording site was developed. A segment of intestine was opened along the mesenteric border and pinned mucosa uppermost over a balloon set in the base of an organ bath, so that inflation of the balloon could distend the intestinal wall without simultaneously pushing against the mucosa. Compound excitatory junction potentials (EJPs) and compound inhibitory junction potentials (IJPs) were recorded at sites up to 40 mm oral and anal to the distending stimulus, respectively. The compound EJPs recorded orally had amplitudes of up to 24 mV and declined to baseline during distensions that exceeded 10-15 s. Distensions at intervals of less than 20 s evoked successively smaller oral compound EJPs; after four distensions in 30 the amplitude of the compound EJP had fallen to less than 10%. The amplitude of the oral compound EJP was reduced by hyoscine (1 microM), but the extent of the reduction depended on the degree of distension; responses to mild stimuli were blocked, whereas those to strong stimuli were only slightly reduced. The amplitude of the hyoscine-resistant component of the compound EJP was markedly reduced by antagonists of substance P receptors in the muscle. In the presence of muscarinic and substance P receptor antagonists, a transient compound IJP could be detected on the oral side of the stimulus. The compound IJPs recorded anal to the distension had amplitudes up to 22 mV but the potential returned to baseline during prolonged distension. In the presence of hyoscine (1 microM) some inhibitory activity continued throughout prolonged stimuli. Compound IJP amplitudes were not significantly reduced by repeated distensions separated by more than 6 s. At anal sites a transient depolarization (off-response) was recorded immediately following the termination of a distension in some preparations. The off-response was unaffected by hyoscine and was more readily observed after the further addition of substance P antagonists. The compound IJPs were almost completely blocked by apamin (0.2 microM). The compound EJPs and IJPs recorded orally were blocked by hexamethonium (100 microM), but the amplitudes of compound IJPs recorded anally were significantly reduced by hexamethonium (100-200 microM) only at recording sites greater than 15 mm from the centre of the balloon. The off-response was reduced by hexamethonium at all sites.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMed1989

Shapes and projections of neurons with immunoreactivity for gamma-aminobutyric acid in the guinea-pig small intestine.

The distribution of nerve cell bodies and fibres with immunoreactivity for gamma-aminobutyric acid (GABA) has been studied in the guinea-pig small intestine. Cell bodies were common in myenteric ganglia but were extremely rare in the submucosa. Reactive fibres were numerous in the tertiary component of the myenteric plexus and in the circular muscle but they were rare in both myenteric and submucous ganglia. Reactive nerve fibres were absent from the mucosa. This distribution conforms to previous descriptions. Exposure to exogenous GABA, in vitro, was used to supplement endogenous stores of GABA. The morphology of cell bodies was better defined after this treatment. Nearly all cell bodies had type-I morphology, i.e., the cells had numerous short lamellar dendrites and one axon. Most axons ran anally. Some could be traced to the tertiary component of the myenteric plexus, others to the circular muscle. Removal of the myenteric plexus from a short length of intestine caused a loss of nerve fibres from the circular muscle beneath the site of operation and a decrease in fibre density in the circular muscle that extended anally from the lesion for about 1 mm. The nerve lesions caused no significant changes in the tertiary plexus. It is concluded that GABA is contained in motor neurons supplying the longitudinal and circular muscle, and that the neurons supplying the circular muscle may be inhibitory.

Animals↗
PubMed1989

Evidence for two types of 5-hydroxytryptamine receptor on secretomotor neurons of the guinea-pig ileum.

Flat sheet preparations of the mucosa plus submucosa from the guinea-pig ileum were placed in Ussing chambers so that short circuit current (Isc), an index of electrolyte movement across the mucosa, could be measured. In these preparations, 5-hydroxytryptamine (5-HT) increases Isc indirectly by stimulating both cholinergic and non-cholinergic secretomotor neurons. The 5-HT3 receptor antagonist, ICS 205-930 (10(-13)-10(-5 M), substantially depressed the secretory response due to 5-HT (10(-6) M), but not that produced by direct activation of muscarinic receptors on the mucosal epithelium with carbachol (10(-6) M), or by stimulation of secretomotor neurons with substance P (10(-8) M) or 1,1-dimethyl-4-phenylpiperazinium (10(-5)M). The residual response to 5-HT, after the addition of a maximally effective concentration of ICS 205-930 (10(-6) M), was further reduced by hyoscine (10(-7) M). When that part of the 5-HT response attributable to the release of acetylcholine was blocked by hyoscine (10(-7) M), ICS 205-930 did not further modify the response to 5-HT. The hyoscine-resistant component was, however, substantially depressed by tetrodotoxin (3.5 x 10(-7) M). The response remaining after ICS 205-930 and hyoscine was not affected by methysergide (2 x 10(-5) M) or cyproheptadine (10(-7) M). We conclude that there are ICS 205-930 sensitive 5-HT receptors on cholinergic secretomotor neurons, and ICS 205-930, methysergide, and cyproheptadine insensitive 5-HT receptors on non-cholinergic secretomotor neurons.

Animals↗
PubMed1989

An electrophysiological comparison of substance P-immunoreactive neurons with other neurons in the guinea-pig submucous plexus.

Intracellular microelectrodes containing the dye Lucifer yellow CH were used to record from nerve cells of ganglia in isolated preparations of submucosa from the guinea-pig small intestine. The electrophysiological properties of the neurons were investigated by passing intracellular current pulses and by stimulating nerve strands that connect with the ganglia. Following each electrophysiological investigation, the fluorescent dye was injected into the neuron by passing hyperpolarizing currents through the electrode. The preparations were fixed and processed for substance P (SP) immunohistochemistry. When impaled neurons were not immunoreactive for SP the preparations were processed first for vasoactive intestinal peptide immunoreactivity and then for neuropeptide Y immunoreactivity. Data from neurons reactive for either of these peptides were pooled for comparison with the data from SP-immunoreactive neurons. Nerve cells that were immunoreactive for SP were usually multipolar, had broad action potentials (half width 2.6 ms compared with 1.5 ms for other submucous neurons) and lower input resistances than other submucous neurons. Only a minority (6 of 18) had demonstrable fast excitatory synaptic inputs. When such excitatory synaptic inputs were observed, these did not initiate action potentials. Thus, the SP-immunoreactive neurons were readily distinguishable from other submucous neurons. It is concluded that these neurons are likely to be sensory.

Animals↗