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J C Bornstein

Publications and source records attributed to J C Bornstein.

At least 91 records · Page 5Linked to original sources
PubMed1989

Correlated functional and structural analysis of enteric neural circuits.

Views about the roles and nature of the enteric nervous system have changed dramatically in the last ten years. This system of neurons is recognized to control, through reflex pathways intrinsic to the gut wall, motility, transport of water and electrolytes, and blood flow in the small and large intestines. There are thus a range of neuron types in the enteric nervous system, including sensory neurons, motor neurons, and interneurons, involved in the control of each of these functions. The present paper deals with the recent efforts to provide an integrated functional and structural description of the nerve circuits. One of the challenges in this quest has been to identify primary sensory neurons and final motor neurons involved in motility control. Evidence is presented that in the guinea-pig small intestine the primary sensory neurons have Dogiel type II morphology and are, electrophysiologically, AH neurons. They send circumferential processes to adjacent myenteric ganglia and some of them, at least, have processes leading from the mucosa. Motor neurons are S neurons, with cell bodies in the myenteric plexus. Those that supply the circular muscle are Dogiel type I neurons and provide processes that run circumferentially for about one third of the circumference of the intestine. The circuits for secretomotor reflexes have been partly worked out. The secretomotor neurons have cell bodies in the submucous ganglia and are activated to return water and electrolytes to the lumen during digestion. The secretomotor reflexes are regulated, in accord with whole body water and electrolyte homeostasis, via sympathetic neurons which lower the excitability of secretomotor neurons.

Animals↗
PubMed1988

Localization of substance P binding sites in submucous plexus of guinea pig ileum, using whole-mount autoradiography.

Whole mounts of guinea pig ileum submucosa were incubated with radiolabeled tachykinins, and binding sites were visualized using autoradiography. Very dense specific binding for [125I]-Bolton-Hunter substance P (BHSP) was observed over ganglia of the submucous plexus, with weaker binding over internodal strands. Dense specific binding was also seen over occasional strands of circular muscle, with weak binding over clumps of mucosa. Although very weak binding was seen over some large blood vessels, no binding was associated with smaller blood vessels. Localization of binding was absent in whole-mounts coincubated with 1 microM substance P, used to define nonspecific binding. Localization of BHSP-specific binding was also abolished in whole-mounts coincubated with 1 nM substance P, but not with 1 nM neurokinin B, suggesting that binding was probably to an NK-1 tachykinin receptor. In whole-mounts incubated in [125I]-iodohistidyl neurokinin A (INKA) or [125I]-Bolton-Hunter neurokinin B (BHNKB), no specific binding over ganglia was observed. These binding sites for BHSP are probably identical with the neuronal substance P receptors mediating mucosal ion transport.

Animals↗
PubMed1988

Immunohistochemical evidence for the presence of calcium-binding proteins in enteric neurons.

Immunoreactivity for vitamin D-dependent calcium-binding protein (CaBP) has been localized in nerve cell bodies and nerve fibres in the gastrointestinal tracts of guinea-pig, rat and man. CaBP immunoreactivity was found in a high proportion of nerve cell bodies of the myenteric plexus, particularly in the small intestine. It was also found in submucous neurons of the small and large intestines. Immunoreactive nerve fibres were numerous in the myenteric ganglia, and were also common in the submucous ganglia and in the intestinal mucosa. Immunoreactive fibres were rare in the circular and longitudinal muscle coats. In the myenteric ganglia of the guinea-pig small intestine the immunoreactivity is restricted to one class of nerve cell bodies, type-II neurons of Dogiel, which display calcium action potentials in their cell bodies. These neurons were also immunoreactive with antibodies to spot 35 protein, a calcium-binding protein from the cerebellum. From the distribution of their terminals and the electrophysiological properties of these neurons it is suggested they might be sensory neurons, or perhaps interneurons. The discovery of CaBP in restricted sub-groups of enteric neurons may provide an important key for the analysis of their functions.

Animals↗
PubMed1988

Shapes of nerve cells in the myenteric plexus of the guinea-pig small intestine revealed by the intracellular injection of dye.

The shapes of myenteric neurons in the guinea-pig small intestine were determined after injecting living neurons with the dye Lucifer yellow via a microelectrode. The cells were fixed and the distribution of Lucifer yellow rendered permanent by an immunohistochemical method. Each of 204 nerve cells was examined in whole-mount preparations of the myenteric plexus and drawn using a camera lucida at 1250 x magnification. Four cell shapes were distinguished: (1) neurons with several long processes corresponding to type II of Dogiel; (2) neurons with a single long process and lamellar dendrites corresponding to type I of Dogiel; (3) neurons with numerous filamentous dendrites; and (4) small neurons with few processes. About 15% of the neurons could not be placed into these classes or into any single class. The type II neurons (39% of the sample) had generally smooth somata and up to 7 (average 3.3) long processes, most of which ran circumferentially. Dogiel type I neurons (34% of sampled neurons) had characteristic lamellar dendrites, i.e., broad dendrites that were flattened in the plane of the plexus. The filamentous neurons (7% of the sample), had, on average, 14 fine processes up to about 50 microns in length. Small neurons with smooth outlines and a few fine processes made up 5% of the neurons encountered. We conclude that myenteric neurons that have been injected with dye can be separated into morphologically distinct classes and that the different morphological classes probably correspond to different functional groupings of neurons.

Animals↗
PubMed1988

Correlated electrophysiological and histochemical studies of submucous neurons and their contribution to understanding enteric neural circuits.

Neither submucous ganglia, nor intestinal secretomotor reflexes are mentioned in the majority of the textbooks of physiology; because it has been realized only very recently that the submucous neurons may have important influences on whole body water and electrolyte balance. In the present review, we trace the rapid progress that has been made in determining the physiological properties of submucous neurons with known chemistry and projections in the guinea-pig small intestine, and we analyze how the work relates to studies in vivo of the neuronal control of intestinal trans-epithelial fluid transport. Four types of submucous neurons, which appear to be the full complement in the guinea-pig small intestine, have been identified through electrophysiological and histochemical analysis. (1) Cholinergic secretomotor neurons contain immunoreactivity for choline-acetyltransferase (ChAT), calcitonin gene-related peptide (CGRP), cholecystokinin (CCK), neuropeptide Y (NPY), somatostatin (SOM), and in the majority of cases galanin (GAL); these neurons project to the mucosal epithelium. (2) Non-cholinergic secretomotor neurons contain dynorphin (DYN), GAL and vasoactive intestinal peptide (VIP); these neurons project to the mucosa and provide collaterals to submucous arterioles. (3) Cholinergic interneurons contain ChAT alone; these neurons connect with the secretomotor neurons. (4) Presumed sensory neurons contain ChAT and substance P (SP) and have nerve endings in the mucosa. The two groups of secretomotor neurons receive cholinergic synaptic inputs from both myenteric and submucous ganglia. In addition, the DYN/GAL/VIP neurons receive sympathetic inhibitory inputs as well as inhibitory and non-cholinergic excitatory inputs from myenteric ganglia. The ChAT/SP nerve cells in submucous ganglia receive no or very ineffective inputs. From these data, from experiments on transmission from the neurons to the intestinal epithelium, and from studies of secretomotor reflexes in vivo, a correlated functional and structural circuitry of the submucous ganglia and their connections has been deduced. It is concluded that secretomotor reflexes are stimulated by the contents of the lumen during the digestion and absorption of food and that these reflexes cause a proportion of water and electrolytes that are absorbed with nutrients such as glucose to be returned to the lumen. The balance of absorption and secretion of water and electrolytes is controlled by sympathetic inhibitory inputs to secretomotor neurons, the activity in sympathetic pathways being varied to contribute to whole body water and electrolyte balance.

Action Potentials↗
PubMed1988

An electrophysiological study of the projections of motor neurones that mediate non-cholinergic excitation in the circular muscle of the guinea-pig small intestine.

The projections of neurones that produce the fast non-cholinergic excitatory junction potentials (e.j.p.s) in the circular muscle were analysed in the isolated ileum of the guinea-pig. Standard intracellular microelectrode techniques were used to record the amplitudes of such e.j.p.s in response to short trains of stimuli from transmural electrodes. Projections of the neurones around the circumference of the intestine were determined by plotting the change in e.j.p. amplitude with distance from longitudinally placed electrodes. Projections in the oral and anal directions were examined by recording at varying distances from transversely placed electrodes, and also by recording responses elicited close to longitudinal electrodes at various distances from lesions made 3-5 days earlier to interrupt orally and anally directed pathways. Experiments were performed in the presence of hexamethonium to determine the projections of the final motor neurones and in the absence of the drug to examine the projections of excitatory inputs to these neurones. With hexamethonium present, there was a decline in e.j.p. amplitude to 7.5% of maximum at 12 mm (a half circumference) from longitudinal stimulating electrodes. The decline was much less if hexamethonium was not present, and slightly greater if the myenteric plexus was removed. Thus, excitatory motor neurones and cholinergic neurones that impinge upon them both project circumferentially. When the longitudinal muscle and myenteric plexus were removed, and 3-5 days allowed for terminals to degenerate, no e.j.p.s could be recorded in the circular muscle, indicating that the fibres reach the circular muscle from the myenteric plexus. Following transverse lesions, substantial deficits in excitatory transmission only occurred within 1 mm oral or anal to the lesions indicating that the majority of neurones have only short projections along the intestine. A slight deficit in e.j.p. amplitude, up to 20%, was observed extending to about 5 mm oral; but normal transmission was restored by about 10 mm for the lesions. Thus there is a minority of excitatory motor neurones with oral projections up to about 10 mm in length. Results with transmural stimulation showed that these nerve fibres can cause excitation both when orthodromically and when antidromically stimulated, indicating that they provide collaterals along their lengths. With no hexamethonium present, e.j.p.s exhibited little decrement in amplitude over distances of over 30 mm oral or anal indicating that there are both ascending and descending cholinergic pathways that impinge on the final motor neurones.(ABSTRACT TRUNCATED AT 400 WORDS)

Action Potentials↗
PubMed1988

Electrophysiology of guinea-pig myenteric neurons correlated with immunoreactivity for calcium binding proteins.

Experiments were undertaken to define the electrophysiological characteristics and shapes of neurons in the myenteric plexus of the guinea-pig ileum that are immunoreactive for calcium binding proteins. Recordings were made from the neurons with intracellular microelectrodes containing a mixture of the fluorescent dye Lucifer yellow and KCl solution. The neurons studied were filled with Lucifer yellow so that they could be re-identified after processing the tissue to reveal immunoreactivity for either the calcium binding protein (CaBP), spot 35 protein, or vitamin D-dependent CaBP. Neurons were characterized as being AH-neurons, in which each action potential is followed by a prolonged after-hyperpolarization (greater than 4 s), or S-neurons, in which the prolonged after-hyperpolarizations were not observed and focal stimulation of internodal strands evoked fast excitatory synaptic potentials. S-neurons were never immunoreactive for the CaBPs (108 cells), but most AH-neurons (62 of 74) were immunoreactive. Immunoreactive and non-immunoreactive AH-neurons were indistinguishable on the basis of their electrophysiological properties or their shapes (all the AH-neurons were Dogiel type II in shape, i.e. smooth soma and many long processes). The S-neurons had a variety of shapes, but none could be classified as Dogiel type II. It is concluded that most AH-neurons are immunoreactive for calcium binding proteins, and that these proteins are restricted to AH-neurons.

Animals↗
PubMed1988

Intrinsic and extrinsic inhibitory synaptic inputs to submucous neurones of the guinea-pig small intestine.

1. The sources of inhibitory synaptic inputs to neurones in submucous ganglia of the guinea-pig small intestine were examined by making lesions to cause selective degeneration of nerve terminals of sympathetic or intrinsic origin. Intracellular recordings were used to evaluate the effects of lesions on the inhibitory inputs. Immunohistochemical techniques were used to identify the neurochemical classes of the impaled neurones and to confirm the efficacy of the lesions. 2. The neurones from which recordings were taken were filled with the fluorescent dye Lucifer Yellow. The preparations were then fixed and processed for immunohistochemistry. 3. Thirty-one neurones reactive for vasoactive intestinal polypeptide (VIP) were examined in control submucous ganglia and all exhibited inhibitory synaptic potentials. In preparations extrinsically denervated by severing the mesenteric nerves, twenty-seven of twenty-eight VIP-reactive neurones had inhibitory synaptic potentials. This indicates that these neurones receive inhibitory synaptic inputs from intrinsic neurones. However, significantly more stimuli were required to evoke a detectable inhibitory synaptic potential in extrinsically denervated preparations than in normal intestine. 4. Extrinsic denervations were combined with removal of the myenteric plexus so that nerve terminals arising from both cell bodies in extrinsic ganglia and in the myenteric plexus degenerated. Under these conditions no inhibitory synaptic potentials could be recorded in any of the nine VIP-reactive neurones studied. 5. The conductance change underlying the intrinsic inhibitory synaptic potentials appeared to be similar to that underlying the responses in normal intestine. 6. The time courses of the intrinsic inhibitory synaptic potentials differed from those of the control responses. The responses to short trains of stimuli were significantly briefer and the responses to long trains significantly more prolonged in the extrinsically denervated preparations than in normal preparations. 7. The intrinsic inhibitory synaptic potentials were not significantly affected by phentolamine (0.2 microM), guanethidine (1 microM) or naloxone (1 microM), although the first two drugs markedly depressed control inhibitory synaptic potentials.(ABSTRACT TRUNCATED AT 400 WORDS)

Action Potentials↗
PubMed1987

Sources of excitatory synaptic inputs to neurochemically identified submucous neurons of guinea-pig small intestine.

The locations of the cell bodies of axons responsible for synaptic potentials evoked in neurochemically identified submucous neurons of the guinea-pig small intestine were investigated using a combination of intracellular recording, immunohistochemical and lesioning techniques. The myenteric plexus was removed from an 8-15 mm wide ring of small intestine in 15 anaesthetized guinea-pigs. After the operations, the animals were allowed to recover for 3-7 days so that nerve terminals that were disconnected from their cell bodies would degenerate. Preparations of submucous plexus were then made from the region under the lesion. Submucous neurons were impaled with electrodes containing a mixture of KCl and the fluorescent dye, Lucifer yellow CH, and their electrophysiological properties determined. They were then filled with the dye for subsequent reidentification after processing for immunohistochemical localization of vasoactive intestinal peptide (VIP) and neuropeptide Y (NPY). The synaptic inputs to 33 neurons were characterized: 19 of these were found to be VIP-reactive, 7 were NPY-reactive and 7 were negative for both VIP and NPY. These results were compared to those obtained from 43 neurons in control preparations: 25 VIP-reactive, 9 NPY-reactive and 9 negative for both VIP and NPY. Removal of the myenteric plexus caused a significant reduction in the number of inputs providing fast excitatory synaptic potentials to each of the neurochemically defined classes of neurons. The lesions also caused a significant reduction in the number of VIP-reactive neurons that exhibited slow excitatory synaptic potentials (other neurochemical types do not normally exhibit such responses).(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1986

Electrophysiological analysis of projections of enteric inhibitory motoneurones in the guinea-pig small intestine.

The projections of neurones that produce inhibitory junction potentials (i.j.p.s) have been analysed in the small intestine of the guinea-pig. Intracellular microelectrodes were used to record i.j.p.s in circular muscle cells in response to stimulation with pairs of electrodes placed parallel to or across the length of the intestine (longitudinal and transverse electrodes, respectively). In preparations of circular muscle with the myenteric plexus attached, the mean amplitude of i.j.p.s recorded 9 mm lateral to longitudinal electrodes was about 70% of that seen at 1 mm; however, in the presence of hexamethonium (400 microM) the amplitude fell more rapidly to about 40% at 9 mm. The decline was even steeper in preparations of circular muscle from which the myenteric plexus had been removed, with the amplitude falling to 10% at 9 mm. I.j.p.s were detected up to 30 mm anal to stimuli applied with transverse electrodes in the presence of hexamethonium, but the decline was more rapid on the oral side, with i.j.p.s being detected only up to 12 mm oral to the stimulus. Nerves that travel through or originate in the myenteric plexus were severed or removed in operations performed 2-7 days before tissue was taken. 2-3 days after removal of a circumferential strip of myenteric plexus, i.j.p.s could not be recorded from the underlying circular muscle. I.j.p.s evoked by longitudinal electrodes were recorded in an area between two circumferential cuts through the myenteric plexus, 1.5-8 mm apart, 3-7 days after an operation. In this region, the i.j.p.s were significantly smaller than normal although amplitudes of up to 95% of control were measured. The consequences of single circumferential cuts through the myenteric plexus were examined 3 and 7 days after operation. Longitudinal electrodes were used to stimulate surviving fibres. Small i.j.p.s were recorded on the anal edge of the lesion; the amplitude recovered to 56% of normal in the first 2 mm on the anal side and the amplitude slowly returned to normal at 20 mm anal. On the oral side there was slight reduction in amplitude at 0.5 and 1 mm, but at greater distances amplitudes were normal. It is concluded that the simplest explanation of these results is that two populations of i.j.p.-producing neurones have their cell bodies in the myenteric plexus. Many axons supply the circular muscle close to or just anal to their cell bodies, and others run for various distances up to 30 mm in the anal direction.(ABSTRACT TRUNCATED AT 400 WORDS)

Action Potentials↗
PubMed1986

Synaptic inputs to immunohistochemically identified neurones in the submucous plexus of the guinea-pig small intestine.

1. Electrophysiological recordings were made from neurones in the submucous plexus of the guinea-pig small intestine, and these neurones were classified according to their synaptic inputs. 2. The neurones from which recording were made were filled during the recording period with the fluorescent dye, Lucifer Yellow, so they could be re-identified after processing for immunohistochemical localization of vasoactive intestinal peptide (VIP). 3. The presence or absence of VIP-like immunoreactivity was determined for a total of 130 neurones whose synaptic inputs had been fully characterized and eighty-two were found to be VIP reactive. After the VIP reactivity had been assessed, the preparations were reprocessed to reveal immunoreactivity for neuropeptide Y (NPY) and a further twenty-three neurones (none of which were reactive for VIP) were found to be reactive for this peptide. Of the remaining twenty-five neurones, nineteen were not reactive for either VIP or NPY and six could not be re-identified after reprocessing. 4. Electrical stimulation of internodal strands evoked excitatory synaptic potentials lasting 20-30 ms (fast responses) in all but one of the 130 neurones studied. 5. Almost all the VIP-reactive neurones (seventy-eight of eighty-two cells) exhibited inhibitory synaptic potentials, ranging in amplitude from 2 to 30 mV and lasting 150-1500 ms, but few of the VIP-negative neurones had such responses (six of forty-eight cells). No inhibitory synaptic potentials could be evoked in any of the NPY-reactive neurones. 6. Most VIP-reactive neurones (sixty-nine) had a slow excitatory synaptic potential which could be evoked by a single stimulus, lasted 5-20 s and was associated with an increase in input resistance. Only one NPY-reactive neurone had a slow excitatory potential, but such potentials were seen in nine of the nineteen VIP-negative, NPY-negative neurones. 7. In nine of the twenty-three NPY-reactive neurones a single stimulus evoked an excitatory synaptic potential (intermediate excitatory synaptic potential) lasting 500-1500 ms and associated with a fall in the input resistance. None of the VIP-negative, NPY-negative neurones exhibited the intermediate excitatory potentials but it was not possible to determine whether such potentials could be evoked in VIP-reactive neurones because the inhibitory synaptic potentials would obscure such events. 8. It is concluded that neurochemically distinct populations of submucous neurones can be distinguished physiologically on the basis of the differing combinations of types of synaptic input they receive.

Action Potentials↗
PubMed1984

Excitatory synaptic potentials due to activation of neurons with short projections in the myenteric plexus.

Intracellular microelectrodes have been used to examine the effects, on excitatory inputs to myenteric nerve cells, of lesions of intrinsic pathways in the myenteric plexus of the guinea-pig small intestine. The lesions consisted of circumferential cuts (myotomies) which severed the external musculature to the depth of the submucosa and thus interrupted pathways in the myenteric plexus. Sufficient time was allowed between creating the lesions and recording from the neurons for the endings of severed neurites to degenerate and this was confirmed histochemically by examining the distribution of varicose fibres with 5-hydroxytryptamine immunoreactivity in myenteric ganglia from which recordings were made. Two types of excitatory input, eliciting fast and slow excitatory post-synaptic potentials, respectively, were demonstrable in response to focal stimulation of nerves in the ganglia from which recordings were made. There were no differences in the proportions of neurons in which fast or slow excitatory synaptic potentials were evoked in unoperated preparations (controls), in islands 1.5-4 mm wide between myotomies, or within 1 mm on the oral or anal sides of myotomies. Possible differences in the amplitudes, durations at half amplitude, and threshold numbers of stimuli for initiation of slow excitatory synaptic potentials were analyzed. The only significant differences were found when data from control and oral areas were pooled and compared with combined data from island and anal areas (this assessed differences that could arise from severing nerve fibres running from oral to anal).(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1984

Electrophysiology and enkephalin immunoreactivity of identified myenteric plexus neurones of guinea-pig small intestine.

Intracellular injection of the fluorescent dye, Lucifer Yellow CH, revealed the shapes of neurones in the myenteric plexus of the guinea-pig ileum, and these shapes were correlated with the electrophysiological properties and enkephalin immunoreactivity of the neurones. A total of eighty-three neurones were filled using electrodes containing a 5% solution of the dye. Forty-six cells had many short processes and a single long process (Dogiel type 1) and twenty-four cells had essentially smooth somas and one to eight long processes (Dogiel type II). Thirteen cells could not be put into either group. Enkephalin-like immunoreactivity was detected in twenty-two of the forty-six Dogiel type I cells. Eighteen of these had club-like short processes. No other cells of the eighty-three showed enkephalin-like immunoreactivity. Electrodes filled with a 0.5% solution of Lucifer Yellow in 0.5 M-KCl were used to record from and simultaneously to inject dye into 240 neurones. Eighty-six nerve cells had a slow after-hyperpolarization following the action potential (AH cells) and forty-six nerve cells had no after-hyperpolarization but exhibited a fast excitatory synaptic potential (S cells). The other cells could not be unequivocally identified by their observed electrophysiological characteristics. Almost all S cells (forty-two of forty-six) were Dogiel type I, while eighty-two of the eighty-six AH cells were Dogiel type II. Fifty S cells (eight located geometrically, forty-two by dye injection) and ninety-one AH cells (twenty-six located geometrically, sixty-five by dye injection) were examined for enkephalin immunoreactivity. Fifteen of the S cells were reactive, whereas all of the AH cells were unreactive. It appears that prolonged impalements reduce immunoreactivity so that the proportion of reactive neurones in this series is an underestimate of the true proportion of S cells with enkephalin-like immunoreactivity. The results suggest that a substantial proportion of the S cells in myenteric ganglia contain enkephalin immunoreactivity while none of the AH cells do. The enkephalin neurones have a distinctive shape and are all Dogiel type I cells. AH cells are nearly always Dogiel type II.

Action Potentials↗
PubMed1984

Some effects of lead at mammalian neuromuscular junction.

The effect of lead on transmitter release was investigated in a rat phrenic nerve-hemidiaphragm preparation using conventional microelectrode techniques. Lead reduced the number of quanta released by a nerve stimulus (m) in a dose-dependent fashion. As extracellular Ca2+ concentration ([Ca2+]o) was varied in the absence of lead, a linear relationship between ln(m) and ln([Ca2+]o) was obtained. Lead shifted the relationship between ln(m) and ln([Ca2+]o) to the right without altering the slope. This suggested lead competed with Ca2+, which was confirmed by using a modified Lineweaver-Burk plot. Lead inhibits Ca2+ entry into frog sympathetic preganglionic nerve terminals, and a similar mechanism may underlie this present finding; such a mechanism, however, could not explain all the observed actions of lead. Lead increased the frequency of spontaneous quantal release in a dose-dependent manner, and 10(-4) M lead doubled the magnitude of facilitation of evoked release seen with five stimuli at 60 Hz. It is suggested that these effects result from inhibition of some, or all, of the nerve terminal's Ca2+ sequestration mechanisms.

Animals↗
PubMed1982

The dual effects of GABA and related amino acids on the electrical threshold of ventral horn group Ia afferent terminations in the cat.

Amino acids were administered microelectrophoretically near the unmyelinated terminations of extensor muscle Ia afferent terminations stimulated electrically in the vicinity of lumbar motoneurones in anaesthetized cats. The predominant effect of one group (structurally related to GABA, poor substrates for in vitro amino acid uptake systems) was a reduction in the threshold (depolarization). The second group (including GABA and structural analogues which are substrates for GABA transport systems in vitro) had biphasic effects, an initial reduction being followed by an increase in threshold. The third group (structurally unrelated to GABA, substrates for amino acid uptake systems) only increased Ia termination thresholds. Reductions in termination thresholds, but not increases, were associated with diminution of synaptically evoked primary afferent depolarization, and were decreased by bicuculline methochloride. Many amino acids increased the electrical resistance of the intraspinal medium near the orifices of the barrels of seven barrel micropipettes, and for L-histidine, one of the third group of amino acids, both this effect and the increased threshold of terminations were reversibly modified by microelectrophoretic ouabain. These observations suggest that GABA-mimetics depolarize Ia terminations by interacting with bicuculline-sensitive receptors similar to those at hyperpolarizing gabergic synapses upon spinal interneurones. In addition, under the experimental conditions used, these and other amino acids increase termination thresholds, probably in the absence of any change in membrane conductance, an effect resulting from alterations in the ionic constitution of the extracellular medium around the orifices of micropipettes ejecting amino acids consequent upon the ouabain-sensitive co-transport of amino acids and sodium ions into neurones and glia.

Afferent Pathways↗
PubMed1981

Effects of stimulation on the multiquantal spontaneous synaptic potentials in guinea pig hypogastric ganglia.

Loss frequency (0.5-2 Hz) stimulation of the preganglionic nerve produced calcium ion (Ca2+)-dependent increases in the frequency of spontaneous synaptic potentials recorded from guinea-pig hypogastric ganglion cells. The increased frequency was accompanied by a marked increase in the proportion of multiquantal spontaneous potentials and this was also dependent on extracellular Ca2+. The latter effect was interpreted as an increase in the degree of bursting within the spontaneous release process, supporting the hypothesis that the bursting is related to the cytoplasmic Ca2+ concentration.

Animals↗
PubMed1981

Selective effects of (-)-baclofen on spinal synaptic transmission in the cat.

When ejected microelectrophoretically near spinal interneurones of cats anaesthetised with pentobarbitone and under conditions where postsynaptic excitability was maintained artificially at a constant level, (-), but not (+), -baclofen selectively reduced monosynaptic excitation by impulses in low threshold muscle (Ia and Ib) and cutaneous (Aalpha) afferents. Polysynaptic excitation of interneurones and Renshaw cells by impulses in higher threshold afferents was less affected, and baclofen had little or no effect on the cholinergic monosynaptic excitation of Renshaw cells. Glycinergic and gabergic inhibitions of spinal neurones were relatively insensitive to baclofen. These stereospecific actions of baclofen, produced by either a reduction in the release of excitatory transmitter or postsynaptic antagonism, suggest that Ia, Ib, and Aalpha afferents may release the same excitatory transmitter which differs from that of spinal excitatory interneurones. Microelectrophoretic (-), but not (+), -baclofen also reduced primary afferent depolarization of ventral horn Ia extensor afferent terminations produced by impulses in low threshold flexor afferents, without altering either the electrical excitability of the terminations or their depolarization by electrophoretic GABA or L-glutamate. This stereospecific action of baclofen is interpreted as a reduction in the release of GABA at depolarizing axo-axonic synapses on Ia terminals.

Action Potentials↗