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Biomedical subjects

J I Hubbard

Publications and source records attributed to J I Hubbard.

At least 55 records · Page 3Linked to original sources
PubMed1980

Cell responses evoked by tooth pulp stimulation above the marginal layer of the cat's trigeminal nucleus caudalis.

In cats anesthetized with urethane, all-or-nothing, synaptically evoked recordings were made from 80 separate units in the descending spinal tract of the trigeminal nerve above the left trigeminal nucleus caudalis, at depths not exceeding 50 micrometer from the surface of the medulla. The units were excited by the left upper (21), left lower (25), either (28), or only on simultaneous stimulation of both (six) canine tooth pulps. There was no somototopic distribution. The latency of responses ranged from 4 to 82 msec. For the group of 28 units excited by upper and lower tooth pulps, there was close matching of response latencies from the two teeth. An abrupt decrease in latency upon increasing stimulation strength ("jumping"), and a gradual increase in latency during repetitive stimulation at a frequency between 1 and 20 Hz ("drifting") was characteristic of most, but not all, responses. Units evoked by stimulation of the inferior dental or infraorbital nerves had similar characteristics. Stimulation of a tooth pulp at threshold for a particular unit was used to test the excitability of that unit after suprathreshold stimulation of the same or a different canine tooth pulp. Stimulation of the upper left canine tooth pulp was generally only facilitatory, while stimulation of the lower left canine tooth pulp was initially facilitatory and later inhibitory. Stimulation of the upper or lower right canine tooth pulps did not excite but could inhibit units excited by the left canine tooth pulps. There was a significant correlation between the frequency at which a unit would follow repetitive stimulation and the duration of the inhibition generated by the first of a pair of stimuli. Long inhibition was associated with poor frequency following.

Animals↗
PubMed1980

Excitation and inhibition of marginal layer and interstitial interneurons in cat nucleus caudalis by mechanical stimuli.

In cats anesthetized with urethane, the caudal medulla was stabilized in preparation for intracellular recording from interstitial neurons in the descending tract of the trigeminal nerve and from neurons in lamina I of nucleus caudalis. Glass micropipets (10-50 M ohms) were advanced from the surface to a maximum depth of 350 micrometer. When DC potential shifts occurred, it was found that mechanical stimuli to the face generated bursts of positive-going spikes, followed in some cases by inhibitory postsynaptic potentials (IPSPs). Subdermal electrical stimulation of the face in each receptive field almost always enabled the same neuron to be driven electrically. Recordings were classified as from primary afferent fibers or from interneurons. Primary fibers had a purely positive spike, with a latency varying by no more than 0.05 msec, and could follow stimulation at 500 Hz. The mean latency for the fibers was 1.87 +/- 0.06 msec (n=75), and their absolute refractory period was 0.42 +/- 0.02 msec (n=36). Recordings were classed as from interneurons if there was an IPSP or the latency was at least 4 msec, with a variation of latency of at lest 0.5 msec. Responses thought to be monosynaptically driven had a mean latency of 2.09 +/0 0.07 msec (n=32) and could follow pairs of stimuli at a mean minimum interval of 0.70 +/- 0.06 msec (n=20). Responses thought to be polysynaptically driven had a mean latency of 7.9 +/- 1.08 msec (n=49) and a mean interstimulus interval of 2.96 +/- 0.84 (n=20). Most responses were generated by brushing the face (n=87), some by pressure on the face (n=25), and a few by pinching the skin of the face (n=6). Interneuron responses were most commonly recorded in the first 200 micrometer of the descending tract, and this position was confirmed by the injection of pontamine sky blue and the examination of frozen sections. The recordings were thought to be from dendrites of marginal and interstitial cells or the somas of interstitial cells. The IPSPs which followed spike potentials could only follow stimuli at 10 Hz or less. The failure appeared to be at a primary afferent synapse upon an inhibitory interneuron. Collision tests between mechanically evoked and electrically evoked responses showed long-lasting inhibition of the response to electrical stimulation after collision. Presynaptic inhibition exerted on the primary afferent excitation was suggested as the explanation.

Animals↗
PubMed1979

Brain angiotensin II binding and central [Sar1,Ala8]angiotensin responses in normal rats and the New Zealand strain of genetically hypertensive rats.

1. Specific angiotensin II (ANGII) receptor binding was measured in regions of the brains of the New Zealand gentically hypertensive and normal rats. 2. ANGII receptor binding was consistently lower in the septum, midbrain, thalamus and posterior medulla of the genetically hypertensive rats than in normal rats. 3. Blood pressure responses to intraventricular injections of ANGII and an ANGII antagonist [Sar1,Ala8]angiotensin were studied in conscious and pentobarbitone-anaesthetized genetically hypertensive and normal rats. In conscious rats no significant difference between the two strains of rat was detected. 4. In pentobarbitone-anaesthetized rats intraventricular injection of 40 microgram of [Sar1,Ala8]angiotensin had a hypotensive effect which was three times greater in the genetically hypertensive rats than that observed in normal rats. The latency of this hypotensive effect was longer than the latency of the hypertensive effect of ANGII. 5. The drinking responses to intraventricular injections of ANGII were similar in genetically hypertensive and normal rats. 6. The physiological role of the ANGII system is discussed and it is concluded that an abnormality of this system in the brain may well be responsible for the hypertension found in the genetically hypertensive rat.

Angiotensin II↗
PubMed1979

The neuronal organization of the rat subfornical organ in vitro and a test of the osmo- and morphine-receptor hypotheses.

1. Extracellular action potentials (units) were recorded from rat subfornical organ explants in vitro in response to addition of angiotensin II (AII) or carbamyl-choline (carbachol) or serotonin (5-HT) to the superfusion solution. The frequency recorded was dose dependent over a wide range (AII, 0.05--5 nM; carbachol, 2.7--2700 nM; 5-HT, 1--100 nM). Appropriate antagonists, sarc1-ala2 angiotensin (saralasin) for AII, atropine sulphate for carbachol and methysergide maleate for 5-HT, blocked these excitations. The effects were reversible except for that of atropine. 2. Two populations of AII-excited units were found. A superficial population lying between 15 and 45 microns from the ependymal surface was blocked only by saralasin and another population lying more than 55 microns below the ependymal surface could be blocked by atropine as well as saralasin. Carbachol-evoked units generally lay below 45 microns, and 5-HT-evoked units were scattered evenly over the subfornical organ. It is suggested that superficial AII-excited neurones have a cholinergic excitatory synapse with the deeper carbachol-excited neurones. 3. No evidence was found for the hypothesis that neurones of the subfornical organ are excited by morphine or by changes in extracellular osmotic pressure. 4. All types of drug-excited unit, both superficial (15--55 microns) and deep (below 55 microns), could be driven polysynaptically from the body or columns of the fornix. Units driven antidromically or antidromically and synaptically were almost all more than 55 microns from the surface. 5-HT-evoked units were driven antidromically only by stimulation of the columns of the fornix. AII- and carbachol-evoked units could be driven antidromically or antidromically and synaptically by stimulation of the body or the columns of the fornix. It is suggested that AII units driven antidromically are actually carbachol-sensitive neurones driven by the more superficial AII-sensitive cells. 5. A model of the neuronal organization of the subfornical organ is suggested in which AII-sensitive neurones lying superficially are excited by substances borne by blood or cerebrospinal fluid and synapse with deeper carbachol-sensitive neurones. The axons of these deep neurones pass out of the subfornical organ in the columns and body of the fornix. Afferent fibres from the body and columns of the fornix polysynaptically excite both superficial and deep neurones. A recurrent inhibitory circuit is suggested on the output path.

Action Potentials↗
PubMed1979

Responses in the diagonal band of Broca evoked by stimulation of the fornix in the cat.

1. Field potentials were recorded within the boundaries of the septal component of the diagonal band of Broca following stimulation of the fornix. The position of the recording electrode was marked by pressure injection of Alcian blue dye. 2. Stimulation of the medial aspect of the ipsilateral fornix produced a simple field caudally consisting of a short duration, short latency negative wave (N1) and a later small prolonged positive wave (P1). It is suggested that N1 is due to antidromic activation of the cells and P1 to their recurrent inhibition. 3. In the rostral part of the septal component of the diagonal band of Broca the field pattern was more complex, containing, in addition to N1 and P1, further negative waves, N2 and N3. N2 was compounded of antidromically and synaptically evoked components and N3 was associated with monosynaptic excitation of the cells. 4. Stimulation of the lateral margin of the fornix was shown to excite antidromically and synaptically the same cells as were excited by stimulation of the medial aspect of the fornix. 5. Stimulation of the medial and lateral aspects of contralateral fornix generated positive waves of similar character to P1. 6. Intracarotid injection of hyperosmotic saline solution caused behavioural signs of arousal and inhibition of spontaneous discharge in a third of the units tested. Spontaneously discharging units (mean frequency +/- S.E. of mean, 13.4 +/- 1.8, n = 55) were inhibited by stimulation of the medial and lateral ipsilateral and contralateral fornix. It is suggested that inhibitory interneurones receive contra- and ipsilateral input. Units with these characteristics were found. 7. The septal component of the diagonal band of Broca was compared with other septal nuclei and found to resemble them in its rostral portion in that it has a reciprocal relationship with ventral and dorsal hippocampus. The caudal portion is unique in the cells project to dorsal and ventral hippocampus but there is no reciprocal projection.

Animals↗
PubMed1979

Intracellular recording from neurones of the rat subfornical organ in vitro.

1. Intracellular recordings from neurones in the subfornical organ in vitro showed that there were two classes of neurones. One class lay within 55 micron of the ventricular surface and was synaptically excited but not inhibited by stimulation of the body or columns of the fornix. These neurones could not be excited antidromically. The other class lay more deeply and was antidromically and synaptically excited and inhibited by stimulation of the body and columns of the fornix. 2. The neurones of the subfornical organ appeared to have the characteristics of neurosecretory neurones. Their action potentials were prolonged and their antidromic spike was easily broken down into components by repetitive stimulation. 3. The organization of the subfornical organ inferred from extracellular recording was confirmed by the results of intracellular recording.

Action Potentials↗
PubMed1979

The trophic influence of tetrodotoxin-inactive nerves on normal and reinnervated rat skeletal muscles.

1. Nerve impulses in the rat sciatic nerve were blocked for long periods by tetrodotoxin (TTX) released from capillary implants. The TTX capillaries did not block axonal transport, nor did they cause any sign of nerve degeneration. 2. A comparison of the effects of TTX paralysis and denervation was made on both extensor digitorium longus (e.d.l.) and soleus muscles over 21 days, a time when the products of nerve degeneration were unlikely to contribute to the changes associated with denervation. The resting membrane potential of TTX-paralysed muscles was significantly different (P less than 0.005) from that of the denervated muscles at all periods and at 21 days the decrease that can be attributed to inactivity was 61% (e.d.l.) and 49% (soleus) of that which follows denervation. This disparity was even more pronounced for the ACh receptor density where the increase in receptors due to inactivity was only 34% (e.d.l.) and 21% (soleus) of that due to denervation. 3. A similar comparison was made on muscles which had been reinnervated by TTX-inactive nerves. These muscles were found to have a significantly higher resting membrane potential and lower ACh receptor density than the denervated muscles (P less than 0.05). 4. The experiments on reinnervated muscles preclude the possibility that nerve degeneration products are solely responsible for the difference between the TTX-paralysed and denervated muscles and suggest that the difference can be attributed to the trophic influence of the nerve. 5. An observed increase in the m.e.p.p. frequency of the TTX-paralysed muscles indicated that nerve action potentials play a role in regulating the spontaneous release from nerve terminals.

Acetylcholine↗
PubMed1977

Distribution of angiotensin II receptors in rat brain.

Angiotensin II binding activity of rat brain particles was examined using [125I]-angiotensin II (0.1-0.3 nM) in the presence and absence of excess unlabelled angiotensin II. Certain features of the binding suggested that physiological receptors were involved. The binding activity was temperature dependent and was increased 3-fold by the addition of 0.5 M EDTA. The binding appeared specific as judged by inhibition with angiotensin II agonists and antagonists. The "specific" binding was saturable, two-thirds reversible and occurred with high affinity. The equilibrium dissociation constant (Kd) of the "specific" binding was 0.9 nM. Subcellular fractionation studies indicated that over 90% of the binding was associated with particulate matter and was concentrated in the crude microsomal fraction. Binding was localized to the midbrain, thalamus, septum, hypothalamus and medulla; Very low levels of binding were found in the cortex, hippocampus and striatum; The lateral septum had the highest binding activity of all the tissues examined. Subdivision of the medulla showed that the highest binding activity was associated with the area postrema and medullary regions ventral to this organ.

Angiotensin II↗
PubMed1976

The membrane potential of rat diaphragm muscle fibres and the effect of denervation.

1. Resting membrane potentials of rat diaphragm muscles were measured in vitro after previous denervation for 0-10 days. In some experiments denervated muscles were incubated in vitro for 3 hr while in others they were cultured for 15-24 hr to allow adequate exposure to drugs before recording. 2. It was found that resting membrane potentials, within 2-5 mm of the site of nerve section were significantly lower, within 3 hr, than resting membrane potentials measured more than 9 mm away from site of nerve section. This difference could be reduced or abolished by bathing preparations in solutions containing adrenaline (10 muM), noradrenaline (10 muM) or isoprenaline (10 muM) or dibutyryl cyclic AMP (10 muM-0-25 mM in the presence of 2 mM theophylline). Cyclic AMP (0-5 mM) was ineffective. 3. Application of solutions containing dibutyryl cyclic AMP for 3 hr also raised the resting membrane potential of muscles denervated 4-5 days previously. Culture studies showed that this effect was sustained when the time of incubation was 24 hr. 4. Incubating freshly denervated preparations with cycloheximide (22 mug/ml.) or actinomycin D (1 mug/ml.) did not prevent the development of the early (3 hr) fall in resting membrane potential despite a concomitant inhibition of RNA or protein synthesis. Culturing freshly denervated muscles in solutions containing cycloheximide (10 or 25 mug/ml.) which blocked 93% of protein synthesis, did not prevent the expected drop in resting membrane potential after 15 or 24 hr. 5. It was found that exposure to ouabain (1 or 5 mM) produced a rapid (15 min) fall in resting membrane potential in innervated and denervated preparations treated with dibutyryl cyclic AMP but not denervated preparations. After 5 days denervation cyclic AMP levels in muscle were increased by about 40%. 6. It is suggested that upon denervation an electrogenic action of a NA+-pump is blocked and that dibutyryl cyclic AMP and catecholamines are capable of stimulating this pump.

Animals↗
PubMed1973

Neuromuscular transmission in a mammalian preparation in the absence of blocking drugs and the effect of D-tubocurarine.

1. Neuromuscular transmission in the presence and absence of D-tubocurarine was examined in cut muscle preparations of the rat diaphragm using intracellular recording techniques. The method of localizing the end-plates is described and evidence is presented indicating that end-plate potential (e.p.p.) recordings were made close to the end-plate region and that reliable estimates of the quantum content of e.p.p.s could be made.2. During repetitive nerve stimulation at rates between 2 and 10 Hz, e.p.p. amplitudes declined in response to the first 6-8 stimuli to reach a plateau level which was maintained for 1500 stimuli. At higher rates of stimulation some 500-700 stimuli were needed before a plateau level of amplitude was reached. It was demonstrated that these amplitude changes reflected similar changes in the quantal release of ACh.3. Tubocurarine in a concentration of 4 x 10(-8) g/ml. had no effect on quantal release but did reduce quantal size. In the presence of tubocurarine, 8 x 10(-8) g/ml., small reductions in the quantum content of the first e.p.p. in response to a train of stimuli and the maintained quantal release were observed. In the presence of tubocurarine 4 x 10(-7) g/ml., the quantum content of the first e.p.p. and the maintained release were further reduced, to the level previously described for curarized preparations. At this concentration a significant effect of tubocurarine upon the presynaptic measurements could be detected (t test). Studies on single junctions revealed that the post- and presynaptic effects of tubocurarine developed with different time courses.4. Neuromuscular preparations in vivo have been reported to be much more resistant to maintatined stimulation than curarized neuromuscular preparations in vitro. It is suggested that this disparity is explained by the presynaptic action of tubocurarine.5. From the quantal release rates of the present investigation and reports of ACh release/stimulus/end-plate in previous investigations it can be calculated that a quantum of ACh contains between 12,000 and 21,000 molecules.

Acetylcholine↗
PubMed1973

Spontaneous quantal transmitter release: a statistical analysis and some implications.

1. Miniature end-plate potentials (m.e.p.p.s) were intra- and extracellularly recorded from neuromuscular junctions in rat phrenic nerve-diaphragm preparations in vitro.2. Statistical analysis of the intervals between m.e.p.p.s showed that when the mean number of events in time t was plotted as a function of the variance of the events in time t there was a significant deviation from the straight line relationship expected for a Poisson process. Computer simulation showed that this deviation is explicable if release was generated by the random phasing of the activity of a number of releasing sites.3. There was no indication that release of one quantum influences the probability of release of remaining quanta (drag, clustering). It is suggested that m.e.p.p.s whose amplitude is larger than the mode result from the release of the contents of vesicles whose volume is also supramodal.4. The effects of depolarization of nerve terminals upon the variance-mean curve suggest an increase in the activity of sites rather than an increase in their number.5. Statistical analysis indicated at least 200 +/- 100 (mean +/- 1 S.E.) releasing sites. This number is of the same order as the number of sites of vesicle aggregation and presynaptic membrane density seen in electron micrographs of nerve terminals of this preparation.

Animals↗