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Biomedical subjects

T W Ford

Publications and source records attributed to T W Ford.

At least 19 recordsLinked to original sources
PubMed2007

The respiratory drive to thoracic motoneurones in the cat and its relation to the connections from expiratory bulbospinal neurones.

The descending control of respiratory-related motoneurones in the thoracic spinal cord remains the subject of some debate. In this study, direct connections from expiratory bulbospinal neurones to identified motoneurones were investigated using spike-triggered averaging and the strengths of connection revealed were related to the presence and size of central respiratory drive potentials in the same motoneurones. Intracellular recordings were made from motoneurones in segments T5-T9 of the spinal cord of anaesthetized cats. Spike-triggered averaging from expiratory bulbospinal neurones in the caudal medulla revealed monosynaptic EPSPs in all groups of motoneurones, with the strongest connections to expiratory motoneurones with axons in the internal intercostal nerve. In the latter, connection strength was similar irrespective of the target muscle (e.g. external abdominal oblique or internal intercostal) and the EPSP amplitude was positively correlated with the amplitude of the central respiratory drive potential of the motoneurone. For this group, EPSPs were found in 45/83 bulbospinal neurone/motoneurone pairs, with a mean amplitude of 40.5 microV. The overall strength of the connection supports previous measurements made by cross-correlation, but is about 10 times stronger than that reported in the only previous similar survey to use spike-triggered averaging. Calculations are presented to suggest that this input alone is sufficient to account for all the expiratory depolarization seen in the recorded motoneurones. However, extra sources of input, or amplification of this one, are likely to be necessary to produce a useful motoneurone output.

Action Potentials↗
PubMed2006

Respiratory drive in hindlimb motoneurones of the anaesthetized female cat.

Anatomical studies have shown a monosynaptic projection from nucleus retroambiguus (NRA) to semimembranosus (Sm) motor nucleus in female cats, which is stronger in oestrus. Expiratory bulbospinal neurones are the best documented functional cell type in the NRA. If these cells participate in this projection, an expiratory drive would be expected in Sm motoneurones and this drive would be expected to be stronger in oestrus. In anaesthetized, paralyzed, ovariohysterectomized female cats, artificially ventilated to produce a strong respiratory drive (as monitored by phrenic nerve discharges), intracellular recordings were made from Sm motoneurones and from motoneurones in the surrounding hindlimb motor nuclei that are outside the focus of the NRA projection. The animals comprised two groups: either treated for 7 days with oestradiol benzoate (oestrous) or untreated (non-oestrous). Central respiratory drive potentials (CRDPs) were observed in most motoneurones of both groups, with amplitudes larger for the oestrous than for the non-oestrous group (1.58+/-1.34 mV versus 0.89+/-0.79 mV, mean+/-S.D.). However, the CRDPs most often consisted of a maximum depolarization in early expiration, which declined in late expiration and into inspiration. This pattern is different from the incrementing firing pattern of most expiratory bulbospinal neurones. The CRDPs in Sm and semitendinosus motoneurones (located in the same motor column) were of similar size and frequency to CRDPs in motoneurones outside that column. The hypothesis that expiratory bulbospinal neurones are significantly involved in the projection was rejected. Alternative sources and possible functional roles for the CRDPs are discussed.

Action Potentials↗
PubMed2005

Functional heterogeneity among neurons in the nucleus retroambiguus with lumbosacral projections in female cats.

Nucleus retroambiguus (NRA), in the caudal medulla, projects to all spinal levels. One physiological role is abdominal pressure control, evidenced by projections to intercostal and abdominal motoneurons from expiratory bulbospinal neurons (EBSNs) within NRA. The roles of NRA projections to the lumbosacral cord are less certain, although those to limb motoneurons may relate to mating behavior and those to Onuf's nucleus (ON) to maintaining continence. To clarify this we physiologically characterized NRA projections to the lumbosacral cord. Extracellular recordings were made in NRA under anesthesia and paralysis in estrus cats. Administered CO(2) gave a strong respiratory drive. Antidromic unit responses were recorded to stimulation of the contralateral ventrolateral funiculus of L(6), L(7), or sacral segments and to microstimulation in the region of semimembranosus motor nucleus or ON. All units were found at sites showing expiratory discharges. Units that showed collisions between antidromic and spontaneous spikes (all in late expiration) were identified as EBSNs. These were common from the ventrolateral funiculus (VLF) of L(6) (42.5%) or L(7) (32.9%), but rare from the sacral VLF or the motor nuclei. Antidromic latencies revealed a subthreshold respiratory drive in some non-EBSNs. This group had lower conduction velocities than the EBSNs. The remainder, with a negligible respiratory drive, had even lower conduction velocities. A new population of NRA neurons has thus been defined. They are not active even with a strong respiratory drive, but may provide most of the synaptic input from NRA to lower lumbar and sacral segments and could subserve functions related to mating behavior.

Action Potentials↗
PubMed2002

Plateau potentials in hindlimb motoneurones of female cats under anaesthesia.

Central respiratory drive potentials (CRDPs) were observed in intracellular recordings from hindlimb motoneurones of anaesthetized, paralysed, ovariohysterectomized female cats, artificially ventilated so as to have a strong respiratory drive under hyperoxic hypercapnea. The animals comprised two groups: three animals treated for 7 days with oestradiol benzoate (oestrous), and three untreated (non-oestrous). Several features of the CRDPs suggested the involvement of voltage-sensitive channels, including variability in the CRDP amplitude and potentiation of the CRDP by depolarizing currents. Clear plateau potentials, related to or triggered by depolarizing phases of the CRDPs, occurred in six motoneurones, three in response to depolarizing currents, three spontaneously. This is the first report of plateau potentials in mammalian motoneurones under anaesthesia. The mechanisms accessed here by the respiratory inputs are deduced to be particularly potent, perhaps because of a distal dendritic location. Plateau-like effects were more common in the oestrous animals, which suggests a specific role for the plateau potentials in the production of the stereotyped movements of female receptive behaviour.

Action Potentials↗
PubMed2000

Changes in the distribution of synaptic potentials from bulbospinal neurones following axotomy in cat thoracic spinal cord.

1. Plasticity in functional connections of expiratory bulbospinal neurones was investigated by measurement of terminal potentials (TPs) and focal synaptic potentials (FSPs), recorded with spike-triggered averaging in the thoracic spinal cord of anaesthetized, paralysed cats. These measurements were made in normal cats and in those which had previously been subjected to spinal cord lesions that transected the axons of the bulbospinal neurones in the segment below that under investigation, either about 2 weeks or about 16 weeks previously. 2. In both groups of operated animals bulbospinal neurones with firing properties and conduction velocities similar to normal were present. The extracellular recordings that were averaged to reveal TPs and FSPs were made on two standard grids, each consisting of eight sites spaced 0.25 mm apart on two electrode tracks. One grid was positioned at a rostral and one at a caudal location within one segment (T7-T9). 3. Tn the normal animals TPs and FSPs were larger and/or more common at rostral sites than at caudal sites, by a factor of about 1.7. In both 2 week and 16 week animals, TPs and FSPs were observed, both showing normal tine courses and latencies. At rostral sites in 2 week and 16 week animals the amplitudes and/or the frequency of occurrence of TPs and FSPs were similar to normal, as was the case fir caudal sites in the 2 week animals. However, at caudal sites in the 16 week animals the FSPs were mole common and/or significantly larger than normal, with the increase particularly marked on the lateral track, being equivalent to a factor of about 2. A corresponding increase in the amplitude and/or frequency of occurrence of TPs at caudal lateral sites was also seen, but was not significant. 4. The results are interpreted as evidence for short-range sprouting of the bulbospinal axons and the formation by them of new connections in the caudal parts of the segments concerned.

Animals↗
PubMed1999

Activity of aortic chemoreceptors in the anaesthetized rat.

1. It has been widely accepted that the rat aortic depressor nerve contains only baroreceptors. However, the experiments which have provided these negative data have employed whole aortic nerve recording. In the present study, the technical difficulties associated with recording single fibres in vivo, from the rat aortic nerve (diameter 25-50 microm), have been surmounted using a small tip, glass suction electrode technique. 2. Upon switching from normocapnic hyperoxia to hypercapnic hypoxia, irregularly firing units (n = 13) appeared and these were significantly excited by intravenous injections of sodium cyanide (20 microg) but not by rises in arterial blood pressure induced by methoxamine (an alpha1-adrenoreceptor agonist; 10 microg). Inhalation of 100 % oxygen rapidly and reversibly silenced, or profoundly reduced, ongoing activity. 3. Intravenous injection of phenylbiguanide (PBG; a 5-HT3 receptor agonist; 8 microg) strongly stimulated the chemoreceptors and was followed by a period of chemodepression (3-21 s). In contrast none of the single fibre baroreceptors recorded (n = 15) were excited by PBG but all significantly increased their discharge in response to the increases in arterial blood pressure associated with methoxamine and cyanide. Both the excitatory and inhibitory effects of PBG on the chemoreceptor fibres were abolished by ondansetron (a 5-HT3 receptor antagonist: 1 mg kg-1 i.v.; n = 5 animals) whilst the chemoexcitatory action of cyanide was preserved. 4. It is concluded that there are chemoreceptor afferents contained in the aortic nerve of the Sprague-Dawley rat. The 5-HT3 receptor appears not to be a pre-requisite for aortic body chemoexcitation.

Anesthesia↗
PubMed1992

Prolonged potentiation of transmission through a withdrawal reflex pathway after noxious stimulation of the heel in the rabbit.

The sural-gastrocnemius reflex of the spinalized rabbit was potentiated to an average of 3-6 times control levels after the application of noxious mechanical, thermal or chemical stimuli to the skin of the heel. Facilitation of the reflex was maximal within 1 min of the noxious stimulus, and in many cases persisted for more than 1 h. Prolonged increases in the excitability of the sural-gastrocnemius reflex were not seen after innocuous mechanical or thermal stimulation of the heel. Repetitive electrical stimulation of the sural nerve (100 shocks given at 0.5 Hz) caused persistent facilitation of the reflex when small myelinated A delta fibres or non-myelinated C-fibres were recruited by the conditioning stimulus. Such protracted increases in the excitability of the sural-gastrocnemius pathway would enhance the protective functions of this reflex. The mechanisms described here have probably evolved to provide a high level of reflex protection to the heel after tissue damage has occurred at that site.

Animals↗
PubMed1992

Opioidergic inhibition of flexor and extensor reflexes in the rabbit.

1. Recordings were made from gastrocnemius medialis (GM), semitendinosus (ST) and tibialis anterior/extensor digitorum longus (TA/EDL) motor nerves during mechanical and electrical stimulation of the skin of the foot in decerebrated and spinalized rabbits. 2. GM motoneurones were excited from the heel and not from the toes, whereas TA/EDL responded to stimulation at the toes but not at the heel. ST also responded to electrical and mechanical stimulation at the toes, but there was a disparity between the effects of the two types of stimuli when they were applied at the heel: ST motoneurones fired in response to electrical stimulation of the heel but showed only an 'off' response to mechanical stimulation at this site. 3. The opioid antagonist naloxone caused a dose-dependent increase in all reflexes evoked by electrical stimulation of the skin. The heel-GM, toes-ST and toes-TA/EDL reflexes all increased to more than 3 times control levels with naloxone, which also caused significant decreases in the latencies of these reflex responses. On the other hand, the heel-ST response increased to just 1.4 times control levels and showed no decrease in latency with the opioid antagonist. 4. These data suggest that segmental withdrawal reflex pathways in the rabbit are suppressed by endogenous opioid peptides. This opioid-mediated inhibition seems to operate non-selectively on reflex pathways between cutaneous afferents and motoneurones.

Animals↗
PubMed1991

Soft X-ray contact microscopy of biological materials.

Light microscopy (LM) enables biological specimens to be examined without fixation or dehydration but the resolution is insufficient for studies of cell ultrastructure. Electron microscopy (EM) improves the resolution, but requires the specimen to be fixed or frozen, which may cause alterations in cell structure. Using soft X-rays to image specimens improves the resolution, relative to LM, and avoids tissue pretreatment. Staining is not required since within the 'water window' (2.3-4.4 nm), carbon absorbs more strongly than oxygen. The lower attenuation of soft X-rays, relative to electrons, by biological material allows specimens several microns thick to be examined. Several sources for generating water-window X-rays are briefly described and examples of images obtained with each are presented. The specimens imaged include both plant and animal material either in the fixed or natural state. Of the different systems currently used to collect images only contact imaging is considered in detail. By placing the specimen against photosensitive resist, which acts as the image recording medium, an absorption map of the specimen is produced. This latent image is then chemically developed and, after coating, the resist is examined by scanning EM, or, if a replica is produced, by transmission EM. Using laser-produced plasmas such images are produced within a very short exposure time, typically 1-10 nsec, thus avoiding any radiation-induced damage to the specimen which other X-ray imaging techniques may cause.

Animals↗
PubMed1991

Opioidergic inhibition of reflexes evoked by selective stimulation of sural nerve C fibres in the rabbit.

Reflexes were evoked in the gastrocnemius medialis (GM) muscle nerve by selective electrical stimulation of the non-myelinated C fibres of the ipsilateral sural nerve of decerebrated, spinalized rabbits. The opioid antagonist (-)-quadazocine (555 micrograms/kg i.v.) enhanced responses to sural C fibre stimulation to an average of 236% of pre-drug levels. In addition, C fibre-evoked reflexes were depressed for 7-9 min after repetitive activation of the high threshold axons of the common peroneal nerve, and this effect was reversed after quadazocine. Thus, GM responses to stimulation of non-myelinated sural afferent fibres are suppressed by endogenous opioid peptides, but the degree of inhibition does not appear to be as profound as that previously reported for reflexes evoked by myelinated fibres.

Animals↗
PubMed1991

Prolonged inhibition of a spinal reflex after intense stimulation of distant peripheral nerves in the decerebrated rabbit.

1. In decerebrated rabbits, repetitive stimulation of the high-threshold afferents of the left common peroneal (CP) nerve evokes prolonged depression of the sural-gastrocnemius medialis (GM) reflex recorded in the same limb. This inhibition is antagonized by co-administration of the opioid antagonist naloxone with the alpha 2-adrenoceptor antagonist idazoxan. The present study was designed to investigate whether such inhibition could be elicited from the contralateral hindlimb or the forelimbs. 2. The sural-GM reflex of decerebrated rabbits was depressed for more than 15 min after stimulation of either ipsilateral or contralateral common peroneal (CP) or median nerves with 500 pulses of 20 V, 1 ms given at 5 Hz. The order of efficacy for generating this inhibition was ipsilateral CP greater than contralateral CP greater than or equal to ipsilateral median = contralateral median. In three of thirty-nine rabbits, stimulation of the median nerves caused facilitation of the sural-GM reflex. 3. Idazoxan (1-2 mg/kg I.V.) did not significantly alter the depressant effect of ipsilateral CP stimulation but reduced that evoked by either median nerve and almost abolished the inhibition evoked from the contralateral CP nerve. 4. Naloxone (0.25 mg/kg I.V.) reduced the effects of ipsilateral CP stimulation, did not alter the inhibition evoked from contralateral CP, and had equivocal actions on the responses to median nerve stimulation. 5. When given together, the two antagonists almost abolished the effects of stimulating the median nerves and the contralateral CP nerve, and markedly reduced the inhibition evoked from the ipsilateral CP nerve. 6. These data show that prolonged inhibition of the sural-GM reflex can be evoked by stimulation of nerves in all four limbs and that in each case the inhibition can be blocked or reduced by co-administration of antagonists to opioid and alpha 2-adrenergic receptors. Such persistent inhibition of reflexes may serve to inhibit withdrawal reflexes in situations where interruptions to normal movement would be disadvantageous.

Adrenergic alpha-Antagonists↗
PubMed1990

Noxious stimulation of the toes evokes long-lasting, naloxone-reversible suppression of the sural-gastrocnemius reflex in the rabbit.

Repetitive stimulation of the small myelinated and non-myelinated afferents of the common peroneal (c.p.) nerve evokes a long-lasting (20-25 min), naloxone-reversible inhibition of the sural-gastrocnemius reflex in the decerebrated and spinalized rabbit. Altering the number and frequency of stimuli applied to the c.p. nerve showed that this inhibition was dependent on temporal summation of afferent input from that nerve, and that the optimum frequency for producing the effect was between 2 and 10 Hz. Application of natural conditioning stimuli in and around the receptive field of the c.p. nerve showed that noxious, but not innocuous, mechanical and thermal stimuli could evoke long-lasting inhibition of the sural-gastrocnemius reflex. Thermal stimuli produced a biphasic change in the excitability of the reflex with facilitation followed by inhibition. The opioid antagonist naloxone (250 micrograms.kg-1) blocked all suppression resulting from these natural noxious stimuli. Chemical stimulation of the skin with mustard oil did not evoke naloxone-reversible inhibition of the reflex. These results indicate that intensely noxious stimuli can promote the release of opioid peptides in the spinal cord, and that one of the functions of these peptides may be to regulate the level of excitability in withdrawal reflex pathways.

Animals↗
PubMed1990

Gender differences in depression in an employment setting.

This study extends the literature on sex differences in depression to an employment setting, using Minnesota Multiphasic Personality Inventory (MMPI; T and raw scores) and Depression (D) 30 measures. In contrast to previous findings, no gender differences remained on any of the measures after the effects of salary, age, education, and job classification had been taken into account. Findings replicated earlier results showing depressed males to have greater difficulty with concentration and motivation than depressed females. Data suggest that MMPI sex-based T-scores may overcorrect for sex differences in raw scores. Possible explanations for the findings are discussed, including a general improvement in women's well-being associated with changes in social conditions such as employment, or the possibility of a self-selection bias in our sample.

Achievement↗
PubMed1990

Neurones in the dorsal motor vagal nucleus of the cat with non-myelinated axons projecting to the heart and lungs.

Extracellular recordings were made from ninety-four single motoneurones in the dorsal motor vagal nucleus of chloralose-anaesthetized or decerebrate cats. Fifty-five neurones had axons in cardiac vagal branches and thirty-nine had axons in pulmonary vagal branches; the conduction velocities of the axons were in the C fibre range, i.e. the axons were non-myelinated. The neurons exhibited little or no spontaneous activity. Excitatory and inhibitory synaptic inputs were demonstrated by electrical stimulation of the vagus nerve or its branches. Twenty-four neurones were tested by carotid sinus distension but only one was excited. Iontophoretic excitation of neurones projecting to cardiac vagal branches had no effect on heart rate. The properties of these neurones and their possible functions are discussed and contrasted with those of cardiac and pulmonary vagal motoneurones in the nucleus ambiguus.

Action Potentials↗
PubMed1989

Activation by high intensity peripheral nerve stimulation of adrenergic and opioidergic inhibition of a spinal reflex in the decerebrated rabbit.

The short-latency sural to gastrocnemius reflex in the decerebrated rabbit was depressed for 20-30 min following high intensity conditioning stimulation of the common peroneal nerve. This effect was observed in animals with or without spinal section, but was greater in non-spinalized preparations. Graded conditioning stimuli showed that it was necessary to activate fine myelinated common peroneal axons to inhibit the reflex. In spinalized rabbits, maximal inhibition was achieved with conditioning stimulation of fine myelinated axons and was completely reversed by the opioid antagonist naloxone. In non-spinalized rabbits, maximal inhibition was only obtained with conditioning stimuli which activated non-myelinated axons. In these preparations the effects of common peroneal nerve stimuli were only blocked by co-administration of naloxone with the alpha 2-adrenoceptor antagonist idazoxan. Thus high intensity peripheral nerve stimuli activated a segmental opioidergic and a supraspinal adrenergic suppression of the sural-gastrocnemius withdrawal reflex. Such long-lasting suppression of reflex excitability may contribute to recovery from intensely noxious stimuli.

Action Potentials↗
PubMed1989

Reflex actions of selective stimulation of sural nerve C fibres in the rabbit.

Selective electrical stimulation of the non-myelinated C fibres of the sural nerve in the decerebrated, spinalized rabbit evoked long-latency (76-160 ms), long-lasting (greater than 100 ms) reflex responses in the ipsilateral ankle extensor gastrocnemius medialis (GM). Activation of the same fibres elicited little or no response from the ipsilateral knee flexor semitendinosus (ST). Reflex responses were evoked in both GM and ST muscle nerves by stimulation of the A beta afferents of the sural nerve. The A beta-elicited reflex in GM was enhanced, and that in ST depressed by prior activation of sural nerve C fibres. Strychnine, but not picrotoxin or mecamylamine, blocked C fibre-induced inhibition of the flexor reflex. Pinching the heel with serrated forceps produced an immediate reflex discharge in GM motoneurones, whereas ST responded upon termination of the stimulus. Pinching the second toe evoked reflex activity in ST but not in GM. After strychnine (0.5 mg kg-1), both sets of motoneurones responded simultaneously to stimulation of either the heel or the toe. These data show that sural and other afferent fibres from the heel excite ipsilateral GM motoneurones and inhibit ST reflex responses. One interpretation of these findings is that fine sural afferents activate parallel inhibitory and excitatory pathways, of which the former is sensitive to strychnine and therefore probably mediated by glycine.

Afferent Pathways↗
PubMed1988

Thyrotropin releasing hormone, cholecystokinin and endogenous opioids in the modulation of spinal reflexes in the rabbit.

Electrical stimulation of the sural nerve of the rabbit evokes reflexes in the ipsilateral ankle extensor gastrocnemius medialis and in the knee flexor semitendinosus which are differentially modulated by endogenous opioids. Intravenous injection of the putative functional opioid antagonist, thyrotropin releasing hormone (TRH) or its analogue RX77368, caused the extensor response to double in size and the flexor reflex to increase to 1.5-1.7 times pre-drug controls. The opioid RX77368 had no effect on the naloxone-reversible inhibition of the gastrocnemius reflex which followed tetanic stimulation of the fine afferent fibres of the common peroneal or sural nerves. The cholecystokinin antagonist proglumide, which has been shown to enhance the actions of endogenous opioids in some species, had no effects on either reflex. It is possible that TRH acts as an excitatory neurotransmitter or modulator in the spinal cord of the rabbit opposing, but not blocking, the actions of endogenous opioids.

Animals↗