Biomedical subjects

T E Salt

Publications and source records attributed to T E Salt.

At least 73 records · Page 4Linked to original sources

PubMed1992

Widely distributed GABA-mediated afferent inhibition processes within the ventrobasal thalamus of rat and their possible relevance to pathological pain states and somatotopic plasticity.

We have recently described extensive inhibitory interactions between inputs to the ventroposterolateral (VPL) (Roberts and Wells 1990, 1991) and ventroposteromedial (VPM) (Salt 1989) portions of the ventrobasal nucleus of the thalamus (VB). We wished to determine whether (i) the inhibition observed in the VPL was operating at the thalamic level, (ii) was dependent on GABA receptors, (iii) was demonstrable on neurons of the ventro-posteromedial nucleus of the thalamus (VPM) and (iv) was operant on test responses evoked by natural stimuli. Conditioning stimulation of sciatic nerve afferents caused inhibition of air jet evoked test responses of single VB neurons in urethane-anaesthetized rats. Both VPM and VPL neurons were subject to inhibition by conditioning stimulation of hindlimb afferents, indicating the wide-spread nature of the inhibitory process. This inhibition was reduced by the iontophoretic application of SR95531, a GABAA receptor antagonist. We conclude that there is a widely distributed inhibitory system operating in the somatic thalamus which involves both the medial and lateral portions of the nucleus and is, at least in part, mediated by GABAA receptors. The possible involvement of inhibitory processes and intrinsic membrane properties of thalamic neurones in the somatotopic plasticity of the sensory thalamus following deafferentation and in deafferentation pain is discussed.

Animals↗

PubMed1991

Excitatory amino acid receptors mediate synaptic responses to visual stimuli in superior colliculus neurones of the rat.

Excitatory amino acid receptors are involved in synaptic transmission throughout the central nervous system. As the specific synaptic pharmacology of visually responsive superior colliculus (SC) neurones has not been evaluated, we have attempted to antagonize visual responses of these neurones with selective excitatory amino acid antagonists. The N-methyl-D-aspartate (NMDA) receptor antagonist 3-((+/-)-2-carboxypiperazin-4-yl)propyl-1-phosphonic acid (CPP), and the non-NMDA receptor antagonist 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX) were applied iontophoretically in the vicinity of single visually responsive SC neurones. Visually evoked responses were antagonized by non-NMDA receptor selective currents of CNQX in 13 of 14 cells studied. Of 18 cells studied with NMDA receptor selective currents of CPP, visual responses were antagonized in only two cases. This study demonstrates that excitatory amino acid receptors are involved in synaptic transmission of visual information to the rat superior colliculus, but that NMDA receptors may play a relatively minor role.

6-Cyano-7-nitroquinoxaline-2,3-dione↗

PubMed1991

Membrane and action potential responses evoked by excitatory amino acids acting at N-methyl-D-aspartate receptors and non-N-methyl-D-aspartate receptors in the rat thalamus in vivo.

The membrane potential responses and firing patterns of rat thalamic neurons evoked by iontophoretically applied excitatory amino acids were recorded in vivo. All excitatory amino acids, including N-methyl-D,L-aspartate, evoked a membrane depolarization and a repetitive, regular pattern of action potential firing in the thalamus. Both non-nociceptive and nociceptive thalamic neurons responded to all agonists tested. Iontophoretic application of magnesium ions selectively antagonized responses to N-methyl-D,L-aspartate but did not convert the repetitive firing pattern into a burst firing pattern. In contrast, in the hippocampus, N-methyl-D,L-aspartate evoked a burst pattern of action potential firing associated with rhythmic depolarizing membrane potential shifts, similar to those seen by other workers in the hippocampus and in other brain regions. These findings are discussed in relation to the possibility that the regular firing pattern of spikes evoked by excitatory amino acids in the thalamus is primarily determined by the intrinsic membrane properties of thalamic neurons.

Action Potentials↗

PubMed1991

Non-competitive NMDA-receptor antagonists and anoxic degeneration of the ERG B-wave in vitro.

Studies have been undertaken to see if the non-competitive NMDA antagonists, ketamine, MK-801 and dextromethorphan would preserve the b-wave of the electroretinogram (ERG) in vitro. The drugs had no effect on the ERG b-wave, nor prolonged its survival postmortem. The present results support previous evidence suggesting that NMDA-receptors are not involved directly in synaptic transmission between photoreceptors and ON-bipolar cells. Further, loss of the b-wave in post-mortem anoxia does not appear to be mediated via NMDA-receptors.

Animals↗

PubMed1990

Postsynaptic potentials evoked in ventrobasal thalamus neurones by natural sensory stimuli.

Intracellular recordings were made in the ventrobasal thalamus of rats anaesthetised with urethane. Postsynaptic responses were evoked by stimulation of the peripheral receptive field with an air jet of 10 ms duration. The postsynaptic response typically consisted of an excitatory postsynaptic potential (EPSP)/inhibitory postsynaptic potential (IPSP) sequence with one or more evoked action potentials. Injection of hyperpolarizing current pulses appeared to increase the EPSP amplitude, whereas depolarising current pulses caused a reduction in EPSP amplitude. These changes in EPSP amplitude were however obscured by the presence of IPSPs and a slow potential similar to a low-threshold Ca2+ spike (LTS).

Animals↗

PubMed1990

Thalamic NMDA receptors and nociceptive sensory synaptic transmission.

The responses of single thalamic neurones to noxious thermal stimulation were recorded in anaesthetized rats. The selective N-methyl-D-aspartate (NMDA) receptor antagonist, 3-((+-)-2-carboxypiperazin-4-yl)propyl-l-phosphonate (CPP), antagonised nociceptive responses when ejected iontophoretically with currents which produced selective antagonism at NMDA receptors. In contrast, the non-NMDA excitatory amino acid receptor antagonist 6-cyano-7-nitroquinoxaline-2,3-dione (CNOX) had little or no effect on nociceptive responses, although it was able to reduce responses to non-nociceptive mechanoreceptor input. These results show that there is substantial NMDA receptor involvement in thalamic nociceptive responses, and that the contribution of CNQX-sensitive non-NMDA receptors to these responses is not extensive. Furthermore, it appears that nociceptive and non-nociceptive input to the thalamus have distinct synaptic pharmacologies.

6-Cyano-7-nitroquinoxaline-2,3-dione↗

PubMed1990

The contribution of the non-N-methyl-D-aspartate group of excitatory amino acid receptors to retinogeniculate transmission in the cat.

The N-methyl-D-aspartate receptor antagonist 3-((+/-)-2-carboxypiperazin-4-yl)-propyl-1-phosphonic acid and the non-N-methyl-D-aspartate receptor antagonist, 6-cyano-7-nitroquinoxaline-2,3-dione have been iontophoretically applied to cells in the cat dorsal lateral geniculate nucleus and their effects on the visual response compared. The objective was to examine the possibility of both N-methyl-D-aspartate and non-N-methyl-D-aspartate receptors being involved in the transfer of the retinal input to X and Y cells in the dorsal lateral geniculate nucleus. The results show that selective blockade of either N-methyl-D-aspartate receptors or non-N-methyl-D-aspartate receptors can block the visual response of both X and Y cells. Overall, the most potent reductions of visual responses across the population of cells studied were obtained with the N-methyl-D-aspartate receptor antagonist with X cells showing a slightly greater reduction on average (80%) than Y cells (66%). The relatively smaller overall reductions in visual responses obtained with the non-N-methyl-D-aspartate receptor blockade reflected the lower levels of blockade that were compatible with selectivity using iontophoretic applications of 6-cyano-7-nitroquinoxaline-2,3-dione. It is concluded that N-methyl-D-aspartate and non-N-methyl-D-aspartate receptors are critically involved in the visual response of both "on" and "off" centre X and Y cells.

6-Cyano-7-nitroquinoxaline-2,3-dione↗

PubMed1990

Sensory responses of caudal trigeminal neurons to thermal and mechanical stimuli and their behavioural correlates in the rat.

Behavioural experiments in the freely moving rat were carried out to determine thermal and mechanical nociceptive thresholds to ramp stimuli applied to the face. The mean thermal escape threshold was 43.5 degrees C, and the mean mechanical escape threshold was 179.2 g/mm2. In a parallel set of experiments recordings were made from single neurons in the caudal trigeminal nucleus of the anaesthetized rat. Neurons were classified according to their responses to a range of thermal and mechanical stimuli applied to the face. Three classes of neuron responded exclusively to mechanical stimuli and four classes responded to thermal stimuli (usually in addition to responding to mechanical stimuli). The mean thermal threshold of neurons responsive to warming stimulation was 44.4 degrees C. Neurons responsive to innocuous warming were located in deeper laminae. Many of the neurons responsive to noxious heat appeared to show an exponential relation between temperature and firing rate. An argument is made for a direct role of exponentially responding neurons in thermal nociception. The distribution of all neuronal response thresholds was left-skewed compared with a normal distribution, whereas the behavioural escape thresholds approximated a normal distribution.

Anesthesia↗

PubMed1990

Dependence of retinogeniculate transmission in cat on NMDA receptors.

1. We have examined the possibility that N-methyl-D-aspartate (NMDA) receptors may be involved in the visual response of relay cells in the cat dorsal lateral geniculate nucleus (dLGN). The selective NMDA receptor antagonists D-2-amino-5-phosphonovalerate (APV) and 3-[(+/-)-2-carboxypiperazin-4-yl]-propyl-1-phosphonic acid (CPP) have been iontophoretically applied to X and Y cells in the dLGN and their effects on the visual response to a light spot flashed within the receptive field center determined. 2. The antagonist effects were assessed at ejection current levels producing a selective blockade of the responses to iontophoretically applied NMDA with respect to those elicited by the non-NMDA receptor agonists quisqualate and kainate. These selective effects were determined in an experimental paradigm where the visual response and responses to NMDA and the non-NMDA receptor agonists were compared in the same test run. The data refer to a total population of 52 cells (28 X, 24 Y). 3. Application of APV abolished or greatly reduced the visual responses of both X and Y cells. The mean percentage reduction in the visual response for the X cells studied was 59 +/- 10% (SE; n = 7) and for the Y cells 66 +/- 8% (SE; n = 11). Both the early onset transient and the sustained component of the visual response to the flashed stimulus were equally affected. 4. The antagonist CPP produced a similar pattern of effect to APV, substantially reducing or abolishing the visual response in both X and Y cells.(ABSTRACT TRUNCATED AT 250 WORDS)

2-Amino-5-phosphonovalerate↗

PubMed1989

Modulation of NMDA receptor-mediated responses by glycine and D-serine in the rat thalamus in vivo.

The effects of iontophoretically applied glycine and D-serine upon responses of rat ventrobasal thalamus neurones to excitatory amino acids and sensory stimulation were investigated. Glycine inhibited excitatory responses to kainate, quisqualate and N-methyl-aspartate (NMA). Strychnine antagonised inhibitory responses to glycine, but in only a small number (2/7) of cases did such an antagonism reveal a facilitatory action of glycine on NMA responses. D-Serine inhibited responses of almost all neurones to either kainate or quisqualate, but enhanced responses to NMA on nearly half of the tested neurones, whilst having a weaker inhibitory action on the remainder. It is thus possible that D-serine has a dual action: (i) a facilitation of N-methyl-D-aspartate (NMDA) receptor-mediated responses and (ii) a non-selective inhibitory action.

Action Potentials↗

PubMed1989

Function of non-NMDA receptors and NMDA receptors in synaptic responses to natural somatosensory stimulation in the ventrobasal thalamus.

Sensory synaptic responses of rat ventrobasal thalamus neurones were challenged with iontophoretic applications of the excitatory amino acid antagonists CNQX and CPP. CNQX, applied with currents which were selective for non-NMDA receptors, antagonised responses of VB neurones to both 10 ms and 2000 ms air jet stimulation of the peripheral receptive field. In contrast, CPP only antagonised the latter type of response. These results suggest a differential involvement of excitatory amino acid receptors in sensory synaptic transmission to the ventrobasal thalamus, with an initial synaptic component being mediated by non-NMDA receptors (including kainate receptors), and a further NMDA receptor-mediated component being manifested upon maintained sensory stimulation. The expression of this latter component appears to be largely dependent upon the integrity of the non-NMDA receptor-mediated component.

6-Cyano-7-nitroquinoxaline-2,3-dione↗

PubMed1989

Modulatory effects of serotonin on excitatory amino acid responses and sensory synaptic transmission in the ventrobasal thalamus.

Excitatory amino acid receptors are thought to mediate sensory input to the ventrobasal thalamus. There is evidence for a brainstem serotonergic projection to the ventrobasal thalamus which may have a modulatory role. The possibility that serotonin may selectively modulate responses to excitatory amino acid receptor agonists, and its effects on sensory synaptic transmission has been examined in the rat ventrobasal thalamus in vivo. Iontophoretic ejection of serotonin at low currents produced a marked facilitation of responses to excitatory amino acids. In contrast, excitatory responses to cholinomimetic agonists were attenuated. Synaptic transmission was concomitantly enhanced or unchanged in these circumstances. Higher serotonin ejection currents reversed the facilitation, or inhibited excitatory amino acid responses and synaptic transmission. It is concluded that serotonin can modulate responses to excitatory amino acids relatively selectively and that synaptic transmission of somatosensory information through the ventrobasal thalamus may be susceptible to brainstem serotonergic modulation.

Action Potentials↗

PubMed1989

Gamma-aminobutyric acid and afferent inhibition in the cat and rat ventrobasal thalamus.

Extracellular single neuron recordings were made in the ventrobasal thalami of anaesthetized rats and cats. Physiological stimulation of vibrissa and hair follicle afferents was performed with an air jet (10-20 ms duration) directed at a single vibrissa or small area of hairy skin. Paired conditioning and test air jets delivered to the excitatory portion of receptive fields revealed inhibition of the response of ventrobasal thalamic neurons to test stimuli following the excitatory response to the conditioning stimulus. Such inhibitions could last up to 500 ms. An increase in neuronal excitability was sometimes observed following this inhibitory period. In addition, it was possible to produce inhibition without an excitatory response using conditioning stimuli delivered adjacent to the excitatory receptive field. Iontophoretic application of bicuculline methochloride, with currents that were adequate to antagonize iontophoretically applied GABA, was found to reduce the inhibition of test responses evoked by conditioning stimuli in almost all of the neurons studied. In most cases, no excitatory responses to conditioning stimuli directed outside the original excitatory receptive field were revealed by application of the GABA antagonist. In rats, bicuculline also led to a decrease in the post-inhibitory excitation, whereas in cats the converse appeared to be the case. These results suggest that GABAergic transmission may underlie inhibitory responses of cat and rat ventrobasal thalamus neurons to physiological stimulation of somatosensory afferents. Furthermore, removal of such inhibition does not appear to reveal excitatory inputs from outside of the original excitatory receptive field.

Acetylcholine↗

PubMed1988

The effects of N-acetylaspartylglutamate and distribution of N-acetylaspartylglutamate-like immunoreactivity in the rat somatosensory thalamus.

The ventrobasal thalamus and adjacent regions were stained for the presence of N-acetylaspartylglutamate-like immunoreactivity. Immunoreactive axonal terminals were observed in this area and also in certain non-specific thalamic nuclei, the reticular thalamic nucleus and the lateral geniculate nucleus. Stained somata were found in the habenula, centrolateral thalamic nucleus and reticular thalamic nucleus. Iontophoretically applied N-acetylaspartylglutamate had variable, although predominantly inhibitory, actions on ventrobasal thalamus neurons. These results indicate that N-acetylaspartylglutamate is unlikely to be the neurotransmitter of ascending somatosensory afferents, but do not rule out the possibility that it has some other neurotransmitter or neuromodulator role in the ventrobasal thalamus.

Action Potentials↗

PubMed1988

Antagonism of N-methylaspartate and synaptic responses of neurones in the rat ventrobasal thalamus by ketamine and MK-801.

1. Extracellular single neurone recordings were made in the ventrobasal thalamus of urethane-anaesthetized rats. 2. Iontophoretically and intravenously administered ketamine and MK-801 were found to be selective antagonists of responses of neurones to iontophoretically applied N-methylaspartate. 3. Both antagonists, administered in N-methylaspartate-selective quantities, reduced the synaptic responses of ventrobasal thalamus neurones to a two-second air jet directed at the peripheral receptive field.

Animals↗

PubMed1987

Excitatory amino acid receptors and synaptic transmission in the rat ventrobasal thalamus.

1. Extracellular single-neurone recordings were made in the ventrobasal thalamus (v.b.t.) of urethane-anaesthetized rats with multi-barrel ionophoretic electrodes in order to test the hypothesis that excitatory amino acid receptors are involved in the responses of these neurones to stimulation of sensory afferents. 2. Responses of neurones to either physiological stimulation of hair and vibrissa follicle sensory afferents and to ionophoretically applied excitatory amino acids were challenged with the antagonists D-2-amino-5-phosphonovalerate (APV), kynurenate and gamma-D-glutamylaminomethyl sulphonate (GAMS). 3. In agreement with previous findings in other brain areas, ionophoretically applied APV was found to selectively antagonize responses of v.b.t. neurones to N-methylaspartate (NMA), whereas GAMS was found to be moderately kainate selective. Kynurenate was found to be relatively non-selective. 4. Responses of neurones to short-duration (10-20 ms) physiological stimulation of afferents were resistant to APV when this antagonist was applied with NMA-selective ionophoretic currents. In contrast, these APV currents were adequate to antagonize responses to maintained physiological stimulation. 5. The broad spectrum excitatory amino acid antagonist kynurenate was found to block synaptic responses of v.b.t. neurones to both short-duration and maintained stimuli when it was applied with currents which were sufficient to reduce responses to ionophoretic quisqualate. 6. GAMS was found to selectively block kainate responses in a proportion of the neurones tested. In such cases, there was little effect of the antagonist on the responses evoked by either short-duration or maintained sensory stimuli. 7. It is concluded that excitatory amino acid receptors of both the NMDA and non-NMDA type are involved in the synaptic responses of v.b.t. neurones to sensory afferent stimulation, and that the apparent synaptic pharmacology depends on the mode of stimulation of the afferent pathway.

2-Amino-5-phosphonovalerate↗

PubMed1985

Modulatory and inhibitory processes in the visual cortex.

The functional role of three putative neurotransmitter systems in the visual cortex is compared; the GABAergic inhibitory interneurons, the interneurones containing somatostatin and the cholinergic input originating from the nucleus basalis of Meynert (nbM). Evidence is presented to support the role of GABAergic processes in the generation of the functional structure of the visual cortex and the view that the cholinergic input exerts a neuromodulatory influence enhancing stimulus selective responses. Although the neuropeptide somatostatin produces facilitatory and inhibitory effects on visual cortical cells there is no clear functional pattern to its action. The possible significance of this data and the interaction of SSt with GABA is discussed in the light of evidence that they may coexist in some cells.

Acetylcholine↗

PubMed1983

Distribution of substance P-responsive and nociceptive neurones in relation to substance P-immunoreactivity within the caudal trigeminal nucleus of the rat.

Substance P is a peptide which is found in small diameter primary afferent fibres and may have a function in nociceptive afferent transmission. In order to study the role of substance P in sensory processes in depth, we have compared the distributions of nociceptive neurones and substance P-responsive neurones with the distribution of substance P in the caudal trigeminal nucleus of the rat. It was found that substance P-like immunoreactivity was located primarily in the superficial layers of nucleus caudalis (equivalent to laminae I and II of the dorsal horn) and in more ventromedially located areas (equivalent to laminae V and VI). The distribution was found to be in good agreement with the distribution of nociceptive neurones. Iontophoretically applied substance P had predominantly excitatory actions on both nociceptive and non-nociceptive nucleus caudalis neurones, although the peptide did appear to be slightly more likely to excite nociceptive neurones. Similarly, the peptide appeared slightly more likely to be excitatory in areas of nucleus caudalis showing substance P staining, but excitations were also predominantly seen in areas containing little or no apparent substance P staining. These results are consistent with the proposed role for substance P as a nociceptive afferent neurotransmitter. However, it is also possible that the peptide performs other functions in the processing of sensory information.

Animals↗