Responses of rostral hypothalamic neurones to peripheral temperature and to amines

1. Five-barrelled micropipettes have been used to record extracellularly the activity of neurones in the rostro-medial hypothalamus of methoxyflurane-anaesthetized cats, and to apply acetylcholine (ACh), noradrenaline (NA) and 5-hydroxytryptamine (5-HT) by micro-iontophoresis to the vicinity of each neurone encountered. Peripheral thermal stimulation was achieved by blowing warm (42 degrees C) and cold (4 degrees C) air in the face of the animal, and thermoresponsiveness was compared with amine responsiveness.2. One hundred and twenty-two neurones were obtained from ten cats. Eleven (9%) were warm-responsive and sixteen (13%) were cold-responsive. The rest did not respond to facial warming or cooling.3. No consistent relationship was observed between amine responses and responsiveness to facial temperature. Warm-responsive neurones were mainly depressed or unaffected by amines. Cool-responsive neurones were excited, depressed or unaffected by amines with the exception that no 5-HT excitations were seen. Thermoresponsive neurones were more likely to be amine depressed than non-thermoresponsive neurones.4. Six thermoresponsive neurones responded to peripheral temperature and to amines in a way which fitted the amine model of Myers (1971). Fifteen thermoresponsive neurones fitted the model of Bligh, Cottle & Maskrey (1971), according to the same criteria.5. The results lend little support to the amine model, as predicted from amine micro-injection and release studies in primates, but support more strongly the model of Bligh et al. (1971) which is based on intraventricular injections of amines in sheep, goats and rabbits. On the basis of the latter model, functional identification was possible in 63% of the thermoresponsive rostral hypothalamic neurones tested.     

Encoding of electrical, thermal, and mechanical noxious stimuli by subnucleus reticularis dorsalis neurons in the rat medulla

1. In anesthetized rats, recordings were made within the medullary subnucleus reticularis dorsalis (SRD) from neurons that exhibited convergence of nociceptive inputs from the entire body. Neurons with total nociceptive convergence (TNC) responded to suprathreshold percutaneous electrical stimuli (2-ms duration) with an early and a late peak due to activation of A delta- and C-fibers, respectively, no matter which part of the body was stimulated. Neurons with partial nociceptive convergence (PNC) responded to the same stimuli with an A delta-peak regardless of which part of the body was stimulated and with a C-peak of activation from some, mainly contralateral, parts of the body. The characteristics of the responses of these neurons to the application of graded intensities of electrical, thermal, and mechanical stimuli were analyzed. 2. All TNC neurons and 85% of PNC neurons responded to A delta- and C-fiber activation following percutaneous electrical stimulation of the contralateral hindpaw. With regard to A delta-fiber-evoked responses, a linear relationship between the logarithm of the applied current and the magnitude of the responses was found within the 0.25- to 6.0-mA and 0.5- to 24-mA ranges for TNC and PNC neurons, respectively; however, these curves were essentially similar. With regard to C-fiber-evoked responses, such a linear relationship was found within the 1.5- to 6.0-mA range for both types of SRD neurons, although the TNC neurons presented larger C-fiber-evoked responses than did the PNC neurons. 3. TNC and PNC neurons linearly increased their discharges during the application of noxious thermal stimuli to the contralateral hindpaw within the range 44-52 degrees C; the mean responses evoked by noxious heat from TNC neurons were of higher magnitude than those from PNC neurons. The majority of SRD neurons presented long-lasting afterdischarges, especially with the highest temperature employed (52 degrees C). 4. TNC neurons monotonically increased their discharges during graded mechanical or thermal stimulation of the tail. When mechanical stimuli were applied, a linear relationship was found between the logarithm of the strength of the mechanical stimulus and the neuronal discharges, in the 5.3- to 7.4-N/cm2 range. With thermal stimulation, TNC neurons linearly increased their discharges in the 44-52 degrees C range. When increasing amounts of the tail were immersed in a 50 degrees C waterbath, TNC neurons increased their discharges within a restricted range of tail surface areas (0.9-5.7 cm2); further increases in the stimulated surface size were not followed by increases in firing rate.(ABSTRACT TRUNCATED AT 400 WORDS)     

The dynamic properties of trigeminal thermoreceptors following heat-rearing in rats

Summary Dynamic properties of thermoresponsive units at the caudal trigeminal nucleus are not modified by heat-rearing. The modification of the thermoregulatory system by heat-rearing is unlikely to be a consequence of altered thermoreceptive function at this level.Rats were reared at ambient temperatures of 30°C (heat-reared) and 20°C (controls). Extracellular recordings of thermoresponsive units at the caudal trigeminal nucleus were made while the facial receptive fields of these thermoresponsive units were stimulated with 6 different rates of temperature change (+0.5, +0.1, +0.02, –0.02, –0.1 and –0.5°C/sec). All thermoresponsive units encountered were cold-sensitive. The static maxima were clustered around 13.5°C and did not differ between treatment groups. Dynamic maxima occurred at temperatures around 29–30°C and were not different in thermoresponsive neurones from the two treatment groups. There was no difference between the two treatment groups in the dynamic activity of trigeminal cold-responsive neurones at any of the 42 combinations of temperature and rate of temperature change examined.     

Enhanced responses of spinal dorsal horn neurons to heat and cold stimuli following mild freeze injury to the skin

The effects of a mild freeze injury to the skin on responses of nociceptive dorsal horn neurons to cold and heat stimuli were examined in anesthetized rats. Electrophysiological recordings were obtained from 72 nociceptive spinal neurons located in the superficial and deep dorsal horn. All neurons had receptive fields (RFs) on the glabrous skin of the hindpaw, and neurons were functionally divided into wide dynamic range (WDR) and high-threshold (HT) neurons. Forty-four neurons (61%) were classified as WDR and responded to both innocuous and noxious mechanical stimuli (mean mechanical threshold of 12.8 +/- 1.6 mN). Twenty-eight neurons (39%) were classified as HT and were excited only by noxious mechanical stimuli (mean mechanical threshold of 154.2 +/- 18.3 mN). Neurons were characterized for their sensitivity heat (35 to 51 degrees C) and cold (28 to -12 degrees C) stimuli applied to their RF. Among WDR neurons, 86% were excited by both noxious heat and cold stimuli, while 14% responded only to heat. For HT neurons, 61% responded to heat and cold stimuli, 32% responded only to noxious heat, and 7% responded only to noxious cold. Effects of a mild freeze injury (-15 degrees C applied to the RF for 20 s) on responses to heat and cold stimuli were examined in 30 WDR and 22 HT neurons. Skin freezing was verified as an abrupt increase in skin temperature at the site of injury due to the exothermic reaction associated with crystallization. Freezing produced a decrease in response thresholds to heat and cold stimuli in most WDR and HT neurons. WDR and HT neurons exhibited a mean decrease in response threshold for cold of 9.0 +/- 1.3 degrees C and 10.0 +/- 1.6 degrees C, respectively. Mean response thresholds for heat decreased 4.0 +/- 0.4 degrees C and 4.3 +/- 1.3 degrees C in WDR and HT neurons, respectively. In addition, responses to suprathreshold cold and heat stimuli increased. WDR and HT neurons exhibited an 89% and a 192% increase in response across all cold stimuli, and a 93 and 92% increase in responses evoked across all heat stimuli, respectively. Our results demonstrate that many spinal neurons encode intensity of noxious cold as well as noxious heat over a broad range of stimulus temperatures. Enhanced responses of WDR and HT neurons to cold and heat stimuli after a mild freeze injury is likely to contribute to thermal hyperalgesia following a similar freeze injury in humans.     

Raphe magnus/pallidus neurons regulate tail but not mesenteric arterial blood flow in rats

In urethane-anesthetized rats with body temperature maintained at 39-40 degrees C, electrical stimulation of raphe magnus/pallidus/parapyramidal region within 0.5 mm of the ventral medullary surface reduced arterial blood flow to the tail cutaneous bed (measured with a chronically implanted Doppler ultrasonic flowmeter) from 28+/-5 to 6+/-1 cm/s (P<0.01), without changing mesenteric arterial blood flow, and with only small, variable changes in arterial pressure. Injection of bicuculline (50 pmol in 50 nl) at the same site reduced tail flow from 19+/-2 to 3+/-1 cm/s (P<0.01), again without significantly changing mesenteric flow, but with a moderate increase in arterial pressure. When the rat was cooled to reduce basal tail blood flow, injection of muscimol (1 nmol in 100 nl) or GABA (100 nmol in 100 nl) into the raphe site restored tail blood flow to 93+/-4% of the pre-cooling level.These recordings are the first reported direct measurements of rat tail blood flow changes elicited by alteration of neuronal function in the brainstem. The rostral medullary raphe controls the tail cutaneous vascular bed in a relatively selective manner. Our findings add to evidence that raphe magnus/pallidus/parapyramidal neurons are involved in regulating cutaneous blood flow in response to changes in body temperature in the rat.     

Convergence of heterotopic nociceptive information onto neurons of caudal medullary reticular formation in monkey (Macaca fascicularis)

1. Recordings were made in anesthetized monkeys from neurons in the medullary reticular formation (MRF) caudal to the obex. Responses of 19 MRF neurons to mechanical, thermal, and/or electrical stimulation were examined. MRF neurons exhibited convergence of nociceptive cutaneous inputs from widespread areas of the body and face. 2. MRF neurons exhibited low levels of background activity. Background activity increased after periods of intense cutaneous mechanical or thermal stimulation. Nearly all MRF neurons tested failed to respond to heterosensory stimuli (flashes, whistle sounds), and none responded to joint movements. 3. MRF neurons were excited by and encoded the intensity of noxious mechanical stimulation. Responses to stimuli on contralateral limbs were greater than those to stimuli on ipsilateral limbs. Responses were greater to stimuli on the forelimbs than to stimuli on the hindlimbs. 4. MRF neurons responded to noxious thermal stimulation (51 degrees C) of widespread areas of the body. Mean responses from stimulation at different locations were generally parallel to those for noxious mechanical stimulation. Responses increased with intensity of noxious thermal stimulation (45-50 degrees C). 5. MRF neurons responded with one or two peaks of activation to percutaneous electrical stimulation applied to the limbs, the face, or the tail. The differences in latency of responses to stimulating two locations along the tail suggested that activity was elicited by activation of peripheral fibers with a mean conduction velocity in the A delta range. Stimulation of the contralateral hindlimb elicited greater responses, with lower thresholds and shorter latencies, than did stimulation of the ipsilateral hindlimb. 6. Electrophysiological properties of monkey MRF neurons resembled those of neurons in the medullary subnucleus reticularis dorsalis (SRD) in the rat. Neurons in the caudal medullary reticular formation could play a role in processing nociceptive information. Convergence of nociceptive cutaneous input from widespread areas of the body suggests that MRF neurons may contribute to autonomic, affective, attentional, and/or sensory-motor processes related to pain.     

Single-unit responses of serotonergic medullary and pontine raphe neurons to environmental cooling in freely moving cats

Brain serotonin has long been implicated in the regulation of body temperature, although its precise role is not completely understood. The present study examined the effects of environmental cooling (4-8 degrees C for 2 or 4h) on the single-unit activity of serotonergic neurons recorded in the medullary raphe nuclei obscurus and pallidus and in the pontine dorsal raphe nucleus of freely moving cats. These neuronal groups have primarily descending projections to the spinal cord and ascending projections to the forebrain, respectively. Cold exposure induced shivering and piloerection, but no appreciable changes in core temperature. Of the medullary serotonergic cells studied (n=14), seven were activated and seven were unresponsive to cold exposure. For the responsive cells, the mean increase and peak effect in unit activity relative to baseline were 31% and 46%, respectively. Of the seven cold-responsive cells, the activity of four was monitored when the animals were transferred back to room temperature (23 degrees C). Within 15-30 min, the activity of these cells returned to baseline. In contrast, none of the dorsal raphe nucleus cells studied (n=14) displayed a significant change in neuronal activity during cold exposure, suggesting that these neurons do not receive afferent input from cold-sensitive cutaneous receptors or participate in thermoregulatory responses evoked by low ambient temperatures.Overall, these results suggest that a subset of medullary serotonergic neurons play a role in physiological mechanisms underlying cold defense (e.g. increases in motor output and/or autonomic outflow). On the other hand, the lack of responsiveness of serotonergic dorsal raphe nucleus neurons to cold exposure does not support a specific role for these cells in thermoregulation.     

Unit responses in the medulla oblongata of rabbit to changes in local and cutaneous temperature.

1. In anaesthetized rabbits which were stereotaxically implanted with a thermode following decerebellation, thermal sensitivity of neurones in the medulla oblongata to local temperature changes was examined systematically. The medullary temperature was changed by circulating water at various temperatures through the thermode. 2. Eighty-seven temperature-responsive neurones were found in the medulla, especially in the medullary reticular formation. Out of these eighty-seven, forty-eight neurones were cold-responsive neurones, while the rest were warm-responsive. Both types of neurones included not only neurones with linear or continuous relations between discharge rate and local temperature but also neurones with non-linear or discontinuous thermoresponse curves. 3. In the medulla a few of the temperature-responsive neurones showed a dynamic reaction with static discharge rate changes to changes of local temperature. 4. Seven neurones out of the fifteen respiratory neurones encountered during the exploration had thermal sensitivity to respiratory alteration of the discharge. 5. with thermal stimulation of a limited area of the skin, over 50% of the temperature-responsive neurones recorded in the medulla responded positively or negatively to changes in the skin temperature.     

Responses of medullary raphespinal neurons to electrical stimulation of thoracic sympathetic afferents, vagal afferents, and to other sensory inputs in cats.

1. Medullary raphespinal neurons antidromically activated from the T2-T5 segments were tested for responses to electrical stimulation of cervical vagal and thoracic sympathetic afferents (by stimulating the left stellate ganglion), somatic probing, auditory stimuli, and visual stimuli in cats anesthetized with alpha-chloralose. A total of 99 neurons in the raphe nuclei were studied; the locations of 76 cells were histologically confirmed. Neurons were located in raphe magnus (RM, 65%), raphe obscurus (RO, 32%), and raphe pallidus (RPa, 4%). The mean conduction velocity of these neurons was 62 +/- 2.9 (SE) m/s with a range of 1.1-121 m/s. 2. A total of 60/99 tested neurons responded to electrical stimulation of sympathetic afferents. Quantitation of responses was obtained for 55 neurons. With one exception, all responsive neurons were excited and exhibited an early burst of spikes with a mean latency of 16 +/- 1.2 ms. From a spontaneous discharge rate of 5.2 +/- 1.2 spikes/s, neuronal activity increased by 2.9 +/- 0.3 spikes/stimulus. In addition to an early peak, 15 neurons (25%) exhibited a late burst of spikes with a latency of 182 +/- 12.9 ms; neuronal activity increased by 5.0 +/- 1.3 spikes/stimulus. Duration of the late peak (130 +/- 18.5 ms) was longer than for the early peak (18 +/- 0.7 ms), but threshold voltages for eliciting each peak were comparable. Sixteen of 29 spontaneously active neurons exhibited a postexcitatory depression of activity that lasted for 163 +/- 19.1 ms. All but one tested neuron in RO responded to stimulation of sympathetic afferents, but 65% of neurons in RM responded to this stimulus. 3. In response to vagal afferent stimulation, 19% of 57 neurons exhibited inhibition only, 11% were only excited, and 9% were either excited or inhibited, depending on the stimulus paradigm used; the remaining 61% of neurons were unresponsive. From a spontaneous rate of 7.9 +/- 3.8 spikes/s, excited cells increased their discharge rate by 1.6 +/- 0.3 spikes/stimulus. Activity of inhibited cells was reduced from 21.3 +/- 5.8 to 7.8 +/- 3.1 spikes/s. The conditioning-test (CT) technique was used to assess 11 neurons' responses. Stellate ganglion stimulation was the test stimulus, and vagal stimulation the conditioning stimulus. Vagal stimulation reduced the neuronal responses to stellate ganglion stimulation by an average of 50% with a CT interval of 60-100 ms, and cell responses returned to control after 300 ms. With spontaneous cell activity, low frequencies of vagal stimulation were generally excitatory, and high frequencies (10-20 Hz) inhibitory.(ABSTRACT TRUNCATED AT 400 WORDS)     

Characteristics, specificity, and efferent control of frog cutaneous cold receptors

1. Thermal stimulation of frog skin produces a discharge in afferents in the dorsocutaneous nerve. The characteristics of this response have been examined with regard to static and dynamic sensitivity to thermal stimuli and to mechanical sensitivity. Frog cutaneous receptors respond only to cooling, with no response to warming through the same thermal range.2. The static temperature at which these receptors are maximally active is about 24 degrees C for Rana pipiens and about 27 degrees C for R. catesbiana.3. The dynamic sensitivity of frog cutaneous receptors is linearly related to both stimulus slope and magnitude. Maximum dynamic sensitivity was between -90 and -120 impulses/ degrees C.sec.4. Antidromic occlusion experiments demonstrate relative insensitivity of these receptors to tonic mechanical stimulation. At high stimulus intensities, however, larger fibres are recruited into the response; this recruitment of action potentials of larger amplitude is a linear function of both stimulus slope and magnitude.5. Spike heights are linearly related to conduction velocities in the dorsocutaneous nerve; tonic mechanoreceptors have a mean spike height of 28.4+/-0.6 muV and conduction velocities about 6-8 m/sec, whereas these temperature sensitive receptors have spike heights 15.8+/-0.4 muV and conduction velocities about 3-4 m/sec.6. Maximum dynamic sensitivity skin is increased following stimulation of the first or second sympathetic ganglion. This increase is both marked and progressive, reaching a maximal enhancement of about 150-160% control at a stimulus rate of 5 stimuli/train, each train delivered once every 5 sec.7. Static sensitivity of the cold receptors is also increased following sympathetic stimulation. This increased sensitivity is shown by both increased discharge rate within the same thermal range and by decreased temperature of maximum static sensitivity.8. Sympathetic modulation of dynamic thermal sensitivity is mimicked by epinephrine and norepinephrine in doses of 10(-6)-10(-7) g/ml. Ephedrine, another adrenergic agonist, also mimics the enhancement of cold receptors by sympathetic stimulation.9. Larger fibres are recruited to account for the increased sensitivity of thermoreceptors following sympathetic stimulation and epinephrine application.10. Propranolol and phentolamine both block the enhancement of the response by sympathetic stimulation, but propranolol blocks the response of the receptor to thermal stimulation as well. Reserpine pre-treatment blocks the effect of sympathetic stimulation on the cold response.     

Activation of the parapyramidal region in the ventral medulla stimulates gastric acid secretion through vagal pathways in rats

Neurons synthesizing thyrotropin-releasing hormone, substance P and serotonin in the medullary caudal raphe nuclei project to the dorsal vagal complex and play a role in the central vagal regulation of gastric function. Neurons in the parapyramidal region in the ventral medulla share similar biochemical coding and projections as those in the caudal raphe nuclei. The role of the parapyramidal region in the autonomic regulation of gastric acid secretion was investigated in urethane-anesthetized rats. Unilateral microinjection of kainate into the parapyramidal region at 10, 15 and 20 ng induced a dose-related stimulation of gastric acid secretion (net increases: 22.2+/-11.2, 40.5+/-8.5 and 89.8+/-19.4 micromol/60 min, respectively), while injection of vehicle had no effect (net change: -0.1+/-1.4 micromol/60 min). Time-course studies showed a nine-fold peak increase over basal at 30 min after parapyramidal injection of kainate (20 ng) and acid secretion returned to basal level at 70 min. Microinjections of kainate (15-20 ng) outside the parapyramidal region or into the parapyramidal region in vagotomized rats had no effect. Exposure to cold (4 degrees C) for 2 h, which is known to induce vagally mediated gastric secretory and motor responses through medullary thyrotropin-releasing hormone pathways, increased the number of Fos-positive cells in the caudal, middle and rostral parts of the parapyramidal region to 4.3+/-0.4, 9.4+/-0.9 and 18.4+/-1.6/section, respectively, compared with 0.1+/-0. 1, 0.1+/-0.0 and 0.7+/-0.6/section, respectively, in rats maintained at room temperature. Most of the Fos-labeled cells co-expressed pro-thyrotropin-releasing hormone messenger RNA signal and/or were serotonin immunoreactive. These data show that chemical activation of neurons in the parapyramidal region results in a vagal-dependent stimulation of gastric acid secretion and that acute cold exposure activates parapyramidal neurons containing pro-thyrotropin-releasing hormone and/or serotonin, suggesting a potential role of the parapyramidal region, in addition to the caudal raphe nuclei, as medullary sites involved in the vagal regulation of gastric function.     

Modulation of spinal nociceptive transmission from nuclei tractus solitarii: a relay for effects of vagal afferent stimulation

1. The effects of electrical and chemical stimulation in the nucleus tractus solitarii (NTS) on spinal nociceptive transmission were examined in pentobarbital sodium-anesthetized, paralyzed rats. These studies also examined the role of the NTS as a relay for the effects of vagal afferent stimulation (VAS) on spinal nociceptive transmission. All 75 neurons studied were located in laminae I-VI in the L3-L5 spinal segments, with receptive fields on the glabrous skin of the plantar surface of the ipsilateral hindpaw. The units responded to mechanical (low and/or high intensities) and thermal stimuli (42-52 degrees C). 2. Electrical stimulation in the NTS either ipsilateral or contralateral to the spinal unit inhibited neuronal responses to noxious thermal stimuli. The magnitude of inhibition did not significantly differ as a function of either ipsilateral (15 units) or contralateral (12 units) NTS stimulation (NTSS) as indicated by extrapolated thresholds for inhibition of responses to heat, intensities to produce 50% inhibition of responses to heat, and the slope of recruitment lines for inhibition. Tracking experiments also revealed that stimulation in the area ventral to the NTS produced a greater magnitude of inhibition of these units than did NTSS. 3. NTSS significantly decreased the slope of the stimulus-response functions (SRFs) of dorsal horn units to graded thermal stimuli (42-52 degrees C), whereas response threshold was unaffected by NTSS. The apparent latency of NTSS to produce inhibition of unit responses to heating of the hindpaw was determined to be 50 +/- 10 ms (mean +/- SE). 4. Microinjection of 50 nmol of glutamate into the NTS ipsilateral to the spinal unit also inhibited neuronal responses to thermal stimuli in 17/21 units; responses of 2/21 units were facilitated. Inhibition typically lasted 4-7 min and was shown to be dose-volume dependent. 5. The effects of VAS and NTSS on spinal nociceptive transmission were directly compared. The responses of 17 units to 50 degrees C heating of the hindpaw were facilitated by low and inhibited by greater intensities of VAS (Biphasic units); the responses of 12 units were only inhibited by VAS (Inhib units); three were only facilitated (Facil units), and 2 were unaffected by VAS. In contrast, NTSS generally inhibited the same spinal units, although modest facilitation was produced by NTSS contralateral to the recording site. NTSS produced greater inhibition of the Biphasic units than did VAS, shown by a leftward shift of the recruitment line of inhibition and greater inhibition at the same intensity of electrical stimulation.(ABSTRACT TRUNCATED AT 400 WORDS)     

Transient spinal cord ischemia induces temporary hypersensitivity of dorsal horn wide dynamic range neurons to myelinated, but not unmyelinated, fiber input.

1. The activity of 197 single dorsal horn neurons was recorded extracellularly in the spinal cord of decerebrate, spinalized, unanesthetized rats. The response properties of 174 wide dynamic range (WDR) neurons to electrical, mechanical, and thermal stimulation in three groups of rats were studied:normal, 1-4 days after transient spinal cord ischemia induced photochemically by laser irradiation when the rats exhibited behavioral hypersensitivity to mechanical stimuli (allodynia), and 10-20 days after spinal ischemia when the allodynia had ceased. 2. In normal rats, the responses of dorsal horn WDR neurons to suprathreshold electrical stimulation of their receptive fields consisted of a short-latency (A) and a long-latency (C) response. In 77% of the neurons (57/74), there was a separation between the A- and C-fiber responses. The response threshold (defined as 20% increase in neuronal discharges above background activity) to mechanical stimulation applied with calibrated von Frey hairs was 13.8 g, and the discharges of these neurons to graded stimulation increased linearly. 3. In 68% of WDR neurons in allodynic rats (38/56), the response to suprathreshold electrical stimuli was a single burst with no separation between A- and C-fiber responses. The magnitude and duration of the response were significantly increased compared with those recorded in normal rats. The sensitivity of these neurons to mechanical stimulation was also greatly increased, expressed by a lowered threshold (2.1 +/- 0.3 g, mean +/- SE) and a shift to the left of the nonlinear stimulus-response curve. The background activity of the neurons and the size of the receptive fields were, however, unchanged.(ABSTRACT TRUNCATED AT 250 WORDS)     

Responses to taste stimulation in the ventroposteromedial nucleus of the thalamus in rats

Extracellular action potentials were recorded from 73 neurons in the parvicellular division of the ventroposteromedial (VPMpc) nucleus of the thalamus of anesthetized Wistar rats during gustatory, thermal, and tactile stimulation of the whole oral cavity. The stimulus array consisted of 16 room-temperature (23 degrees C) sapid stimuli, distilled water at three temperatures (0, 23, and 37 degrees C), and 0.1 M NaCl at three temperatures (0, 23, and 37 degrees C). Among all 151 neurons isolated in VPMpc, 9% responded exclusively to taste, 33% to taste and temperature, none to taste and touch, but 6% to all three modalities. Discharge rates evoked by the basic tastants were 13.8 +/- 1.6 (SD) spikes/s for 0.1 M NaCl, 9.3 +/- 1.4 spikes/s for 0.01 M HCl, 5.1 +/- 0.9 spikes/s for 0.5 M sucrose, and 4.3 +/- 0.6 spikes/s for 0.01 M quinine HCl. Water evoked mean responses at 0, 23, and 37 degrees C of 9.9 +/- 1.5, 0.6 +/- 0.4, and 1.3 +/- 0.9 spikes/s, respectively. The mean firing rate evoked by 37 and 0 degrees C NaCl was 15.0 +/- 2.4 and 17.0 +/- 2.8 spikes/s, respectively. The exponent of the NaCl concentration-response power function was 0.39. Thalamic taste cells were broadly tuned. The mean breadth-of-tuning coefficient for these 73 gustatory cells was 0.79 +/- 0.02. Two cells responded predominantly with inhibition, which accounted for the majority of inhibitory responses. The taste neurons were statistically divisible into three groups: sodium-oriented (n = 40), acid-oriented (n = 12), and sugar-oriented (n = 17). Four additional bitter-oriented neurons were not closely enough related to be defined as a group and were considered outliers. The sodium-oriented group could be divided into three statistically distinct subgroups, differing in the specificity of their responses to NaCl. With respect to polymodal sensitivity, spontaneous rate, evoked response rates, signal-to-noise ratio, proportions of cells responding best to basic tastants, taste neuron groups, taste spaces, and temporal responses, VPMpc neurons have characteristics that are intermediate between those of parabrachial and cortical gustatory neurons.     

Quantitative characterization and spinal pathway mediating inhibition of spinal nociceptive transmission from the lateral reticular nucleus in the rat

1. The modulation of spinal nociceptive transmission from the lateral reticular nucleus (LRN) was characterized for 47 spinal dorsal horn neurons in pentobarbital-anesthetized, paralyzed rats. All 47 units studied had receptive fields confined to the glabrous skin of the plantar surface of the ipsilateral hind foot and responded to mechanical stimulation as well as noxious heating (50 degrees C). Rostral projections contained in the ventrolateral quadrant of the cervical spinal cord were demonstrated for 15 of the 47 units by antidromic invasion. Glutamate- and stimulation-produced descending inhibition, the spinal pathway, and tonic descending inhibition from the LRN were systematically examined. 2. Inhibition of unit responses to heating of the skin by electrical stimulation in the LRN varied with the intensity, pulse duration (100 or 400 microseconds), and frequency (25-100 Hz) of stimulation. Greater inhibition was produced at lower intensities of stimulation with the 400-microseconds pulse duration and a frequency of 100 Hz. The effects of stimulation on spontaneous activity and responses to heat were compared in 16 experiments; inhibition of spontaneous activity was intensity dependent and did not differ significantly in magnitude from stimulation-produced inhibition of responses to heating of the skin. 3. Tracking experiments established that stimulation in the ipsilateral and contralateral ventrolateral medulla reliably attenuated unit responses to noxious heating of the skin and that stimulation in the LRN produced maximal inhibition at a low intensity of stimulation. Descending inhibition was quantitatively characterized from sites within (n = 32) and outside (n = 30) the LRN. Both the extrapolated mean stimulation threshold for inhibition and mean intensity inhibiting unit responses to heat to 50% of control were significantly lower for sites in the LRN. 4. The responses of seven spinal units to graded noxious heating of the skin were studied; all exhibited linear monotonic stimulus-response functions (SRFs) throughout the temperature range examined (42-50 degrees C). Electrical stimulation in the LRN significantly decreased the slope (42 +/- 4% of control) of the SRFs and increased the neuronal response threshold (2.0 +/- 0.7 degrees C). 5. S-glutamate (50 nmol, 0.5 microliter) was microinjected into stimulation sites within (n = 15) and distant from (n = 6) the LRN. Glutamate produced a transient (less than 7 min) but significant attenuation of neuronal responses to heat to 35 +/- 6% of control only when microinjected into the LRN.(ABSTRACT TRUNCATED AT 400 WORDS)     

Responses of primate SI cortical neurons to noxious stimuli

Recordings were made from single SI cortical neurons in the anesthetized macaque monkey. Each isolated cortical neuron was tested for responses to a standard series of mechanical stimuli. The stimuli included brushing the skin, pressure, and pinch. The majority of cortical neurons responded with the greatest discharge frequency to brushing the receptive field, but neurons were found in areas 3b and 1 that responded maximally to pinching the receptive field. A total of 68 cortical nociceptive neurons were examined in 10 animals. Cortical neurons that responded maximally to pinching the skin were also tested for responses to graded noxious heat pulses (from 35 to 43, 45, 47, and 50 degrees C). If the neuron failed to respond or only responded to 50 degrees C, the receptive field was also heated to temperatures of 53 and 55 degrees C. Fifty-six of the total population of nociceptive neurons were tested for responses to the complete series of noxious heat pulses: 46 (80%) exhibited a progressive increase in the discharge frequency as a function of stimulus intensity, and the spontaneous activity of two (4%) was inhibited. One population of cortical nociceptive neurons possessed restricted, contralateral receptive fields. These cells encoded the intensity of noxious mechanical and thermal stimulation. Sensitization of primary afferent nociceptors was reflected in the responses of SI cortical nociceptive neurons when the ascending series of noxious thermal stimulation was repeated. The population of cortical nociceptive neurons with restricted receptive fields exhibited no adaptation in the response during noxious heat pulses of 47 and 50 degrees C. At higher temperatures the response often continued to increase during the stimulus. The other population of cortical nociceptive neurons was found to have restricted, low-threshold receptive fields on the contralateral hindlimb and, in addition, could be activated only by intense pinching or noxious thermal stimuli delivered on any portion of the body. The stimulus-response functions obtained from noxious thermal stimulation of the contralateral hindlimb were not different from cortical nociceptive neurons with small receptive fields. However, nociceptive neurons with large receptive fields exhibited a consistent adaptation during a noxious heat pulse of 47 and 50 degrees C. Based on the response characteristics of these two populations of cortical nociceptive neurons, we conclude that neurons with small receptive fields possess the ability to provide information about the localization, the intensity, and the temporal attributes of a noxious stimulus.4+.     

Inhibition of spinal nociceptive information by stimulation in midbrain of the cat is blocked by lidocaine microinjected in nucleus raphe magnus and medullary reticular formation

The organization in the brain stem of descending inhibitory control of spinal nociceptive information was studied in anesthetized, paralyzed cats by quantitatively evaluating the effects of reversible blocks produced by lidocaine microinjected in the medial and/or lateral medulla. Spinal neuronal inhibition produced by stimulation in the nucleus raphe magnus (NRMS) was compared to the inhibition of the same dorsal horn neurons produced by stimulation 2 mm lateral in the medullary reticular formation (MRFS). When the inhibition produced by NRMS and/or MRFS was blocked by lidocaine microinjected in those medullary sites, the efficacy of spinal neuronal inhibition produced by stimulation in the midbrain periaqueductal gray (PAGS) and 4 mm lateral in the reticular formation (LRFS) was evaluated and compared with the inhibition produced before the intramedullary microinjection of lidocaine. All 32 spinal dorsal horn neurons studied responded to hindlimb cutaneous nerve stimulation at strengths supramaximal for activation of A-alpha,delta- and C-fibers, to mechanical stimuli applied to the skin, and 27 also responded to noxious radiant heating (50 degrees C, 10 s) of the skin of the foot- or toepads (5 units had receptive fields in the hairy skin of the hindlimb). The noxious heat-evoked responses of all units studied were inhibited by NRMS or MRFS. The mean threshold currents for spinal inhibition, the mean maximal inhibition produced, and the mean stimulation currents producing an attenuation to 50% of the control response to 50 degrees C skin heating did not differ between NRMS and MRFS. When quantitatively compared on the same spinal units, NRMS produced the same mean magnitude of inhibition as the same intensities of MRFS, and both NRMS and MRFS produced the same mean percent increment in inhibition per 100-microA increase in the intensity of brain stimulation. The responses of the spinal units studied to graded noxious heating of the skin was a monotonic linear function throughout the temperature range employed (42-50 degrees C). MRFS shifted this stimulus response function (SRF) to the right, raising significantly the threshold of response a mean 2.2 degrees C to noxious heating of the skin without significantly affecting the slope of the SRF. MRFS reduced the number of discharges of spinal units evoked by electrical A-alpha,beta-fiber stimulation of hindlimb cutaneous nerves in 4 of 10 units studied. NRMS similarly inhibited the A-alpha,beta-fiber-evoked responses of two of the same four units affected by MRFS but also affected two of the remaining six units not affected by MRFS.(ABSTRACT TRUNCATED AT 400 WORDS)     

Long-term effects of prior heat shock on neuronal potassium currents recorded in a novel insect ganglion slice preparation

Brief exposure to high temperatures (heat shock) induces long-lasting adaptive changes in the molecular biology of protein interactions and behavior of poikilotherms. However, little is known about heat shock effects on neuronal properties. To investigate how heat shock affects neuronal properties we developed an insect ganglion slice from locusts. The functional integrity of neuronal circuits in slices was demonstrated by recordings from rhythmically active respiratory neurons and by the ability to induce rhythmic population activity with octopamine. Under these "functional" in vitro conditions we recorded outward potassium currents from neurons of the ventral midline of the A1 metathoracic neuromere. In control neurons, voltage steps to 40 mV from a holding potential of -60 mV evoked in control neurons potassium currents with a peak current of 10.0 +/- 2.5 nA and a large steady state current of 8.5 +/- 2.6 nA, which was still activated from a holding potential of -40 mV. After heat shock most of the outward current inactivated rapidly (peak amplitude: 8.4 +/- 2.4 nA; steady state: 3.6 +/- 2.0 nA). This current was inactivated at a holding potential of -40 mV. The response to temperature changes was also significantly different. After changing the temperature from 38 to 42 degrees C the amplitude of the peak and steady-state current was significantly lower in neurons obtained from heat-shocked animals than those obtained from controls. Our study indicates that not only heat shock can alter neuronal properties, but also that it is possible to investigate ion currents in insect ganglion slices.     

Rhythmic neuronal interactions and synchronization in the rat dorsal column nuclei

Single-unit and multiunit activities were recorded from dorsal column nuclei of anesthetized rats in order to study the characteristics of the oscillatory activity expressed by these cells and their neuronal interactions. On the basis of their firing rate characteristics in spontaneous conditions, two types of dorsal column nuclei cell have been identified. Low-frequency cells (74%) were silent or displayed a low firing rate (1.9+/-0.48 spikes/s), and were identified as thalamic-projecting neurons because they were activated antidromically by medial lemniscus stimulation. High-frequency cells (26%) were characterized by higher discharge rates (27.2+/-5.1 spikes/s). None of them was antidromically activated by medial lemniscus stimulation. Low-frequency neurons showed a non-rhythmic discharge pattern spontaneously which became rhythmic under sensory stimulation of their receptive fields (48% of cases; 4.8+/-0.23Hz). All high-frequency neurons showed a rhythmic discharge pattern at 13.8+/- 0.68Hz either spontaneously or during sensory stimulation of their receptive fields. The shift predictor analysis indicated that oscillatory activity is not phase-locked to the stimulus onset in either type of cell, although the stimulus can reset the phase of the rhythmic activity of high-frequency cells. Cross-correlograms between pairs of low-frequency neurons typically revealed synchronized rhythmic activity when the overlapping receptive fields were stimulated. Rhythmic synchronization of high-frequency discharges was rarely observed spontaneously or under sensory stimulation. High-frequency neuronal firing could be correlated with the low-frequency neuronal activity or more often with the multiunit activity during sensory stimulation. Moreover, the presence of oscillatory activity modulated the sensory responses of dorsal column nuclei cells, favoring their responses.These findings indicate that thalamic-projecting and non-projecting neurons in dorsal column nuclei exhibited distinct oscillatory characteristics. However, both types of neuron may be entrained into an oscillatory rhythmic pattern when their overlapping receptive fields are stimulated, suggesting that in those conditions the dorsal column nuclei generate a populational oscillatory output to the somatosensory thalamus which could modulate and amplify the effectiveness of the somatosensory transmission.     

Response, thermal regulatory threshold and thermal breakdown threshold of restrained RF-exposed mice at 905 MHz

The objective of this study was the determination of the thermal regulatory and the thermal breakdown thresholds for in-tube restrained B6C3F1 and NMRI mice exposed to radiofrequency electromagnetic fields at 905 MHz. Different levels of the whole-body averaged specific absorption rate (SAR = 0, 2, 5, 7.2, 10, 12.6 and 20 W kg(-1)) have been applied to the mice inside the 'Ferris Wheel' exposure setup at 22 +/- 2 degrees C and 30-70% humidity. The thermal responses were assessed by measurement of the rectal temperature prior, during and after the 2 h exposure session. For B6C3F1 mice, the thermal response was examined for three different weight groups (20 g, 24 g, 29 g), both genders and for pregnant mice. Additionally, NMRI mice with a weight of 36 g were investigated for an interstrain comparison. The thermal regulatory threshold of in-tube restrained mice was found at SAR levels between 2 W kg(-1) and 5 W kg(-1), whereas the breakdown of regulation was determined at 10.1 +/- 4.0 W kg(-1)(K = 2) for B6C3F1 mice and 7.7 +/- 1.6 W kg(-1)(K = 2) for NMRI mice. Based on a simplified power balance equation, the thresholds show a clear dependence upon the metabolic rate and weight. NMRI mice were more sensitive to thermal stress and respond at lower SAR values with regulation and breakdown. The presented data suggest that the thermal breakdown for in-tube restrained mice, whole-body exposed to radiofrequency fields, may occur at SAR levels of 6 W kg(-1)(K = 2) at laboratory conditions.