Effect of age and long-term stress experience on adaptation to stress analgesia in mature rats: role of opioids.

The effects of aging and previous long-term stress on development of tolerance to stress-induced analgesia were evaluated in male Sprague-Dawley rats exposed to intermittent cold water swims (ICWS) in 2 degrees C water (eighteen 10-s exposure, three/min) on 15 consecutive days. Analgesia was measured by the tail-flick test prior to and 30 min after ICWS. In young rats (4 months), tolerance developed faster and asymptotic tolerance was acquired sooner and was more complete than in older rats (15-16 months). Previous long-term exposure (but not the age at which it occurred) accelerated the development and acquisition of asymptotic tolerance to reexposure. Naltrexone (10 mg/kg, ip) partially and completely reversed tolerance to ICWS analgesia in 4- and 9-10-month-old rats, respectively, results suggesting that the opioids are involved in ICWS-analgesia tolerance in both young and old mature rats. In young animals, a second mechanism, naltrexone-insensitive, may be responsible for at least some of the differences in ICWS tolerance found between young and old mature adult rats.

Refinement of the alpha aminooleic acid bioprosthetic valve anticalcification technique.

BACKGROUND: Aminooleic acid treatment has been demonstrated to prevent porcine valve calcification and to protect valvular hemodynamic function. Initial enthusiasm was tempered by histologic studies of these AOA valves, which showed cuspal hematomas, structural loosening, and surface roughening. This prompted a systematic review of the AOA treatment process. Unsolubilized particles of alpha aminooleic acid present in the treatment solution were identified as the cause of mechanical abrasion of valve cusps during processing. These particles were eliminated with a revamped protocol, which included filtration of the AOA solution before valve preparation. METHODS: Porcine aortic valve cusps treated with this modified AOA protocol (AOA II) were studied in a rat subdermal implant model of mineralization. A juvenile sheep trial was then used to confirm the antimineralization effects of AOA II on glutaraldehyde-fixed porcine aortic roots in a circulatory model of accelerated calcification. RESULTS: Retrieved AOA II-treated cusps from the subdermal model were markedly less calcified than control cusps (AOA II, 1 +/- 0, 17 +/- 4, 23 +/- 6, and 17 +/- 10 versus control, 189 +/- 14, 251 +/- 16, 250 +/- 14, and 265 +/- 10 mg calcium/mg sample at 4, 8, 12, and 16 weeks, respectively; p < 0.0001). Morphologic examination of the AOA II cusps of the valves retrieved from the sheep demonstrated freedom from the structural loosening, surface roughening, and hematoma formation that had limited the utility of the original AOA preparation technique. Cusps from AOA II-treated porcine roots had significantly less calcium than control cusps (AOA II, 5.5 +/- 3.0 mg/g; control, 91.2 +/- 19.5 mg/g; p = 0.0004). The aortic walls had similar levels of calcification (AOA II, 156 +/- 73 mg/g; control, 159 +/- 10 mg/g; p = not significant). CONCLUSIONS: These data suggest that the modified AOA technique warrants further evaluation as an antimineralization treatment for glutaraldehyde-fixed porcine bioprostheses.

Peripheral mechanisms of olfactory discrimination of complex mixtures by the spiny lobster: no cell types for mixtures but different contributions of the cells to the across neuron patterns.

Toward understanding mechanisms of olfactory discrimination, we have examined the existence of cell types and the role of cells in the coding of odorant quality in the olfactory organ of the spiny lobster. The results consisted of responses of 30 antennular chemoreceptor cells to 8 behaviorally discriminable complex stimuli--4 natural extracts and 4 artificial mixtures, each at 3 concentrations. Multidimensional scaling and cluster analysis failed to identify unequivocal cell types, but rather suggested a continuum of cellular response profiles. The lack of cell types suggests that the code for the quality of natural odorants in this system is a population code. The distribution of cells along the response continuum was based on any of many features of their response profiles. The most effective stimulus (= best stimulus) and the least effective stimulus (= least stimulus), two features of the response profiles, could only partially explain the differences in response profiles of cells. Nonetheless, cells with different response profiles were shown to have different functions in odorant coding. Most cells contribute to some degree to the discrimination of any two stimuli, but a cell's contribution to the discrimination of two stimuli is usually disproportionally robust when those two stimuli produce very different responses in that cell.

Non-reciprocal cross-adaptation of spiking responses of individual olfactory receptor neurons of spiny lobsters: evidence for two excitatory transduction pathways.

Single-unit spiking responses of 72 olfactory receptor neurons (ORNs) in the olfactory organ of the spiny lobster Panulirus argus were recorded extracellularly during presentation of a set of seven odorant stimuli (adenosine-5'-monophosphate, ammonium chloride, betaine, L-cysteine, L-glutamate, D,L-succinate and taurine) and analyzed in order to evaluate the response specificities of single ORNs and the independence of receptor sites. Individual ORNs often had narrow excitatory response spectra, but the most excitatory compound was different from neuron to neuron. These results suggest that these compounds can exert most of their excitatory effects through relatively independent receptor site types. To determine the relative independence of excitatory transduction processes in single ORNs for these stimuli, single-unit spiking responses of these neurons under conditions of self- and cross-adaptation were analyzed. The results demonstrate extensive cross-adaptation between pairs of the seven stimuli. When averaged across all neurons and all cross-adaptation conditions, cross-adaptation resulted in a mean reduction of 81% of the unadapted response. However, there were differences in the degree and pattern of adaptation for different pairs of compounds and for different neuron types (defined by most excitatory or 'best' chemical). For a given neuron type, there were significant levels of non-reciprocal cross-adaptation: neurons cross-adapted more when adapted to their best chemical than when adapted to their non-best chemicals. These results suggest the existence of two excitatory transduction pathways within an olfactory receptor neuron: one pathway activated exclusively by the best chemical and a second pathway activated by a broader spectrum of chemicals.

Effects of stimulating the subcoeruleus-parabrachial region on the non-noxious and noxious responses of T1-T5 spinothalamic tract neurons in the primate.

The effects of electrical stimulation of the subcoeruleus-parabrachial (SC-PB) region on the discharge rate of upper thoracic spinothalamic tract (STT) neurons were investigated in 21 monkeys anesthetized with alpha-chloralose. STT cells were antidromically activated from the medial thalamus (MT) and the ventral posterior lateral nucleus (VPL) and received viscerosomatic convergent input from the cardiopulmonary sympathetic afferents and the left chest-forearm region. Stimulation of the SC-PB region inhibited the activity of all 30 STT neurons studied in the T1-T5 regions of the spinal cord. The minimum average current required to decrease the discharge rate of 22 cells exhibiting spontaneous activity was 89 +/- 10 microA (100 Hz, 100 microseconds duration). Currents as high as 300 microA completely inhibited the activity of most cells. Examination of the importance of frequency of stimulation from the SC-PB area on 8 cells revealed that impulses of at least 40 Hz (208 +/- 37 microA, 100 microseconds duration) were necessary to inhibit the spontaneous activity by 60%. Higher frequencies produced greater degrees of inhibition. Stimulation of the SC-PB region also inhibited the response of 23 of 23 neurons excited by noxious pinch and 11 of 11 wide dynamic range cells stimulated by innocuous input such as blowing or brushing hair. No differences in the inhibition produced by SC-PB stimulation on cells projecting to VPL (n = 20), MT (n = 5), or both VPL and MT (n = 5) were observed. These results demonstrate that the SC-PB region may be an important brainstem site for descending inhibition of both noxious and innocuous somatic input to upper thoracic STT cells in the primate.

A physiological and pharmacological analysis of the electrodermal response in the rat.

Electrodermal responses (EDR) of the sympathetic-cholinergic sudomotor system were elicited in the footpads of the hindpaws of anesthetized rats. The most reactive CNS loci were caudal to the region of the posterior hypothalamus. Peripherally evoked responses were elicited by electrical stimulation of the decentralized tibial nerve. The amplitude of these evoked EDR was stable over time and both the centrally and peripherally elicited responses were frequency-dependent. Atropine (200 micrograms/kg) depressed the EDR elicited by both peripheral and central stimulation whereas hexamethonium (20 mg/kg) only inhibited the central EDR. Clonidine had no effect on the EDR evoked at the periphery but produced a significant dose-dependent depressant effect on the centrally evoked EDR; this effect was partially antagonized by yohimbine (0.75 mg/kg). It is suggested that the rat is a suitable species for the use of the sudomotor system in the investigation of adrenergic agents which are thought to have a central sympatho-inhibitory action.

Cold water stress analgesia in rats: differential effects of naltrexone.

Cold water swim (CWS, 2 degrees C, 3.5 min) decreases the responsiveness to nociceptive stimuli in rats. The influence of various parameters of the CWS condition on stress-induced analgesia were evaluated by means of naltrexone effects. Naltrexone dose-dependently (but significantly only at high doses--21 mg/kg) partially antagonized 3.5 minute continuous CWS analgesia. Its effect was proportional to the duration of CWS. Naltrexone (14 mg/kg) significantly antagonized intermittent CWS-analgesia (18 10-sec exposures, 3/min) and enhanced the analgesia induced by 60 consecutive exposures (1 sec each, 12/min). These results demonstrate that naltrexone differentially affects CWS-analgesia, depending on specific parametric conditions of the stressor. In addition to activation of a non-specific naltrexone-insensitive analgesia-inducing system (not reduced by the drug in all the conditions studied) there appear to be three naltrexone sensitive systems: (1) a non-opioid analgesia-inducing system which mediates continuous CWS-analgesia; (2) an opioid analgesia-inducing system, involved in intermittent CWS-analgesia; and (3) a naltrexone-sensitive system which opposes the analgesic effect of 60 consecutive exposures. Thus, a highly specific relationship exists between certain parameters of the cold water stressor and the nature of the mechanisms which subserve the induced analgesia.

Amide cross-linking: an alternative to glutaraldehyde fixation.

BACKGROUND AND AIMS OF THE STUDY: A new fixation method for bioprosthetic tissues is being developed, which does not utilize the standard glutaraldehyde treatment. This method, referred to as Ultifix, uses a coupler and a coupling enhancer with or without one or more coupling agents. It fixes the tissue by linking the amine and the carboxyl moieties through amide bonds either directly, or indirectly when coupling agents form bridges. The amide bonds thus formed are more stable than the Schiff-base bonds formed by glutaraldehyde. All compounds used during the fixation process and their by-products are water-soluble, and are easily removed by washing. In addition, the by-products are not toxic, as opposed to glutaraldehyde, which induces toxic reactions after implantation. The tests described in the manuscript were specifically aimed at evaluating the cross-linking efficacy of the process on heart valve tissues, as well as their resistance to calcification in the rat model. METHODS: Porcine aortic roots and porcine pericardium were fixed using the coupling agents 1,6-hexane diamine (DIA) and suberic acid (SUA) in the presence of the coupler 1-ethyl-3(-3 dimethyl aminopropyl) carbodiimide hydrochloride (EDC) and the coupling enhancer N-hydroxysulfosuccinimide (sulfo-NHS). The tissues were then evaluated for their resistance to thermal denaturation, to enzymatic digestion, and to calcification when implanted subdermally in rats for two, four, eight and 16 weeks. RESULTS: The results demonstrate that the cusps and the wall of porcine aortic roots, and porcine pericardium, are as well stabilized and as cross-linked by Ultifix as they are by the standard glutaraldehyde method. In addition, the cusps of the porcine aortic root and the porcine pericardium, but not the wall of the porcine aortic root, calcify minimally and significantly less when implanted subdermally for up to 16 weeks in three week old rats than the control material fixed with glutaraldehyde. CONCLUSION: The Ultifix process of cross-linking bioprosthetic heart valves may thus be a good alternative to the standard glutaraldehyde process of fixation, with increased durability and without toxic effects.

A comparison between glutaraldehyde and diepoxide-fixed stentless porcine aortic valves: biochemical and mechanical characterization and resistance to mineralization.

As previously reported, we found that the fixation rate and thermal denaturation (shrink) temperature of the diepoxide-fixed tissue could be controlled by varying the concentration of the fixative as well as by adding alcohol and/or sodium chloride to the solution. In contrast to prior experience, however, we now found that the epoxide-fixed leaflets exhibited significantly higher resistance to mineralization compared to controls, but only when the tissue had not been exposed to phosphate ion.

Naltrexone antagonizes the biobehavioral adaptation to cold water stress in rats.

The reported studies on the development of tolerance to the analgesic effects of stress have been mostly concerned with the involvement of opioid or non-opioid substances in stress-induced analgesia (SIA). To further investigate the processes involved in SIA tolerance, rats were exposed to forced intermittent cold water swim (ICWS, 18 exposures, 3/min, 10 sec each) on 16 consecutive days. On days 15 and 16, they were injected prior to swim with saline and naltrexone (10 mg/kg), respectively. During swim, three types of readily identifiable behaviors were observed. They may be characterized by immobility and horizontal floating (Type I), intensive activity and escape attempts (Type II), and passivity and "behavioral despair" (Type III). In the acute condition, only Type II and Type III appear in sequence. In the chronic condition, the sequence of behaviors is: Type I, Type II, and Type III. Thirty minutes after swim, analgesia, core temperature, and degree of inactivity were measured. With chronic exposure, tolerance developed to the analgesia, core hypothermia and hypoactivity induced by the ICWS. Type I behavior appeared on day 3 or 4 and persisted throughout the chronic treatment. Type II behavior did not adapt. Naltrexone (10 mg/kg) antagonized the adaptive aspect of all those variables where adaptation or tolerance were found (analgesia, hypoactivity, core hypothermia, and Type I behavior) but had no effect on Type II behavior where no adaptation was observed. It is suggested that the endorphins have a functional role in the behavioral and and physiological adaptation to aversive stressful environmental situations.

Intermittent cold water stress-analgesia in rats: cross-tolerance to morphine.

Continuous cold water swim ( CCWS , 3.5 min, 2 degrees C) induces a non-opiate type of analgesia since 14 mg/kg of naltrexone or 20 mg/kg of naloxone only partially antagonize this stress-induced analgesia (SIA) and since there is no cross-tolerance between CCWS and morphine-analgesia. Intermittent cold water swim ( ICWS ) analgesia is significantly antagonized by naltrexone (14 mg/kg). These studies suggested that CCWS -analgesia is mediated by non-opioid systems, while ICWS -analgesia acts through a system that also mediates morphine analgesia. The hypothesis that ICWS -analgesia shares a common opioid pathway with morphine-analgesia, but not with CCWS -analgesia, was further tested by cross-tolerance studies in rats. The results showed a complete cross-tolerance to morphine analgesia in ICWS -tolerant animals,, but no cross-tolerance in animals. This suggests that morphine- and ICWS -analgesia partially share a common pathway, ICWS acting probably at levels "downstream" from the opiate-sensitive site, while CCWS induces analgesia by acting on a different system which is not mediated by opioids.

Effect of AOA on glutaraldehyde-fixed bioprosthetic heart valve cusps and walls: binding and calcification studies.

Alpha-aminooleic acid (AOA), a potent, non-toxic and biocompatible anticalcification agent, has been shown to be effective for glutaraldehyde-fixed valves in rat and juvenile sheep models, and is used for the treatment of Medtronic heart valve bioprostheses currently in clinical trials. In the pre-clinical sheep study of a stentless aortic root, the treatment with AOA prevented calcification of the cusps, but not of the wall. The experiments described in this manuscript were designed to investigate a possible relationship between the binding of AOA and the differential treatment efficacy in the cusp and the wall, and to improve the anticalcification effect of the AOA treatment in the wall. Glutaraldehyde-fixed porcine roots were treated with [14C]-AOA for binding studies, and with non-radioactive AOA for calcification studies for rat subdermal implants. The results indicate that a) the AOA treatment did reduce wall calcification, but only temporarily, b) the low efficacy of the AOA treatment on the wall was probably due to the limited penetration of AOA, and c) increasing the volume of the AOA solution during treatment significantly increased the content of AOA in the wall, and significantly decreased wall calcification. This study suggests that AOA efficacy in the wall may be hindered because of the physical characteristics of the wall, and that wall calcification may be prevented by developing methods aimed at increasing AOA penetration into the wall.

Neural coding of quality of complex olfactory stimuli in lobsters.

1. Extracellular responses to complex biologically relevant stimuli were recorded from 30 primary olfactory cells from excised antennules of spiny lobsters. The stimulus types were natural extracts of crab, mullet, oyster, and shrimp and artificial mixtures of crab, mullet, oyster and shrimp based on the chemical composition of the related extracts. All stimulus types were presented at the following three concentrations: 0.005, 0.05, and 0.5 mM. 2. The responses were expressed as number of spikes per 5 s. Response magnitude increased significantly as a function of concentration. It was significantly greater for the natural extracts than for the related artificial mixtures but was not significantly different among stimulus types within either natural extracts or artificial mixtures. 3. The cells were broadly tuned to all stimuli. Tuning slightly, but significantly, broadened as a function of stimulus concentration. 4. Multidimensional scaling (MDS) was used to evaluate similarities and dissimilarities among stimuli based on population responses. The artificial mixtures and the natural extracts were analyzed separately. Dimensionality of spatial configuration was based on the following three criteria: stress values, squared correlation values, and relevance to quality coding. 5. When applied to the original data, MDS distributed the stimuli in a two-dimensional space where the location of each stimulus was based mainly on stimulus concentration. The results of a simple standardization procedure showed that this distribution resulted mostly from the significant effect of concentration on one of the two features of population responses, which is the absolute magnitude. This standardization procedure equalized the three concentrations in terms of absolute magnitude of evoked response. Consequently, the neural population responses of the 12 stimuli (4 types X 3 concentrations) could be compared based only on their across-neuron patterns (ANPs) (relative amount of activity across neurons). 6. When stress and squared correlation values were used as criteria for dimensionality, the configuration of the artificial mixtures space was best derived from dimensions 1, 2, and 3 of the three-dimensional resolution. When relevance to quality coding was used, the configuration of the artificial mixtures space was best derived from dimensions 1, 3, and 4 of the four-dimensional resolution. Whether stress and squared correlation values or relevance to quality coding were used, the four types of stimuli occupied nonoverlapping spaces.(ABSTRACT TRUNCATED AT 400 WORDS)

Chronic stress, aging and morphine analgesia: chronic stress affects the reactivity to morphine in young mature but not old rats.

The effect of chronic stress on analgesic responsiveness to morphine was studied in mature rats of different ages. Chronic stress consisted of eighteen 10-sec exposures (three/min) in 2 degrees C water for 54 consecutive days. From day 20, at 4-day intervals, the rats were not stressed but instead given i.p. injections of, sequentially: 10, 0 (saline), 5, (2 mg/kg of naltrexone) + 10, 2.5, 1, 20 and 10 mg/kg of morphine sulfate. On these days, tail-flick latencies were measured before and 5, 10, 15, 30, 60, 120 and 180 min after morphine injection. The responsiveness to morphine was significantly altered by exposure to chronic stress in young, mature rats (4 months) as compared to control rats. A dose of 10 mg/kg of morphine induced a diphasic response. Initial increased tail-flick reflexes (at 5 min after injection) were followed by slight but nonsignificant decreased responses to the tail-flick test. At 30 min, the dose-response curve was shifted to the right. No alteration of the response to morphine was observed in older rats (15-17 months) exposed to chronic stress, unless they had been submitted to chronic stress at 4 months of age. In addition, the response after a second exposure to chronic stress to morphine was highly dependent on, and similar to, the age-dependent response after a first exposure. These results demonstrate that the endogenous opiate system can be altered by exposure to chronic stress even after maturation has occurred and that this alteration has long-term effects on the reactivity to morphine.

Independent components of the neural population response for discrimination of quality and intensity of chemical stimuli.

The responses of a population of 30 olfactory receptor cells from spiny lobsters to 8 behaviorally relevant complex types of stimuli at 0.005, 0.05 and 0.5 mM were analyzed using multidimensional scaling to evaluate their potential for coding quality and intensity. A discrimination index was derived from the resulting stimulus coordinates, which takes into account the response similarities within type/concentration and the response dissimilarities between types/concentrations. The results indicate that quality and intensity can be discriminated by separate components of the response of the population of neurons: quality by the pattern of responses produced across the neuronal population, and intensity by the absolute response magnitude.

Effects of intracardiac bradykinin on T2-T5 medial spinothalamic cells.

Effects of injecting bradykinin (2 micrograms/kg) into the left atrium on spinothalamic tract neurons projecting to medial thalamus (M-STT cells), to the ventral posterior lateral nucleus of the thalamus (L-STT cells), or to both (LM-STT cells) were examined in 18 monkeys (Macaca fascicularis) anesthetized with alpha-chloralose. Bradykinin increased cell activity in 11/16 M-STT cells, 10/15 L-STT cells, and 4/7 LM-STT cells. One M-STT cell was inhibited. Peak responses to bradykinin of the three cell groups were not different. LM-STT cells began to respond and reached peak responses slightly earlier than the other two groups. Six M-STT, four L-STT, and two LM-STT cells became entrained to the cardiac cycle during their responses to bradykinin. Responses to bradykinin were not dependent on the type of somatic input or cell location. Responding cells most often received A delta- and C-fiber sympathetic input, but some responding cells had only A delta-input. These results demonstrate that in addition to L-STT cells STT cells projecting to the medial thalamus respond to a potentially noxious cardiac stimulus. These cells may participate in the motivational-affective component of cardiac pain.

T2-T5 spinothalamic neurons projecting to medial thalamus with viscerosomatic input.

Spinothalamic tract neurons projecting to medial thalamus (M-STT cells), ventral posterior lateral nucleus (VPL) of the thalamus (L-STT cells), or both thalamic regions (LM-STT cells) were studied in 19 monkeys anesthetized with alpha-chloralose. Twenty-seven M-STT cells were antidromically activated from nucleus centralis lateralis, nucleus centrum medianum, or the medial dorsal nucleus. Stimulation of VPL elicited antidromic responses from 22 cells and 13 cells were activated from both VPL and medial thalamus. Antidromic conduction velocities of M-STT cells were significantly slower than those of L-STT or LM-STT cells. M-STT cells were located in laminae I, IV, V, and VII with greater numbers found in the deepest laminae. L-STT cells were located mostly in lamina IV, whereas most LM-STT cells were found in lamina V. Twenty-four of 27 M-STT cells, all L-STT cells, and all LM-STT cells received input from both cardiopulmonary sympathetic and somatic afferent fibers. WDR cells were most common among the L-STT and LM-STT groups, whereas HT cells were the most common class in the M-STT cell group. Excitatory receptive fields of M-STT cells were large, and often bilateral. Receptive fields of L-STT cells were simple and never bilateral. Receptive fields of LM-STT cells could be similar to M-STT or L-STT cells. Thirty-three percent of the M-STT cells, 37% of the L-STT cells, and 62% of the LM-STT cells had inhibitory receptive fields. Inhibition was elicited most often by a noxious pinch of the hindlimbs. Sixteen of 23 (70%) M-STT cells received C-fiber cardiopulmonary sympathetic input in addition to A-delta-fiber input. The other 7 cells received only A-delta-fiber input. Only 45% of the L-STT cells and 38% of the LM-STT cells received both A-delta- and C-fiber inputs. The maximum number of spikes elicited by A-delta-input was related to segmental locations for L-STT cells with greatest responses in T2 and lesser responses in more caudal segments; however, no such trend was apparent for M-STT cells or for responses to C-fiber input for either group. Electrical stimulation of the left thoracic vagus nerve inhibited 7 of 18 M-STT cells, 10 of 16 L-STT cells, and 6 of 12 LM-STT cells. These results are the first description of visceral input to cells projecting to medial thalamus.(ABSTRACT TRUNCATED AT 400 WORDS)

Periventricular gray inhibition of thoracic spinothalamic cells projecting to medial and lateral thalamus.

Effects of electrical stimulation of the periventricular gray (PVG) on spinothalamic tract (STT) cell activity were determined in 19 anesthetized monkeys (Macaca fascicularis). Twenty-two STT cells projected to the ventral posterior lateral nucleus (L-STT cells), 11 to the medial thalamus (M-STT cells), and 9 to both thalamic regions (LM-STT cells). All cells had somatic receptive fields and responded to electrical stimulation of cardiopulmonary sympathetic afferent fibers. PVG stimulation inhibited activity of 41 of 42 STT cells. Degree of inhibition of background activity was related to intensity and frequency. Stimulus currents of 300 microA or less completely silenced background activity of most cells. Thresholds for stimulus current averaged 100 +/- 20 microA and were unrelated to cell projection site, laminar location, or type of somatic or visceral input. However, lowest thresholds were found when the PVG electrodes were located within 0.5 mm of the third ventricle in the dorsomedial hypothalamus or nucleus reuniens of the thalamus. PVG stimulation inhibited responses of 22 of 22 cells to intracardiac injections of bradykinin. Bradykinin (2 micrograms/kg) increased cell activity from 15 +/- 3 to 31 +/- 5 spikes/s (P less than 0.01), and PVG stimulation (380 +/- 40 microA) reduced activity to 9 +/- 3 spikes/s (P less than 0.001). PVG stimulation inhibited responses of 33 of 33 STT cells to noxious pinch of skin or skin and muscle and responses of 8 of 8 cells to hair movement. Degree of inhibition of cell responses to noxious pinch was not significantly different from inhibition of responses to bradykinin. Effects of PVG stimulation on activity of six STT cells were studied before and after bilateral lesions were made in the dorsolateral funiculus (DLF). In no case did the lesions abolish or attenuate inhibitory effects of PVG stimulation. These results suggest that PVG may participate in descending inhibition of STT cells including cells mediating cardiac pain. The descending pathways are not located in the DLF. Further, descending inhibitory systems modulate STT cells projecting to both medial and lateral thalamus.

Responses of olfactory receptor cells of spiny lobsters to binary mixtures. I. Intensity mixture interactions.

1. Neural coding of chemical mixtures was studied with the use of the peripheral olfactory system of the spiny lobster. The occurrence of mixture interactions (i.e., where the observed response to a mixture deviates significantly from the expected response) in individual cells and the effect of such mixture interactions on the coding of odorant intensity by populations of cells were examined. 2. Extracellular recordings of spiking activity of 98 primary olfactory receptor cells in the antennules were measured in response to seven compounds [adenosine-5'-monophosphate (AMP), betaine (Bet), L-cysteine (Cys), L-glutamate (Glu), ammonium chloride (NH4), DL-succinate (Suc), and taurine (Tau)] and their binary mixtures. To identify mixture interactions, observed responses to a range of concentrations of a binary mixture were compared with the predicted responses based on three mathematical models: a single receptor model, which assumes that the two compounds of a mixture bind to the same receptor site; a multiple receptor model, which assumes that the two compounds bind to two independent receptor sites; and a mixed composition receptor model, which incorporates our current state of knowledge of transduction processes in olfactory receptor cells of spiny lobsters. 3. Mixture interactions in individual cells were common: statistically significant mixture interactions were observed in 25% of the possible cases (Fig. 5). Suppression was much more common than enhancement. 4. Mixture interactions had significant effects on the absolute response magnitudes for a population of cells, which could be used as the neural code for stimulus intensity in this system. These effects are called intensity mixture interactions (Figs. 6-11). Intensity mixture interactions occurred for approximately 50% of the binary mixtures and were almost exclusively suppression (Figs. 12 and 13). The intensity mixture interactions were concentration independent. 5. The results suggest that mixture interactions in individual olfactory cells can result in intensity mixture interactions in the neuronal population such that there is a decrease in sensitivity to binary mixtures relative to what is expected based on the responses to individual components of the mixtures.

Responses of olfactory receptor cells of spiny lobsters to binary mixtures. II. Pattern mixture interactions.

1. The effect of mixture interactions in individual olfactory receptor cells of the spiny lobster on neural coding of odorant quality of binary mixtures and their components is examined in this paper. Extracellular responses of 98 olfactory receptor cells in the antennules of spiny lobsters to seven compounds [adenosine-5'-monophosphate (AMP), betaine (Bet), L-cysteine (Cys), L-glutamate (Glu), ammonium chloride (NH4), DL-succinate (Suc), taurine (Tau)] and their binary mixtures were recorded, and mixture interactions in individual olfactory receptor cells were identified. 2. Coding of odorant quality was evaluated by examining across neuron patterns (ANPs)--the relative response magnitudes across neuronal populations. ANPs are a feature of the neuronal population response and are a possible concentration-independent code of odorant quality in this system, as indicated by previous studies and present results. 3. For most binary mixtures the diversity of types and degrees of mixture interactions across the individual cells of a population of cells resulted in ANPs for each mixture to be different from the ANPs for the components of the mixture and different from the ANP predicted for the mixture from the responses to the components (Figs. 2-10). These effects are called pattern mixture interactions (PMIs). PMIs occurred for most binary mixtures, even those that did not produce statistically significant intensity mixture interactions (IMIs) for this same population of cells. 4. The results suggest that PMIs can influence coding of stimulus quality, in some cases by causing an improvement of the contrast between the quality of mixtures and some of their components.