The effect of firing rate on preoptic neuronal thermosensitivity

1. In anaesthetized rabbits, preoptic single units were recorded having positive or negative thermal coefficients (impulses/sec. degrees C) for changes in preoptic temperature.2. A population of forty-two positive coefficient units was divided into four groups based on their level of firing rate at 38 degrees C. In each group, the average thermoresponse curve was determined by averaging the firing rates of the units at 1 degrees C intervals over the 33-43 degrees C range of preoptic temperatures.3. A population of twenty-six negative coefficient units was divided into three groups based on their firing rates at 38 degrees C. Similar average thermoresponse curves were determined for each group.4. As the level of firing rate increased in the positive coefficient units, the preoptic thermosensitivity progressively decreased at temperatures above 39 degrees C, but generally increased at temperatures below 39 degrees C.5. In the negative coefficient units, preoptic thermosensitivity generally increased (especially above 39 degrees C) as the firing rate at 38 degrees C increased.6. The results indicate that in positive coefficient units the level of firing rate determines the temperature range in which units are most thermosensitive. This range reflects whether a neurone is more likely to function in heat-loss or heat-production responses.7. Since peripheral thermal input affects the level of firing rate of positive coefficient units, a neuronal model is suggested to explain the role of peripheral and central thermal signals in temperature regulation.     

Effect of calcium removal on thermosensitivity of preoptic neurons in hypothalamic slices

Extracellular single-unit activities of thermosensitive neurons were recorded from the medial preoptic area in rat's hypothalamic slices in vitro. Of 256 preoptic units, 74 were warm-units which increased firing rates in response to a rise in slice temperature and 16 units were cold-units having the opposite type of thermosensitivity. Eighteen of 23 warm-units and 3 of 4 cold-units retained their thermosensitivities during perfusion with Ca2+-free/high Mg2+ salt solution. The thermosensitivities of the remaining 5 warm-units were reversibly abolished in the Ca2+ deficient medium. The results suggest that some warm- and cold-sensitive neurons in the medial preoptic area have an inherent thermosensitivity.     

A comparison between total body thermosensitivity and local thermosensitivity in mammals and birds

We have investigated how total body thermosensitivity in various mammalian and avian species (mouse, rat, golden hamster, guinea pig, rabbit, dog, goat, pigeon, duck, goose) is related to their respective local thermosensitivities in the hypothalamus, spinal cord and skin. Local and total thermosensitivities were determined by measuring the relationship between the response of one thermoregulatory effector, metabolic heat production, and the appropriate temperature. Local cooling was performed with chronically implanted, water perfused thermodes, and local thermosensitivities were estimated by relating the maximum activation of metabolic heat production to the induced decreases in local temperature. Total body cooling was achieved by means of chronically implanted intravascular heat exchangers or with thermodes inserted into the lower intestinal tract, and total body thermosensitivity was assessed by relating the rise in metabolic heat production to the induced fall in core temperature. These analyses plus previous estimations derived from the literature show total body thermosensitivity in the different species to range from –4.0 to –12.0 W · kg^–1 · °C^–1. We also measured rabbit spinal cord thermosensitivity and guinea pig hypothalamic and spinal cord thermosensitivity; values for local thermosensitivity in other species were derived from the literature. In all species, local thermosensitivities determined as cold sensitivities in the described way were smaller than the corresponding total body core sensitivities. We conclude that thermosensitive structures outside of the investigated thermosensitive areas contribute a major input to the controller of body temperature, particularly in avian species in which hypothalamic thermosensitivity is lacking. This corresponds to observations in several mammalian and one avian species in which local and total body thermosensitivities were dervied from the responses of an autonomic heat defence effector, respiratory evaporative heat loss.     

Thermosensitivity of preoptic neurones in a hibernator at high and low ambient temperatures

Summary The effect of ambient temperature on the thermosensitivity of preoptic neurones was studied in euthermic golden hamsters. At skin temperatures (T_sk) of 20°C, preoptic units were still responsive to hypothalamic temperatures (T_hy) below 10°C, while at T_sk=36°C these neurones became inactive at T_hy=15°C on the average. These studies suggest that thermoreceptive preoptic neurones, influenced by a high activity of cutaneous cold-receptors, are capable of sensing core temperatures even in deep hibernation.Supported by the Deutsche Forschungsgemeinschaft, Wu 63/2     

Total body thermosensitivity and its spinal and supraspinal fractions in the conscious goose

1. Effects of general body cooling on heat production: an intravascular heat exchanger was used to alter total body temperature. Heat production increased with decreasing body temperature at an average rate of ?12 W/kg·°C. The rate of rise was independent of air temperature. The threshold body temperature below which heat production rose was lower at higher air temperature.
2. Effects of spinal cord cooling: heat production increased with decreasing spinal temperature at an average rate of ?0.3 W/kg·°C. The rate of rise was not clearly affected by air temperature. The spinal threshold temperature was lower at warm ambient conditions. The results suggest that spinal thermosensitivity in the goose represents only a minor fraction of total body thermosensitivity.
3. Effects of head cooling: heat exchangers enclosing the carotid arteries were used to alter the temperature of the blood supplied to the head. Cooling increased heat production. When the thermosensitivity of the area, which was affected by the heat exchanger, was calculated from the relationship between changes of heat production and brain temperature, values between ?0.74 and ?1.65 W/kg·°C were obtained. Measurements of brain, spinal cord and head skin temperatures suggest that the thermosensitive structures which mediated the responses, were predominantly situated in the brain.

     

Effects of air constituents on thermosensitivities of preoptic neurons: hypoxia versus hypercapnia

The effects of hypoxia (10% O₂) on the thermosensitivities of preoptic neurons were studied in urethanized rats and compared to the effects of hypercapnia (10% CO₂). This was examined by regression of neuronal activity on preoptic temperature. During hypoxia, the slope of the regression line increased significantly in 8 (23%) of 35 warmsensitive neurons and decreased in eight other neurons (P<0.05). During hypercapnia, the slope of the regression line decreased significantly in 7 (30%) of the 23 warmsensitive neurons (P<0.05). No neuron was found that significantly increased the slope of the regression line. The effects of hypoxia on thermosensitivities (i.e. the slope of the regression line) of PO neurons differed from those of hypercapnia in chi-square analysis (P<0.05). Responses of the cold-sensitive neurons to hypoxia or hypercapnia did not generally differ from those of the warm-sensitive neurons. During hypoxia and hypercapnia, arterial blood pressure, respiratory frequency, heart rate, and EEG were recorded to examine their relations to neuronal activity. The present results indicate that the thermosensitivities of preoptic neurons are modified by both hypoxia and hypercapnia, but that hypoxic differ from hypercapnic effects.     

Activation of central warm-sensitive neurons and the tail vasomotor response in rats during brain and scrotal thermal stimulation

The effects of preoptic and hypothalamic thermal stimulation on tail skin temperature were observed at different scrotal temperatures. The threshold hypothalamic temperature for tail vasodilation at a scrotal temperature of 40°C was significantly lower than that at a scrotal temperature of either 25°C or 33°C. The effects of scrotal thermal stimulation on tail skin vasodilated by higher hypothalamic temperatures were observed. Cooling the scrotum from 42 to 30°C invariably caused a rapid fall in tail temperature, whereas scrotal cooling from 30 to 25°C did not cause any significant change. Cooling of either the left or right half of the scrotum caused a similar fall in tail temperature. The temperature characteristics of the preoptic hypothalamic thermo-sensitive neurons were determined at scrotal temperatures of 32, 36 and 26°C. The firing rate of warm-sensitive neurons at a given hypothalamic temperature was highest at a scrotal temperature of 36°C, while that of cold-sensitive neurons was lowest at that temperature. The scrotal temperature range over which the number of neurons activated by scrotal warming increased rapidly was between 36 and 39°C when hypothalamic temperature was held at 36–37°C.     

Electrophysiological properties and thermosensitivity of mouse preoptic and anterior hypothalamic neurons in culture

Responses of mouse preoptic and anterior hypothalamic neurons to variations of temperature are key elements in regulating the setpoint of homeotherms. The goal of the present work was to assess the relevance of culture preparations for investigating the cellular mechanisms underlying thermosensitivity in hypothalamic cells. Our working hypothesis was that some of the main properties of preoptic/anterior hypothalamic neurons in culture are similar to those reported by other authors in slice preparations. Indeed, cultured preoptic/anterior hypothalamic neurons share many of the physiological and morphological properties of neurons in hypothalamic slices. They display heterogenous dendritic arbors and somatic shapes. Most of them are GABAergic and their activity is synaptically driven by the activation of alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid/kainate receptors. Active membrane properties include a depolarizing "sag" in response to hyperpolarization, and a low threshold spike, which is present in a majority of cells and is generated by T-type Ca2+ channels. In a fraction of the cells, the low threshold spike repeats rhythmically, either spontaneously, or in response to depolarization. The background synaptic noise in cultured neurons is characterized by the presence of numerous postsynaptic potentials which can be easily distinguished from the baseline, thus providing an opportunity for assessing their possible roles in thermosensitivity. An unexpected finding was that GABA-A receptors can generate both hyper- and depolarizing postsynaptic potentials in the same neuron. About 20% of the spontaneously firing preoptic/anterior hypothalamic neurons are warm-sensitive. Warming (32-41 degrees C) depolarizes some cells, a phenomenon which is Na+-dependent and tetrodotoxin-insensitive. The increased firing rate of warm-sensitive cells in response to warming can be prepotential and/or synaptically driven. Overall, our data suggest that a warm-sensitive phenotype is already developed in cultured cells. Therefore, and despite obvious differences in their networks, cultured and slice preparations of hypothalamic neurons can complement each other for further studies of warm-sensitivity at the cellular and molecular level.     

Thermosensitivity of preoptic neurones in a hibernator (golden hamster) and a non-hibernator (guinea pig)

Summary Thermosensitivity of preoptic units was studied at hypothalamic temperatures (T _hy) ranging from 8–43°C in golden hamsters in a non-hibernating state as well as in guinea pigs. In golden hamsters 2 types of thermoresponsive preoptic neurones were found: 1. Neurones sensitive toT _hy ranging from 10–42°C with an exponential characteristic and very high spontaneous firing rates (29–59 imp/s) atT _hy 36–37°C. 2. Neurones with a bell-shaped temperature-firing rate characteristic, a negative temperature coefficient atT _hy 40–30°C, a maximal activity atT _hy 20–30°C and a positive temperature coefficient (+0.8 to +4 imp/s·°C) even atT _hy close to 10°C. In guinea pigs thermoresponsive preoptic units became inactive or insensitive to thermal stimulation as soon asT _hy fell below 30°C. These results suggest that in hibernators central nervous structures involved in temperature regulation are adapted to maintain their function over the wide range of core temperatures which occur during the different phases of hibernation.Supported by the Deutsche Forschungsgemeinschaft, Project B1. SFB 122.     

The distribution of cutaneous sudomotor and alliesthesial thermosensitivity in mildly heat-stressed humans: an open-loop approach

The distribution of cutaneous thermosensitivity has not been determined in humans for the control of autonomic or behavioural thermoregulation under open-loop conditions. We therefore examined local cutaneous warm and cool sensitivities for sweating and whole-body thermal discomfort (as a measure of alliesthesia). Thirteen males rested supine during warming (+4°C), and mild (−4°C) and moderate (−11°C) cooling of ten skin sites (274 cm²), whilst the core and remaining skin temperatures were clamped above the sweat threshold using a water-perfusion suit and climate chamber. Local thermosensitivities were calculated from changes in sweat rates (pooled from sweat capsules on all limbs) and thermal discomfort, relative to the changes in local skin temperature. Thermosensitivities were examined across local sites and body segments (e.g. torso, limbs). The face displayed stronger cold (−11°C) sensitivity than the forearm, thigh, leg and foot ( P = 0.01), and was 2–5 times more thermosensitive than any other segment for both sudomotor and discomfort responses ( P = 0.01). The face also showed greater warmth sensitivity than the limbs for sudomotor control and discomfort ( P = 0.01). The limb extremities ranked as the least thermosensitive segment for both responses during warming, and for discomfort responses during moderate cooling (−11°C). Approximately 70% of the local variance in sudomotor sensitivity was common to the alliesthesial sensitivity. We believe these open-loop methods have provided the first clear evidence for a greater facial thermosensitivity for sweating and whole-body thermal discomfort.     

Effects of biogenic amines on central thermoresponsive neurones in the rabbit

1. Single unit activities were recorded with five-barrelled micropipettes from the thermo-responsive neurones in the preoptic area and the mid-brain reticular formation in urethanized rabbits. 5-hydroxytryptamine (5-HT), noradrenaline (NA) and acetylcholine (ACh) were applied micro-iontophoretically to the immediate vicinity of the recording cells.2. Out of seventeen warm-responsive neurones recorded in the preoptic area, fifteen neurones responded to 5-HT with the increase in firing rate and two showed no response. Thirteen out of seventeen warm-units decreased their firing rate in response to application of NA and four were not affected. ACh had no effect on any of the warm-units examined.3. Six out of seven cold-units in the preoptic area were depressed by 5-HT, while NA excited five of six units studied. None of the cold-units were influenced by ACh.4. These results are in good agreement with the changes in rectal temperature produced by 5-HT and NA micro-injected into the hypothalamus in rabbits.5. In the mid-brain reticular formation, 5-HT excited all of fourteen cold-responsive neurones. Of these, eight cold-units were depressed and six were unaffected by NA, while ACh excited six units and had no effect on eight units. All of the five warm-responsive units were inhibited by 5-HT and none were influenced by NA. Thus, the responses of reticular thermoresponsive neurones to 5-HT and NA were opposite to those of the preoptic thermo-responsive neurones.     

Heat stress-mediated plasticity in a locust looming-sensitive visual interneuron

Neural circuits are strongly affected by temperature and failure ensues at extremes. However, detrimental effects of high temperature on neural pathways can be mitigated by prior exposure to high, but sublethal temperatures (heat shock). Using the migratory locust, Locusta migratoria, we investigated the effects of heat shock on the thermosensitivity of a visual interneuron [the descending contralateral movement detector (DCMD)]. Activity in the DCMD was elicited using a looming stimulus and the response was recorded from the axon using intracellular and extracellular methods. The thoracic region was perfused with temperature-controlled saline and measurements were taken at 5 degrees intervals starting at 25 degrees C. Activity in DCMD was decreased in control animals with increased temperature, whereas heat-shocked animals had a potentiated response such that the peak firing frequency was increased. Significant differences were also found in the thermosensitivity of the action potential properties between control and heat-shocked animals. Heat shock also had a potentiating effect on the amplitude of the afterdepolarization. The concurrent increase in peak firing frequency and maintenance of action potential properties after heat shock could enhance the reliability with which DCMD initiates visually guided behaviors at high temperature.     

Comparison between hypothalamic thermoresponsive neurons from duck and rat slices

Neuronal thermoresponsiveness in the preoptic and anterior hypothalamic (PO/AH) region of a bird and a mammal were compared in vitro by recording the activity of 48 units from ducks and 37 units from rats in tissue slices subjected to temperature changes. Warm-responsive units were found in similar proportions in duck and rat PO/AH slices. The average degrees of thermoresponsiveness did not differ between the two species. Neurons exhibiting thresholds of warm responsiveness had higher threshold temperatures (2P<0.01) in duck (38.8±0.2° C) than in rat (37.4±0.4° C) slices (means±standard errors). Firing rates at threshold temperatures and thermoresponsiveness below and above thresholds did not differ between ducks and rats. During synaptic blockade in a Ca²⁺-free/high-Mg²⁺ medium, warm-responsiveness was retained in 9 out of 13 units in duck slices and in 8 out of 13 units in rat slices. In two instances in ducks and in one case in rats positive temperature coefficients were converted into negative temperature coefficients. Among two cold-responsive units tested in duck slices one retained its cold-responsiveness. It is concluded that in vitro evaluation of PO/AH neuronal thermoresponsiveness in a bird and a mammal has not revealed differences at the single unit level which might explain the diverging contributions of the avian and mammalian hypothalamus to deep body temperature perception.     

Thermoregulatory Control of Sympathetic Fibres Supplying the Rat's Tail

We investigated the thermoregulatory responses of sympathetic fibres supplying the tail in urethane-anaesthetised rats. When skin and rectal temperatures were kept above 39 °C, tail sympathetic fibre activity was low or absent. When the trunk skin was cooled episodically by 2–7 °C by a water jacket, tail sympathetic activity increased in a graded fashion below a threshold skin temperature of 37.8 ± 0.6 °C, whether or not core (rectal) temperature changed. Repeated cooling episodes lowered body core temperature by 1.3–3.1 °C, and this independently activated tail sympathetic fibre activity, in a graded fashion, below a threshold rectal temperature of 38.4 ± 0.2 °C. Tail blood flow showed corresponding graded vasoconstrictor responses to skin and core cooling, albeit over a limited range. Tail sympathetic activity was more sensitive to core than to trunk skin cooling by a factor that varied widely (24-fold) between animals. Combined skin and core cooling gave additive or facilitatory responses near threshold but occlusive interactions with stronger stimuli. Unilateral warming of the preoptic area reversibly inhibited tail sympathetic activity. This was true for activity generated by either skin or core cooling. Single tail sympathetic units behaved homogeneously. Their sensitivity to trunk skin cooling was 0.3 ± 0.08 spikes s⁻¹°C⁻¹ and to core cooling was 2.2 ± 0.5 spikes s⁻¹°C⁻¹. Their maximum sustained firing rate in the cold was 1.82 ± 0.35 spikes s⁻¹.     

Mechanoreceptor response to mechanical and thermal stimuli in the glans penis of the dog

In the dog, we isolated 126 mechanoreceptive afferent fibers of the A-delta myelinated fiber class from the dorsal nerve of the penis using microdissection and extracellular electrophysiological techniques. Receptive fields on the glans penis were stimulated with a computer-controlled mechanostimulator and Peltier effect thermostimulator. The great majority of units were categorized as either rapidly adapting (RA) or slowly adapting (SA) and were located primarily proximally and distally, respectively, on the glans. In comparison to values from other glabrous skin regions in other species, mean displacement and force thresholds of penile mechanoreceptors were high, whereas the mean velocity thresholds were low. SA units, generally poor encoders of static displacement, were distinguishable into two types based on static response firing pattern but were not homologous to either the SA I or SA II mechanoreceptors found in other skin regions. Fifty-five units were given simultaneous mechanical and thermal stimulation. Very few units responded to pure thermal stimulation or increased their discharge frequency to skin cooling. Warm receptive-field temperatures between 35 and 43 degrees C increased mechanical sensitivity, measured by displacement and velocity coding functions, in almost all units tested. We conclude that canine penile mechanoreceptors, capable of encoding a variety of skin movements when the penis is warm, provide the spinal cord with the sensory input necessary to drive the spinal sexual reflexes. However, many appear to be at least physiologically different from mechanoreceptors native to other skin areas.     

Osmosensitivity of preoptic thermosensitive neurons in hypothalamic slices in vitro

The effects of local osmotic changes on the activity of preoptic thermosensitive neurons were investigated in rat hypothalamic slices in vitro. Thirty-seven (53%) of 70 neurons recorded from the medial preoptic nucleus (MPO) (66% of thermosensitive neurons and 12% of thermally insensitive neurons) changed their firing rates in response to alterations in local osmolality of less than 15 mOsm/kg. The minimum change in osmolality to produce the neuronal response for six neurons tested was found to be less than 5 mOsm/kg. Statistical analysis revealed that there was a higher incidence of warm-sensitive neurons inhibited by hyperosmolality (50% of warm-units) and of thermally insensitive neurons which were osmotically insensitive (88%). None of the four warm-sensitive neurons tested lost either their osmosensitivity or thermosensitivity during synaptic blockade, and were taken to possess an inherent sensitivity to both temperature and osmolality. The phenomenon of reduced evaporative heat loss in dehydrated mammals may be explained, at least in part, by the reduced activity of MPO warm-sensitive neurons in a hyperosmotic environment.     

Temperature effects on neuronal membrane potentials and inward currents in rat hypothalamic tissue slices

Preoptic–anterior hypothalamic (PO/AH) neurones sense and regulate body temperature. Although controversial, it has been postulated that warm-induced depolarization determines neuronal thermosensitivity. Supporting this hypothesis, recent studies suggest that temperature-sensitive cationic channels (e.g. vanilloid receptor TRP channels) constitute the underlying mechanism of neuronal thermosensitivity. Moreover, earlier studies indicated that PO/AH neuronal warm sensitivity is due to depolarizing sodium currents that are sensitive to tetrodotoxin (TTX). To test these possibilities, intracellular recordings were made in rat hypothalamic tissue slices. Thermal effects on membrane potentials and currents were compared in PO/AH warm-sensitive, temperature-insensitive and silent neurones. All three types of neurones displayed slight depolarization during warming and hyperpolarization during cooling. There were no significant differences in membrane potential thermosensitivity for the different neuronal types. Voltage clamp recordings (at −92 mV) measured the thermal effects on persistent inward cationic currents. In all neurones, resting holding currents decreased during cooling and increased during warming, and there was no correlation between firing rate thermosensitivity and current thermosensitivity. To determine the thermosensitive contribution of persistent, TTX-sensitive currents, voltage clamp recordings were conducted in the presence of 0.5 μ m TTX. TTX decreased the current thermosensitivity in most neurones, but there were no resulting differences between the different neuronal types. The present study found no evidence of a resting ionic current that is unique to warm-sensitive neurones. This supports studies suggesting that neuronal thermosensitivity is controlled, not by resting currents, but rather by currents that determine rapid changes in membrane potential between successive action potentials.     

Peripheral nerve activity in response to heating the cat's skin

1. The sensitivity of the cat hind-limb skin to non-noxious heating was studied. Neural activity was recorded with micro-electrodes from intact multifibre fascicles of the saphenous nerve while the skin was actively heated or passively cooled.2. Moderate warming from indifferent temperatures of 30-34 degrees C to temperatures of 38-39 degrees C produced a reduction in the total rate of firing of the integrated discharge. Firing picked up sharply again at skin temperatures above 39 degrees C. A considerable fraction of the impulse activity elicited above 39 degrees C was carried by C-fibre afferents.3. Prolonged heating to temperatures in excess of 45 degrees C rendered the skin insensitive to further non-noxious heating or to touch.4. The neural response to a step increase in skin temperature consisted of a delayed overshoot and then a steady-state level of firing. Steady-state firing was proportional to the level of skin temperature.5. Nerves whose C-fibre input to the spinal cord had been selectively blocked showed a potentiation of the neural response to skin heating.6. The sensitivity of hind-limb skin to heating, as judged by the character of the multifibre discharge, appears similar to that reported for a highly warm-sensitive region of the nose.     

Intra-abdominal thermosensitivity in the rabbit as compared with spinal thermosensitivity

Summary In rabbits, intra-abdominal temperature sensors of the dorsal wall of the abdominal cavity were selectively stimulated by means of thermodes perfused with water of temperatures ranging from 12–50°C. Respiratory acceleration and vasodilatation of the skin could be elicited as thermoregulatory responses by intraabdominal warming. By intra-abdominal cooling a depression of an elevated respiratory frequency could be induced. This depressing effect was already fully developed at a perfusion temperature of 36°C and could not be further augmented by stronger cooling.Neural afferent activity recorded from filaments of the N. splanchnicus was found to increase with rising perfusion temperatures beginning with 36–37°C. It is concluded from these results that abdominal thermosensitivity is predominantly a warmth-sensitivity in contrast to spinal cord thermosensitivity which comprises both cold and warmth sensitivity.Heating intensities and heat inputs, respectively, of equally effective periods of spinal cord and intra-abdominal warming were compared with each other. It was found that heat input into the abdominal thermode had to be four times greater than that supplied to the vertebral canal thermode in order to evoke identical responses. Simultaneous application of equally effective thermal stimuli to the abdomen and the spinal cord reinforced the thermoregulatory responses.     

Temperature signals from skin and spinal cord converging on spinothalamic neurons

Summary In anesthetized, artificially ventilated cats with spinal transection at C₂, the temperature of the thoracolumbar spinal cord was varied by means of a water perfused thermode located in the peridural space of the vertebral canal. Single unit activity was recorded from the anterolateral tracts at C₃–C₅. As in a preceding investigation, units were found which were activated either by spinal cord cooling (spinal cold units) or by spinal cord heating (spinal warm units).In addition, the temperature of the skin of the trunk and the hind legs was varied by means of a water perfused coat in order to find out, whether spinal cold and warm units were also influenced by the signals of the cutaneous thermoreceptors. 11 spinal cold units and 10 spinal warm units were investigated in this way. With only one exception, they were found to be influenced by the skin temperature variations.Skin cooling below 38°C led to an increase of activity in 9 investigated spinal cold units. Skin cooling in 8 spinal warm units had, on the average, a negligible effect, although in some units a slight decrease of activity was observed.In several experiments the responses of spinal cold and warm units to skin heating above 40°C were investigated. 4 spinal cold units tested in this way responded to skin heating with an increase of activity. In 9 spinal warm units, activity was either depressed or increased by skin heating; one unit remained unaffected.