Cerebral metabolism of oxidized ascorbate

The brain has a high level of ascorbic acid which is thought to act as a reducing agent, e.g. in protecting tissues against oxidative stress. The mechanisms by which ascorbate is maintained in the useful, reduced state in the CNS is evaluated herein. Cerebrum from rat or calf was minced and homogenized in buffer. The endogenous levels of ascorbic acid, dehydro-l-ascorbic acid (DHAA) and reduced glutathione (GSH) were determined by HPLC with coulometric electrochemical detection. We also quantitated tissue capacity to regenerate ascorbic acid from DHAA, which is a product of electron transfer reactions of ascorbic acid. The homogenate was fractionated by centrifugation in steps up to110,000 × g and dialyzed free of low molecular weight components. The activity for reducing DHAA was approximately equal in the various supernatants; resuspended pellets had little activity. The active component has several properties of a protein, including being precipitated by solid ammonium sulfate addition to the tissue extract; most activity appeared in the 40–80% saturated fraction. The activity was stable up to a temperature of 80°C, but was lost at 95°C. The protein was digested by trypsin. The results suggest that a cytosolic component of cerebrum regenerates ascorbic acid in a step that preferentially uses GSH and NADPH as reducing cofactors. At least one form of DHAA reductase exists in brain.     

ACh and 5-HT stimulated thermogenesis at different core temperatures in the He-Cold hypothermie hamster

Hamsters in deep experimentally induced hypothermia, at body temperatures between 7°C and 11.5°C, were microinjected with 5-HT and ACh at brain sites in the anterior-preoptic area of the hypothalamus (AH/POA). ACh or 5-HT was injected into an AH/POA site at different starting core temperatures in different groups of hypothermic hamsters. Colonic temperatures (Tc) were maintained, following He-Cold induction, in a temperature controlled environmental chamber and measured with a YSI thermister probe and YSI tele-thermometer. Injections of either 5-HT or ACh at Tc's between 7.0°C and 9.0°C elicited only modest increases in Tc i.e., 0.3°C–0.6°C, respectively. As Tc increased, however, to ranges between 9.1°C–10.0°C and in different animals to greater than 10°C both ACh and 5-HT at the same sites elicited significant increases in Tc, 1.5°C for 5-HT and 2.2°C for ACh compared to saline injections. These data suggest that at the lowest Tc's we are observing a “cold block” of temperature sensitive sites in the AH/POA. Increasing the starting Tc beyond 9.0°C however, evokes significant increases in heat-gain following AH/POA injection of either ACh or 5-HT. These data are consistent with Myers' observations concerning the organization of heat-gain mechanisms at AH/POA sites. In addition, they suggest that both the afferent limb of the heat-gain circuit (5-HT) and the efferent limb of the circuit (ACh) are functionally impaired when Tc is close to the physiological limit in the He-Cold hypothermic hamster.     

Pyrogenic responses in the decerebrate monkey (Macaca cyclopis)

Pyrogenic responses to intravenous injections of typhoid vaccine were studied in intact and acute high- and low-level decerebrate monkeys (Macaca cyclopis). Responses in intact animals were characterized by drowsiness, increasing rectal and decreasing cutaneous temperatures of soles of the feet. Piloerection and shivering occurred after a latency of 30 min. Febrile responses of 2.3 ± 0.5°C peaked at 2 h. Soon after piloerection and shivering decreased and temperature of the soles stabilized. Body temperature returned to normal by 6 h. Side reactions of retching, vomiting, defecation, and urination were frequently noted. High-decerebrate preparations (brain stem truncated in the mesencephalon) showed no pyrogenic responses but urinated and defecated. Low-level preparations (truncated just rostral to the trapezoid body) showed all pyrogenic responses noted in intact animals, except drowsiness. Shivering and all side reactions were more marked than in intact animals. Latencies for onset of febrile response, maximum response, and defervescence were quite similar. Low-decerebrate animals showed a febrile peak of 1.6 to 2.3°C irrespective of “set point” for thermal regulation (animals regulating at 37.9 ± 0.3°C peaked at 1.9 ± 0.3°C; at 35.8 ± 0.2°C peaked at 2.2 ± 0.1°C; at 39.5°C peaked at 2.1°C). Febrile responses to bacterial pyrogens are not dependent on integrity of the hypothalamus and high-decerebrate preparations fail to show febrile responses because thermoregulatory heat gain mechanisms are tonically inhibited by released mesencephalic and rostral pontine tegmental systems. Lowering the decerebration to the level of the trapezoid body abolished released inhibition and restored thermoregulatory responses to cooling and febrile reactions to bacterial pyrogens.     

Thermoresponsiveness of posterior hypothalamic (PH) neurons of rats to scrotal and abdominal thermal stimulation

The thermoresponsiveness of posterior hypothalamic (PH) neurons to localized, incremental thermal heating and cooling between 10–40°C of the abdomen or scrotum was determined in urethane anesthetized, male Sprague–Dawley rats whose core temperature was maintained at 37°C during testing. PH extracellular neuronal activity was recorded along with changes in gastrocnemius muscle EMG activity and temperature (T_ms, indicative of shivering thermogenesis) and intrascapular brown adipose tissue temperature (T_IBATs, indicative of non-shivering thermogenesis). Seventy-five PH neurons were recorded following both scrotal and abdominal trials of thermal stimulation. Nine percent of PH neurons were classified as warm responsive neurons (WRNs), 20% as cold responsive (CRNs), and 71% as temperature nonresponsive neurons (TNRNs), based on their thermal coefficients (TCs). Mean TC for warm PH neurons was significantly increased with scrotal warming between 30–40°C from the mean TC of the same PH WRNs following abdominal warming. Similarly, the thermal coefficient was increased (i.e., was more negative) for cold responsive PH neurons to scrotal cooling (20–10°C) as opposed to the TC of the same PH CRNs for abdominal cooling. No shivering thermogenesis (no change in temperature or EMG activity from gastrocnemius muscle) or non-shivering thermogenesis (no significant increase in IBAT temperatures) occurred with scrotal or abdominal cooling in these 21°C acclimatized rats. The results indicate that a small population of PH neurons are thermoresponsive to localized physiological changes in temperature of the scrotum and abdomen with greater thermoresponsiveness shown of both warm and cold PH neurons to scrotal vs. abdominal thermal stimulation.     

Release of angiotensinogen by rat brain in vitro

The possibility that angiotensinogen is synthesized within the central nervous system was examined by incubating homogenates of rat brain in vitro. When the homogenates (100 mg wet weight/ml incubation medium) were incubated at 37 °C for 3 h, angiotensinogen concentration in the medium increased from 1.08 ± 0.07ng AI/ml (mean)±S.E.M. to 3.60 ± 0.16ng AI/ml; when incubated at 4 °C there was no significant change. This increase in angiotensinogen concentration was not depressed by actinomycin D (10 μg/ml, puromycin (5 μg/ml) or cycloheximide (10 μg/ml) although the latter two inhibitors of protein synthesis decreased the incorporation of [³H]leucine into protein by more than 97%. Furthermore, disruption of vesicles by sonication did not increase the angiotensinogen concentration of homogenates kept at 4 °C. These data suggest that the increase in the concentration of angiotensinogen during the 3 h incubation period is unlikely to represent secretion of stored angiotensinogen or newly synthesized protein but may represent conversion from a precursor molecule.The brain and cervical spinal cord were divided into 6 areas, homogenized and paired samples incubated for 2 h at 37 °C or 4 °C. At 4 °C, the concentration of angiotensinogen varied between regions, with higher concentrations in brain stem areas. For all 6 areas, concentrations were higher in samples incubated at 37 °C. Taking the difference in concentration for the two temperatures as an index of angiotensinogen release, regional differences were found with the highest value for pons/-midbrain/diencephalon and progressively lower values for medulla oblongata, cerebellum, cerebrum and cervical spinal cord. It is concluded that all regions of the brain as well as the cervical spinal cord release angiotensinogen in vitro and that this capacity is topographically distributed. However, it is still not certain that angiotensinogen released in vitro is synthesized in the CNS.     

Effect of 2450 MHz microwave energy on the blood—brain barrier to hydrophilic molecules. A. Effect on the permeability to sodium fluorescein

Significantly elevated levels of sodium fluorescein (MW 376) were found only in the brains of conscious rats made considerably hyperthermic (colonic temperatures > 41.0°C) by exposure to ambient heat (42 ± 2 °C) for 90 min or 2450 MHz CW microwave energy at 65 mW/cm² (SAR 13.0 W/kg) for 30 or 90 min. For microwave-exposed rats, fluorescein levels within the cortex and hypothalamus appeared to increase with increasing duration of exposure. This trend was not apparent in the cerebellum or medulla. Exposure to ambient heat resulted in increased fluorescein with the cortex, hypothalamus and medulla, but not the cerebellum, and, in general, ambient heat was not as effective as microwave energy in raising tracer concentrations within the brain. By far the greatest elevation of fluorescein dye in the brain occurred in those animals whose blood-brain barrier had been opened osmotically by intracarotid injection of 10 M urea. It is suggested that increased levels of sodium fluorescein found in the brain tissue of ambient heat and microwave-exposed rats most likely represent technically derived artifact and not a breakdown of the blood-brain barrier.     

Temperature regulation and dopaminergic systems in the brain: Does the substantia nigra play a role?

Male Sprague-Dawley rats (250–300 g) were stereotaxically implanted above the substantia nigra (SN) and preoptic/anterior hypothalamus (PO/AH) with 23 gauge stainless-steel guide tubes. Microinjections of apomorphine (APO), pimozide, or 0.9% saline were made bilaterally in 0.5 or 1.0 μl vols. using a Harvard infusion pump. Oxygen consumption, and colonic (T_c), tail-skin, and ambient temperatures were monitored each minute. Microinjections of APO into the SN produced a dose-dependent hypothermia that was antagonized by the central (1.0 μg) or systemic (0.5 mg/kg i.p.) injection of pimozide. This hypothermia was associated with increased heat loss and decreased heat production and occurred at ambient temperatures of 15, 23 and 35°C indicating that APO did not produce a poikilothermic state. Injecting 20 μg APO into the PO/AH or SN produced similar hypothermic responses; T_c fell 0.87± 0.10°C and1.02 ± 0.08°C, respectively. Pimozide injected into the SN failed to alter thermoregulation during exercise or exogenous heating. Moreover, systemic injections of APO before and after electrolytic lesioning of the SN produced similar hypothermic responses. However, when the SN was lesioned, (a) resting T_c was significantly reduced, and (b) during exposure to a 35°C environment for 55 min, T_c lose to39.5 ± 0.68°C before the lesion compared with a rise to only38.5 ± 0.13°C after the lesion. We conclude that the pharmacological data implicate a thermoregulatory role for dopamine receptors in the SN of the rat, but the functional significance of this central location in temperature regulation remains to be elucidated.     

Thermoregulatory effects of centrally administered bombesin, bradykinin, and methionine-enkephalin

Bombesin (BO, 100 ng), bradykinin (BR, 10 μg), or methionine-enkephalin (EN, 10 μg) was administered intracerebroventricularly to adult male rats at an environmental temperature of 4°C, 22°C, or 35°C, and rectal (T_re) and tail-skin (T_sk) temperatures were monitored for 5 hours. At 4°C and 22°C BO-treated animals developed acute hypothermia (max ΔT_re = −3.25°Cand −2.71°C, respectively) which persisted for 2 hours (p<0.05). At 22°C and at 300 min post-injection, BO-treated animals became significantly (p<0.05) hyperthermic (ΔT_re = +1.28°C) when compared to controls. While BR had no effects at 22°C, EN-injected rats demonstrated a significant (p<0.05) hyperthermia from 180 min through 300 min (ΔT_re = +1.40°C). At 22°C both BO and, surprisingly, EN increased T_re (e.g. ΔT_re = +3.49°Cand +2.01°C at 60 min). At 35°C EN elicited hyperthermia which was significantly (p<0.05) increased from time 0 at all sampling times (mean ΔT_re = +1.85°C) and from control levels at 300 min (ΔT_re = +1.07°C, p<0.05). BO again caused a significant (p<0.05, BO vs control, 30 min) decrement (ΔT_re = −1.22°C followed by increments (p<0.05) from 120–300 min. We conclude that the hypothermic effect of BO is dependent upon environmental temperature, partially caused by vasodilation, and possibly biphasic in nature; EN treatment generally elicits hyperthermia under these conditions while BR produced no effects on thermoregulation.     

Psychophysical detection and pain ratings of incremental thermal stimuli: A comparison with nociceptor responses in humans

The capacity of humans to detect and scale the magnitude of pain elicited by small increments in temperature, delivered by a contact thermal stimulator to localized areas of the arm or leg, was measured on non-painful and painful adaption temperatures. Subjects continuously rated the magnitude of any pain sensation elicited by heat increments superimposed on base temperatures of 38, 44, 47 or 48 °C. Detection threshold was also measured using a two-alternative forced choice method. The increment detection thresholds were lower for a continuously painful base of 47 °C than for a non-painful base of 38 °C in normal skin, and likewise were lower for a base of 38 °C following hyperalgesia induced by a mild burn. Incremental pain thresholds were nearly equal to detection thresholds on the base of 47 °C. The sensitivity with which subjects could scale the magnitude of pain was 2–7 times better for increments delivered on a 48 °C as opposed to a 38 °C base.Evoked responses in 6 single C-fiber mechanoheat nociceptive afferents (CMHs) were recorded percutaneously from the peroneal nerves of 3 humans, who were simultaneously judging pain magnitude. For a base of 38 °C, both the pain and the neural response thresholds were an order of magnitude higher than corresponding thresholds on a base of 48 °C. For a base of 47 °C, response thresholds of the CMHs ranged from 0.1 to 0.5 °C and were comparable to detection thresholds of 0.1 to 0.3 °C. The sensitivity with which most nociceptors could signal increment size was 3–4 times better on a 48 °C than a 38 °C base.Incremental pain sensitivity was not altered by a compression block of activity in myelinated afferents that eliminated the sense of cool and touch. Thus, activity in unmyelinated fibers alone could account for the sensitivity to incremental thermal stimuli that were superimposed on a painful base temperature. Further, it is likely that CMH nociceptors alone could provide the peripheral information necessary to detect and to make magnitude judgments of pain elicited by these stimuli.     

Hyperthermia induced by pre-pontine knife-cut: Evidence for a tonic inhibition of non-shivering thermogenesis in anaesthetized rat

Temperature of colon, interscapular brown adipose tissue (IBAT) and paw skin (index of vasomotor activity) were monitored before and after microwire knife lesions at the pre-pontine or/and the post-mammilary levels in the urethane-anaesthetized rats at room temperature of 23–24°C. Following the pre-pontine, but not the post-mammilary cut, colonic and IBAT temperatures increased by 3–4°C within 90–240 min. IBAT temperature rose faster with a shorter latency and attained a higher steady-state value than colonic temperature; skin temperature, however rose by only 0.8°C. A procaine microinjection into the pre-pontine area transiently increased by more than 1°C both colonic and IBAT temperatures, with similar kinetic as for the knife cut. Cardiac output distribution was measured using radiolabelled microspheres. Brown adipose tissue (BAT) was found to be the only organ to which the fractional blood flow increased dramatically (12 times over baseline value) during the development of hyperthermia. Propranolol, injected after the hyperthermia had fully developed, decreased IBAT and then colonic temperatures. Hexamethonium decreased both colonic and IBAT temperatures with a concomitant rise in skin temperature while tubocurarine was without effect. It is concluded that the hyperthermia observed after the pre-pontine lesion results from an increased sympathetic stimulation of BAT thermogenesis triggered by the release of a tonic inhibitory control on its heat production. Such an inhibitory system would be located somewhere between the lower midbrain and the upper pons.     

Vasopressin and the regulation of evaporative water loss and body temperature in the cat

The role of vasopressin as a possible mediator of the inhibition of evaporative water loss (EWL) in dehydrated, heat-stressed cats has been examined by intravenous (i.v.) and intracerebroventricular (i.c.v.) injections of arginine vasopressin (AVP). In normally hydrated cats exposed to an ambient temperature (Ta) of 38°C, neither EWL nor body temperature (Tb), measured in the hypothalamus, was significantly altered by i.v. AVP infusion. Measurements of plasma osmolality (pOsm), pAVP and cerebrospinal fluid AVP (csfAVP) were made normally hydrated cats at Tas of 25 and 38°C and after dehydration for 1–4 days at these temperatures. The relationship between pOsm and pAVP can be described equally well by either a linear model or a log-linear model (r = 0.81 for both models). The pOsm-csfAVP relationship is best described by alog-linear model (r = 0.80). A possible role for intracranially released AVP in ody temperature regulation and control of EWL was examined by injecting various doses of AVP into the lateral ventricles of normally hydrated cats. No effect of AVP injection on Tb was observed at either a Ta of 23°C or 38°C. EWL was also unaffected by i.c.v. AVP administration at a Ta of 38°C. To confirm futher that intracranial AVP is not responsible for elevation of Tb and reduction of EWL during dehydration and heat-stress, specific antiserum to AVP was injected into the ventricle of dehydrated animals at a Ta of 38°C. No sinificant effect on either Tb or EWL was measured subsequent to antiserum infusion. These negative findings indicate that AVP does not suppress EWL by either a peripheral or a central action and is therefore not responsible for lowered EWL and elevated Tb seen in dehydrated heat-stressed cats.     

Analysis of the thermolytic action of ICV neurotensin in the rat at different ambient temperatures

Intracerebroventricular (ICV) cannulae were implanted chronically in adult female Sprague Dawley rats for central injection of neurotensin (NT) or artificial CSP vehicle. During experiments carried out at 48 hr intervals, the body temperature of each rat was monitored continuously by a thermistor probe inserted in the colon. At an ambient temperature of 22°C, NT infused ICV in a threshold dose of 1.5 μg caused a mean maximum fall of 0.9°C in the rats' body temperature. This decline in core temperature was enhanced further to 1.4°C when the rats were exposed to an ambient temperature of 4°C for 1.0 hr immediately after the NT infusion. Similarly, when the rats were exposed to 34°, 36° or 40°C, again for 1.0 hr directly after NT administration, core temperature increased to a maximum of 0.3° to 0.6° during this interval. The maximum hyperthermic response following the control ICV infusion of CSF in rats exposed to the same elevated ambient temperatures was slightly greater (0.2–0.3°C) than that after infusion of NT, because of the initial thermolytic effect produced by the peptide. However, the respective slope of each rise in body temperature in both NT and CSF groups during exposure to all three warm temperatures was nevertheless identical. Overall, the results show that in the animal given NT centrally the core temperature tends to follow the ambient temperature, either cold or warm. Thus, it is concluded that NT possesses a clear-cut poikilothermic action on the central neutral systems underlying the control of body temperature. Therefore, it remains uncertain whether NT in fact could play any role in the mechanism within the diencephalon which mediates normal thermoregulatory function.     

Effect of 2450 MHz microwave energy on the blood-brain barrier to hydrophilic molecules. D. Brain temperature and blood-brain barrier permeability to hydrophilic tracers

Measurement of temperature within the cerebral cortex, hypothalamus, cerebellum and medulla of rats sham-, heat- or microwave-exposed revealed the presence of a thermal gradient within the brain. In all groups, cerebral cortex and the cerebellum were cooler than the deeper hypothalamus and medulla. Exposure to 2450 MHz CW microwaves or ambient heat (42 ± 2 °C) resulted in measurable elevation of regional brain temperature, but without alteration of temperature gradients normally observed within the brain. Exposure to 20 mW/cm² (SAR 4 W/kg) for 30, 90 or 180 min induced a small, but significantly (U = 0, ) increased temperature of thcolon, and in each region of the brain studied. Exposure to an incident power density of 65 mW/cm² (SAR 13.0 W/kg) for 30 or 90 min or to ambient heat (42 +- 2 °C) for 90 min resulted in a substantially greater thermal response as indicated by higher colonie and brain temperatures. Comparison of regional brain temperature with individual colonie temperatures is expressed as ΔT = t °C_brain − t °C_colon. In general ΔT values for ambient heat or microwaveexposed rats did not differ significantly from those of sham-exposed animals. Exposure to microwaves or ambient heat did not alter the general relationships between regional brain and colonie temperatures, i.e., cortical and cerebellar temperatures were always below and hypothalamic and medullary temperatures always above corresponding colonie temperatures.The plotted temperature data (brain vs colonie temperature) indicate a linear relationship between brain and colonie temperatures. Levels of sodium fluorescein (NAFl), horseradish peroxidase (HRP) and [¹⁴C]sucrose (described in preceding papers) within the brain show a high correlation (P < 0.05) with brain temperature. Suppression of blood-brain barrier permeability to hydrophilic tracers was most pronounced at brain temperatures exceeding ~40 °C and is demonstrated to be temperature dependent.     

Effect of climatic temperature on the age of onset of Huntington's chorea

The age of 1,403 subjects at onset of Huntington's chorea were drawn from the literature and related to the mean annual, January, and July temperatures of their place of residence. When the data were converted into mean annual, winter, and summer isotherms covering a range of 10° F (5·6° C), there was a statistically significant decrease in age of onset as the temperature increased. Over the ranges studied, winter temperatures exerted a stronger effect than summer temperatures. To reduce interference by ethnic factors, the analysis was repeated on North American subjects with similar results. It is suggested that repeated infections may provoke chorea and that the observed lowering of the age of onset is associated with increased susceptibility to infection on passing from cold to warm climates.     

Hypothermia inhibits ischemia-induced efflux of amino acids and neuronal damage in the hippocampus of aged rats

Brain hypothermia has been reported to protect against ischemic damages in adult animals. Our goal in this study was to examine whether brain hypothermia attenuates ischemic neuronal damages in the hippocampus of aged animals. We also determined effects of hypothermia on ischemia-induced releases of amino acids in the hippocampus. Temperature in the hippocampus of aged rats (19–23 months) was maintained at 36°C (normothermia), 33°C (mild hypothermia) or 30°C (moderately hypothermia) using a thermoregulator during 20 min of transient forebrain ischemia. Cerebral ischemia increased extracellular concentrations of glutamate and aspartate by 6- and 5-fold, respectively, in the normothermic group. Mild and moderate hypothermia, however, markedly inhibited the rise of these amino acids to less than 2-fold. Elevation of extracellular taurine, a putative inhibitory amino acid, was 16-fold in the normothermic rats. Mild hypothermia attenuated ischemia-induced increase in taurine (10-fold), and moderate hypothermia inhibited the increase. Ischemic damages, evaluated by histopathological grading of hippocampal CA1 area 7 days after ischemia, was significantly ameliorated in the mild (1.3±0.5, mean±S.E.M.) and moderate hypothermic rats (0.8±0.3) compared with the normothermic ones (3.4±0.4). These results suggest that brain hypothermia protects against ischemic neuronal damages even in the aged animals, and the protection is associated with inhibition of excessive effluxes of both excitatory and inhibitory amino acids.     

Suprachiasmatic nucleus: role in circannual body mass and hibernation rhythms of ground squirrels

Female golden-mantled ground squirrels that sustained complete ablation of the suprachiasmatic nucleus (SCNx) were housed pre- and post-operatively at 23°C and then at 6.5°C for 5–7 yr. SCNx and control animals held at the higher temperature manifested circannual rhythms (CARs) in body mass. In contrast, body mass CARs were not expressed in 50% of SCNx squirrels during cold exposure; rhythm amplitude was reduced to 25–40% of pre-operative values and the interval between successive peaks in body mass fell outside the circannual range. Unlike normal squirrels that hibernate for about 6 months during each circannual cycle, these SCNx squirrels expressed bouts of torpor nearly continuously throughout 2.5 yr of cold exposure. Body mass increases were often observed during hibernation—a phenomenon never observed in control animals. The remaining SCNx squirrels that did not hibernate continuously displayed CARs in body mass within the normal range. The effects of SCN ablation on body mass rhythms presumably are related to disrupted patterns of hibernation, food intake, and metabolism. The SCN, which sustains neural and metabolic activity at low tissue temperatures, may exert greater influence on thermoregulation and metabolism during the hibernation season than at other times of year, thereby accounting for the greater effect of SCN ablation in squirrels maintained at low ambient temperatures.     

Thermal dependence of chemosensory activity in the carotid body superfused in vitro

We studied the relationship between chemosensory activity and temperature in carotid bodies excised from pentobarbitone-anesthetized cats, and superfused in vitro at flows between 0.4 and 2.0 ml/min with modified Tyrode's solution buffered with HEPES at pH 7.43. The basal frequencies of chemosensory discharges were recorded from the entire carotid nerve at different steady thermal conditions. For preparations superfused with saline equilibrated with 100% O₂, thermally dependent increases in frequency were observed, with significant differences between all nearby thermal stages separated by 0.5°C steps between 36.0 and 38.5°C. The larger gains were recorded between higher temperatures at high flows, between mid temperatures at intermediate flows, and between lower temperatures at low flows. The critical temperature for the calculated maximal gain was directly correlated to superfusion flow. The basal frequencies were consistently elevated when switching to saline equilibrated with 20% O₂ and no significant differences in mean ranks were recorded between 36 and 37°C, as between 38 and 39°C, but frequencies at 36–37°C were significantly higher than those at 38–39°C. Brief rises in chemosensory discharges were evoked by injections of NaCN applied to carotid bodies superfused with saline equilibrated with 100% O₂. The least effective dose was lower at 40°C than at 37.5° or 35.0°C, but the reactivity and slope were not significantly different. It is concluded that the carotid body chemoreceptors fulfill the criteria for being considered as thermosensors, and that their frequency of discharges is thermally modulated within a range close to physiological body temperature.     

Response characteristics of specific thermoreceptive afferents innervating monkey facial skin and their relationship to human thermal sensitivity

The responses of thermoreceptive afferents to steady-state constant skin temperatures and temperature shifts were studied in rhesus monkeys by recording single fiber activity from fine dissected strands of the infraorbital nerve. Eighty-five warm and 134 cold fibers were identified by their specific sensitivity to warming and cooling of their receptive fields, which usually were restricted to single spots less than 1 mm in diameter. Warm fibers increased their firing rates with warming and decreased or ceased firing with cooling, while cold fibers showed an opposite behavior. Mean conduction velocity was 3.4 ± 1.7 m/s in warm fibers, and 9.0 ± 3.4 m/s in cold fibers.In response to constant skin temperatures in the innocuous temperature range below 43°C, warm fibers were active over the range of 30–42°C and showed maximum firing rates at 42°C. On the other hand, cold fibers were responsive to constant temperatures over the range of 20–42°C and their firing frequencies were maximal at 30°C and decreased as steady-state temperatures were raised or lowered. In addition, cold fibers exhibited periodic bursting activity when the temperature was below 35°C. The number of intraburst spikes in each burst increased as the constant temperature was     

Amiloride inhibition of chorda tympani responses to NaCI and its temperature dependency in mice

Inhibitory effects of amiloride on salt responses of the chorda tympani nerve and its temperature dependency were compared among three inbred strains of mice (C57BL, BALB and 129). In C57BL mice, lingual treatment with amiloride significantly suppressed responses to 0.1–1.0 M NaCI at two different temperatures, 24 ± 2°C and 12 ± 2°C. The magnitude of the amiloride-inhibited component of NaCl response was slightly larger at the higher temperature. In contrast, in BALB mice, amiloride suppression of NaCl responses was observed only at the lower temperature. No such suppression was exhibited by 129 mice at either temperature levels. These results suggest that there exist at least two different amiloride-sensitive receptor components for NaCl in mice: one is more sensitive to NaCl at the higher temperature, and the other is more sensitive at the lower temperature. It is hypothesized, C57BL mice possess the former (or both) component(s), whereas BALB mice have the latter one. The 129 strain may be lacking both components.