Toshikazu Kiyohara

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 rats 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.

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.

Convergence of thermal, osmotic and cardiovascular signals on preoptic and anterior hypothalamic neurons in the rat

Responsiveness of thermosensitive neurons in the preoptic and anterior hypothalamus (PO/AH) to osmotic and cardiovascular signals have been shown to be responsible, at least partly, for the reduced thermoregulation during dehydration and the hypothermia after acute blood loss. The responsiveness to local and peripheral (hepatoportal) osmotic stimuli were found in about 60% of PO/AH thermosensitive neurons and 12% of thermally insensitive neurons in tissue slices in vitro and in urethane-anesthetized rats. Since hyperosmotic stimuli predominantly decreased the activity of both warm-sensitive and cold-sensitive neurons, the reduced heat loss and heat production during dehydration may be explained by altered activity of PO/AH thermosensitive neurons induced by hyperosmolality. About 42% of 250 PO/AH neurons (66.3% of thermosensitive neurons and 30% of thermally insensitive neurons) exhibited the responsiveness to changes in blood pressure by less than 15 mmHg, which was found to be mediated by baro/volume receptors. Hypotensive stimuli predominantly increased the activity of warm-sensitive neurons and decreased the activity of cold-sensitive neurons. The neuronal responses may explain, at least in part, the hypothermia after acute bleeding.

Naloxone blocks the interferon-α induced changes in hypothalamic neuronal activity

Abstract The effects of recombinant human interferon-α (IFN-α) and naloxone (NLX) were studied on the single neuron activities of the preoptic and anterior hypothalamus (PO/AH) and the ventromedial hypothalamus (VMH) in tissue slices. Perfusion of IFN-α in physiological doses (10–5000 units/ml) decreased and increased the firing rate of the majority of PO/AH and VMH neurons respectively. The IFN-α-induced changes in firing rate of PO/AH and VMH neurons were reversibly blocked or attenuated by simultaneous application of NLX. The results suggest that IFN-α may exert its action through opiate receptors in the hypothalamus.

Responses of anterior hypothalamic-preoptic thermosensitive neurons to locally applied capsaicin

The effects of local application of capsaicin on the activity of single thermosensitive neurons in the anterior hypothalamic-preoptic area were studied in the urethane-anesthetized rat. Local injection of capsaicin through a cannula to the vicinity of the neurons increased the activity in 15 of 28 warm-units, decreased the activity in 2 of 4 cold-units and had no effect on 5 of 10 thermally-insensitive units. Electrophoretic application of capsaicin with the use of multibarrelled microelectrodes excited 16 of 27 warm-units, inhibited 12 of 17 cold-units and had no effect on 35 of 60 thermally-insensitive units. Progressive decreases in the responsiveness of the neurons to both capsaicin and the hypothalamic temperature were observed with repeated applications of capsaicin. Many neurons ceased firing after showing excitatory or inhibitory responses to single or repeated applications of capsaicin either by local injection or electrophoretic application. The results may explain the acute thermolytic response, as well as the subsequent decrease in responsiveness to the injection of capsaicin into the anterior hypothalamic-preoptic area, on the basis of changes in the activity of thermosensitive neurons in the anterior hypothalamic-preoptic area.

Responses of anterior hypothalamic-preoptic thermosensitive neurons to thyrotropin releasing hormone and cyclo(his-pro)

Effects of local application of thyrotropin releasing hormone (TRH) and its metabolite, histidyl-proline diketopiperazine [cyclo (His-Pro)], on the activity of thermosensitive and thermally-insensitive neurons of the anterior hypothalamic-preoptic area were investigated in urethane-anesthetized rats. Microelectrophoretic application of TRH changed the activity of 126 of 206 neurons tested. Thyrotropin releasing hormone predominantly decreased the activity of warm-sensitive neurons and increased the activity of cold-sensitive neurons. Since it has been generally assumed that warm-sensitive and cold-sensitive neurons in the anterior hypothalamic-preoptic area mediate heat and cold defence responses, respectively, the present results are consistent with previous findings showing hyperthermia after injection of TRH into the hypothalamus in the rat. Cyclo (His-Pro) affected the activity of 59 of 153 neurons tested. In addition, cyclo (His-Pro) did not preferentially affect warm- or cold-sensitive neurons. These results indicate that the previously-determined hypothermic effect of cyclo (His-Pro) cannot be explained by its effects on thermosensitive neurons in the anterior hypothalamic-preoptic area.

Activity of hypothalamic thermosensitive neurons during cortical spreading depression in the rat

Effects of single waves of cortical spreading depression (CSD) on unit activity of the ipsilateral preoptic and anterior hypothalamic (PO/AH) neurons were studied in urethane-anesthetized rats. When CSD entered the frontal cortex, the firing rate of the majority (85%, 22/26 units) of PO/AH warm-sensitive neurons decreased for 1.4-14.2 min and the remaining 4 neurons were unaffected. In contrast, 10 (77%) of the 13 cold-sensitive neurons increased their firing rates for 1.2-10.4 min after the CSD entrance of the frontal cortex. Of the remaining 3 neurons, two decreased their firing rates and one showed no change during CSD. Thirteen (76%) of the 17 thermally insensitive neurons were not affected by CSD, but the remaining 4 neurons decreased their firing rates slightly for about 1.4 min. The most critical cortical region responsible for the activity change of the PO/AH thermosensitive neurons during CSD was found to lie in the sulcal prefrontal cortex by observing the effect of a single CSD elicited separately from the occipital and the frontal cortex on the same PO/AH neurons (a double-CSD technique). The result, together with the previous ones on thermoregulatory responses during the frontal CSD, suggests that the sulcal prefrontal cortex exerts a tonic influence on the activity of the hypothalamic thermosensitive neurons and is involved in the central control of thermoregulation.

Responsiveness of monkey preoptic thermosensitive neurons to non-thermal emotional stimuli

Responsiveness of 143 preoptic neurons to changes in hypothalamic temperature and to non-thermal emotional stimuli were investigated while rewarding (foods) and aversive objects (hypertonic saline, a toy snake, an air puffer) were given. About 71% of thermosensitive neurons and 32% of thermally insensitive neurons changed the activity when emotional stimuli were shown to and/or tasted by the monkey. Such responses were modulated by satiety/hunger state and were dependent on the degree of perturbation of emotional state. About half of the neurons tested responded when the monkey opened the mouth and protruded the tongue or moved fingers in trying to obtain foods with strong motivation, but did not when the animal made such movements less readily or reluctantly with the progress of satiation. This response was most frequently found among warm-units. The results raise a possibility that preoptic thermosensitive neurons, besides their postulated thermoregulatory functions, might be involved in the response of coordination with thermal and non-thermal emotional behaviors controlled in the hypothalamus.

Responses of preoptic thermosensitive neurons to medial forebrain bundle stimulation

Single-unit responses of neurons in the preoptic and anterior hypothalamus (PO/AH) to local thermal stimulation and electrical stimulation of the medial forebrain bundle (MFB) were studied in urethane-anesthetized male rats. In a total of 286 units (112 warm-units, 37 cold-units and 137 thermally insensitive units), 109 units (49 warm-units, 13 cold-units and 47 thermally insensitive units) responded to single pulse stimulation of MFB. The units initially inhibited by MFB stimulation corresponded to 64.2% (70 of 109), the units with facilitatory responses were 27.5% (30 of 109) and the antidromically activated units were 8.3% (9 of 109). High incidence of inhibition by noradrenaline (NA) applied iontophoretically was observed in the neurons inhibited by the MFB stimulation. Iontophoretic application of dichloroisoproterenol to 2 warm-units blocked both the NA-induced inhibition and the MFB-induced inhibition. These ascending and descending connections of the MFB with PO/AH thermosensitive neurons may be part of the neural circuits responsible for thermoregulation.

Activity of thermosensitive neurons of monkey preoptic hypothalamus during thermoregulatory operant behavior

Unit activities of thermosensitive (TS) and non-TS neurons in the medial preoptic area (MPO) of the monkey were investigated during a high fixed-ratio (FR 12-30) bar press behavior to seek cool air (CT) in a warm environment. The monkey performed the task when ambient temperature (Ta) was raised (35-43 degrees C) and the animal was rewarded with a fall in Ta (23-25 degrees C). The population of neurons which changed the activity at least in one phase of CT was significantly higher among TS neurons (42 of 46) than among non-TS neurons (29 of 64). The most frequently observed responses were the sustained increase or decrease in activity during the bar press period and/or the cooling period. The bar press related activity was not a pure motor coupled response, but its magnitude was greatly modified by the strength of motivation of animals to seek cool air. The cooling phase-related activity was not a thermosensory response which simply reflects the level of skin temperature or its change. It was shown that the response was dependent upon the rewarding value of the cooling air. The results suggest that TS neurons in the MPO may be involved in the control of thermoregulatory cooling behavior.