Insensitive Neurons Research Articles

Internal and external information processing by lateral hypothalamic glucose-sensitive and insensitive neurons during bar press feeding in the monkey

Single neuron activities in the lateral hypothalamic area (LHA) were recorded during bar press feeding task in the monkey. First registered neurons were sorted into 2 groups, glucose-sensitive (GS) and glucose-insensitive (GIS) neurons, depending on their glucose sensitivity. Then firing variations to feeding, electrophoretically applied catecholamines and opiate, and to odor and taste stimuli were investigated. GS neurons responded to dopamine, noradrenaline and morphine more often than GIS neurons. In feeding task GS neurons responded during bar press (BP) and reward (RW) periods with long-lasting inhibition of firing and at cue tone (CT) with transient inhibition, while GIS neurons responded during BP and RW periods mainly with excitation and at cue light (CL) with excitation. A majority of GS neurons responded to both odor and taste stimuli more often than GIS neurons. Data suggest that these two kinds of neurons in the LHA may be involved in different functional aspects of feeding: GS neurons, mainly in internal information processing and reward mechanism, and GIS neurons, in external information processing and motor aspects.

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.

Neuronal sensitivities in preoptic tissue slices: Interactions among homeostatic systems

The preoptic area participates in many homeostatic systems, which include the regulation of body temperature, fluid and metabolite balance, and reproduction. Some preoptic neurons have been shown to be sensitive to either temperature, osmotic pressure, glucose, testosterone or estradiol. While previous studies have treated these as separate and distinct neuronal populations, this paper reviews recent experiments which show that many neurons have multiple sensitivities to these endogenous factors. Neurons in preoptic tissue slices were tested for their responses to changes in temperature, as well as various perfusion media containing 30 pg/ml testosterone or estradiol, low glucose (1.0 mM) or increased osmotic pressure (309 mosmol/kg). The steroid-sensitive, osmosensitive and glucosensitive neurons were not confined to the temperature insensitive neurons; but instead nearly half of the thermosensitive neurons responded to these nonthermal stimuli. In addition, many osmosensitive neurons showed glucosensitivity and steroid-sensitivity. This suggests that, even at the neuronal level, there is a basis for interactions between homeostatic systems.

Effects of interferon-α on the activity of preoptic thermosensitive neurons in tissue slices

Effects of recombinant interferon-α (IFN-α) on the single activity of thermosensitive and thermally insensitive neurons in the preoptic and anterior hypothalamus (PO/AH) were investigated in rat's brain tissue slices. IFN-α, in doses of less than 5 × 10 3 U/ml, decreased the activity in 34 of 52 warm-sensitive neurons and increased the activity in 3 of 5 cold-sensitive neurons, but had no effect on the majority (12 of 17) of thermally insensitive neurons. The neuronal responses to local IFN-α could be observed in a Ca 2+-free/high Mg 2+ solution, suggesting the direct action of IFN-α. The actions of IFN-α on thermosensitive neurons were blocked by concurrent application of naloxone, but not by sodium salicylate in doses which effectively blocked the neuronal responses to endotoxin and leukocytic pyrogen in the previous studies. The fever induced by IFN-α may be explained, at least partly, by the direct actions of IFN-α on the PO/AH thermosensitive neurons, which involve the opiate receptor mechanisms.

Effects of progesterone on thermosensitive neurons in preoptic slice preparations

Single neuronal activities in preoptic (PO) slice preparations from both male and female rats were recorded and examined for their responses to 3 ng/ml or 30 ng/ml progesterone (P). Of 31 warm-sensitive neurons, 19 (61.3%) were inhibited by P, 5 (16.1%) were excited, and 7 (22.6%) did not respond to P. Of 26 thermally insensitive neurons, 4 (15.4%) were inhibited by P, 3 (11.5%) were excited, and 19 (73.1%) did not respond to P. Of 4 cold-sensitive neurons, 3 were inhibited and one was excited. These results demonstrate that P inhibits most warm-sensitive neurons directly or indirectly via local neuronal circuits in the slice.

Effects of interleukin-1 and arachiodonate on the preoptic and anterior hypothalamic neurons

Effects of microelectrophoretic application of ultrapure human interleukin-1 (IL-1), an endogenous pyrogen, on the activity of 80 neurons in the preoptic and anterior hypothalamus (PO/AH) were investigated in the urethane anesthetized rat. IL-1 predominantly decreased the activity of warm-sensitive neurons (15 of 19) and increased the activity of cold-sensitive neurons (10 of 12), but had no effect on 37 of 49 thermally insensitive neurons. The neuronal responses to IL-1 were blocked or attenuated by concurrent application of mepacrine (a phospholipase inhibitor) or sodium salicylate (a cyclooxygenase inhibitor). Local application of sodium arachidonate decreased the activity in 17 of 28 warm-units and excited 12 of 16 cold-units, and the effects of arachidonate were blocked by sodium salicylate. The results are compatible with the view that one or more cyclooxygenase metabolites of arachiodonic acid are involved in the IL-1 induced fever.

Effect of PGE2 on preoptic and anterior hypothalamic neurons using brain slice preparation.

In the present study, effects of prostaglandin (PG) E2 on the hypothalamic neurons were investigated using slice preparations of rats. Warm- (57%) and cold-responsive (33.3%) and thermally insensitive (42.3%) neurons were facilitated by PGE applied in a culture chamber. Some neurons (5.1%) showed inhibitory response to PGE2. The remaining neurons did not show any responsiveness to PGE2. Moreover, we also examined the effects of PGE2 on the hypothalamic neurons both in normal Krebs-Ringer solution and synaptic blocking medium (low Ca2+, high Mg2+). Most of the neurons (12/15) retained their responsiveness to PGE2 in the synaptic blocking medium, indicating that PGE2 has a direct action on the hypothalamic neuron. Therefore, it is conceivable that neurons in the preoptic and anterior hypothalamic region that respond to PGE2 might play an important role in the development of fever. However, characteristics of neurons responding to PGE2 were not determined based on their thermoresponsiveness.

Effects of endogenous pyrogen and prostaglandin E2 on hypothalamic neurons in guinea pig brain slices

To investigate the direct effects of endogenous pyrogen (EP) and prostaglandin E2 (PGE2) on the activity of neurons in the preoptic and anterior hypothalamic (PO-AH) region, single-unit activity was recorded from brain tissue slices prepared from the PO-AH region of guinea pigs. When EP was applied into the perfusate 18% of warm-responsive neurons decreased their activity, and 23% of warm-responsive neurons increased their activity. Most of the thermally insensitive neurons did not respond to EP. PGE2 inhibited 29% of warm-responsive neurons and facilitated 15% of them. Moreover, when EP and PGE2 were applied to the same neurons at different times, the same directions of changes in neuronal activity were observed in 72% of total neurons examined. These results suggest that EP and PGE2 change the neuronal activity of the thermoresponsive neurons in the PO-AH region involved in fever induction. However, by these results, the direction of neuronal response induced by these substances could not be generally categorized based on the thermoresponsiveness of the individual neuron.

Convergence of hepatoportal osmotic and cardiovascular signals on preoptic thermosensitive neurons

Effects of hepatoportal osmotic stimuli and changes in arterial blood pressure were studied on the neuronal activity of 24 thermosensitive and 47 thermally insensitive neurons of the preoptic and anterior hypothalamus (PO/AH) in the urethane-anesthetized rat. Infusion of hypertonic (3% NaCl, 9% mannitol) or hypotonie (water) solutions into the hepatic portal vein changes the activity in 59% of thermosensitive neurons and 13% of thermally insensitive neurons but the injection into the femoral vein did not. Changes in blood pressure induced by intravenous injection of vasoactive drugs altered the activity of thermosensitive neurons (75%) and thermally insensitive neurons (32%). Neurons having dual sensitivity to both osmotic and blood pressure were more frequently found among thermosensitive neurons (10/24) than among thermally insensitive neurons (4/47), x 2( l)=11.03, p<0.001. The convergence of osmotic and baro/volaemic information on thermosensitive neurons may provide explanations for thermoregulatory changes observed during dehydration and acute hypotension.

Responses of preoptic thermosensitive neurons to changes in blood pressure

Effects of changes in arterial blood pressure were studied on the neuronal activity of 56 thermosensitive and 122 thermally insensitive neurons of the preoptic and anterior hypothalamus (PO/AH) in the urethane-anesthetized rat. Falls in blood pressure by 15 mmHg or less, which were induced by hemorrhage or by IV injection of vasoactive drug, resulted in the increased activity of warm-sensitive neurons (53.3%) and the decreased activity of cold-sensitive neurons (45.5%). However, the majority (71.3%) of thermally insensitive neurons were not affected by a rise or a fall in blood pressure by as large as 30 mmHg. Bilateral sections of glossopharyngeal, vagus and sympathetic nerves abolished the neuronal responses to blood pressure changes, indicating that the responses are mediated largely by peripheral baro/volume receptors. Increased and decreased activities of warm-sensitive neurons and cold-sensitive neurons during hypotension respectively suggest that at least a part of hypothermia observed during acute hemorrhage is a centrally induced response having a survival value.

Effects of endogenous pyrogen and prostaglandin E2 on hypothalamic neurons in rat brain slices.

We investigated the effects of endogenous pyrogen and prostaglandin E2 (PGE2) on the preoptic and anterior hypothalamic (POAH) neurons using brain slice preparations from the rat. Partially purified endogenous pyrogen did not change the activities of most of the neurons in the POAH region when applied locally through a micropipette attached to the recording electrode in proximity to the neurons. This indicates that partially purified endogenous pyrogen does not act directly on the neuronal activity in the POAH region. The partially purified endogenous pyrogen, applied into a culture chamber containing a brain slice, facilitated the activities in 24% of the total neurons tested, regardless of the thermal specificity of the neurons. Moreover, PGE2 added to the culture chamber facilitated 48% of the warm-responsive, 33% of the cold-responsive, and 29% of the thermally insensitive neurons. The direction of change in neuronal activity induced by partially purified endogenous pyrogen appears to be almost the same as that induced by PGE2 when these substances were applied by perfusion to the same neuron in the culture chamber. These results suggest that partially purified pyrogen applied to the perfusate of the culture chamber stimulates some constituents of brain tissue to synthesize and release prostaglandin, which in turn affects the neuronal activity of the POAH region.

Catecholaminergic mechanisms of feeding-related lateral hypothalamic activity in the monkey

The functional role of the catecholaminergic mechanism in the lateral hypothalamus (LHA), in feeding behavior of the monkey was investigated by single neuron activity recording and electrophoretic application of dopamine (DA), noradrenaline (NA) and their antagonists. The feeding paradigm had 4 phases: (1) cue light (CL) signaled start of bar press; (2) bar press (BP, 20–30 times); (3) short cue tone (CT) triggered by last bar press signaled presentation of food; and (4) ingestion-reward (RW). Of 312 neurons tested, 189 (61%) responded in one or more phases of the feeding task. Two types of response were observed: CL- or CT-related transient, and BP- or RW-related long-lasting responses. These feeding-related responses depended on the nature of the food and on the hunger-satiety level. DA excited or inhibited different neurons, while NA mainly inhibited firing. DA-sensitive neurons responded more often in the feeding task than insensitive neurons due mainly to differences in responsiveness to CL on (X 2test, P< 0.01), at motor initiation, and during BP (P < 0.05). Spiperone blocked the former two responses. NA-sensitive neurons responded more often in the feeding task due to responsiveness during BP and RW (P < 0.01). Sotalol blocked some BP-related responses, and phenoxybenzamine and sotalol blocked the CT-related responses. The data suggest that dopaminergic and noradrenergic inputs in the LHA are crucial in task initiation and reward processing, respectively. Integration oof these catecholaminergic and other inputs in the LHA might be important in accomplishing motivated feeding.

Effects of carbon dioxide on preoptic thermosensitive neurons in vitro

Effects of carbon dioxide (CO2) on the firing rates of preoptic thermosensitive neurons were examined in rat brain slice preparations. The perfusing medium was saturated with gas mixtures consisting of 90% O2 and one of various concentrations (5%, 6.3%, 7.5%, and 10%) of CO2 balanced with N2. The medium containing 5% CO2 was used as control. Most preoptic neurons were inhibited during application of a high CO2 medium. An excitatory effect of CO2 on a small number of neurons was also significant, although this was weak and transient compared to the inhibitory effect. Thermosensitivities of the neurons did not correlate with their CO2 sensitivities. The influence of CO2 tended to be more evident at higher temperatures. We conclude that the direct effect of CO2 on PO thermosensitive neurons as well as on thermally insensitive neurons is mainly inhibitory.

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.

Effects of carbon dioxide inhalation on preoptic thermosensitive neurons.

The effects of inspired CO2 on preoptic thermosensitive neurons were studied in urethanized rats. Most of the neurons changed their activities diversely while the rat breathed 4%, 7%, and 10% CO2 gas mixtures. Half of the neurons increased activity during CO2 inhalation, but activity was not necessarily intensified by elevating CO2 concentration. Thermosensitive neurons tended to increase activity more than thermally insensitive neurons. The effect of CO2 on sensitivity of thermosensitive neurons was also examined by regression of neuronal activity on preoptic temperature. The slopes of the regression lines during CO2 inhalation did not differ significantly from those during air inhalation in either warm-sensitive or cold-sensitive neurons, but CO2 did elevate the intercepts in most instances (P less than 0.01). However, if P less than 0.05 is accepted as a significance level, the slopes of the regression lines for warm-sensitive neurons tended to decrease during CO2 inhalation (9/39 pairs). The present results indicate that preoptic thermosensitive neurons generally increase their activities and modify their thermosensitivities during CO2 inhalation.

Maturation of opioid sensitivity of fetal mouse dorsal root ganglion neuron perikarya in organotypic cultures: Regulation by spinal cord

Opioid agonists selectively decrease the duration of the Ca 2+ component of the action potential recorded from embryonic dorsal root ganglion neurons in dissociated cell cultures. In contrast, no significant alterations in the action potentials generated by adult dorsal root ganglion neurons in vivo were detected during opioid exposure. In the present study, the perikaryal opioid sensitivity of fetal mouse dorsal root ganglion neurons was analyzed during maturation in organotypic explant cultures. To determine whether spinal cord might influence this sensitivity, neuron perikarya were tested in ganglia grown: (a) in isolation; (b) attached to spinal cord explants; and (c) attached to spinal cord, but decentralized by a dorsal root transection in mature explants 1–2 weeks before the tests. After 2–8 weeks in culture, the duration of the Ba 2+-enhanced Ca 2+ component of intracellularly recorded action potentials was measured prior to and during bath exposure to the opioid, [ d-Ala 2, d-Leu 5]enkephalin. Sensitive neurons were characterized by a marked, reversible reduction (averaging about 50%) in the duration of the Ca 2+ component (which was antagonized by naloxone). The fraction of opioid-sensitive neuron perikarya in dorsal root ganglia grown attached to cord explants was significantly lower (48%) than in ganglia grown isolated (78%) or decentralized in vitro (79%). The mean duration of the Ca 2+ component was significantly shorter in ganglion cells which had been grown attached to cord, or subsequently decentralized, compared to cells grown in isolated ganglia (by 24 and 38%, respectively). This difference was even larger in the opioid-insensitive groups. Although opioid-sensitive perikarya in ganglia grown attached to cord had a significantly longer Ba 2+-enhanced Ca 2+ component than that of insensitive neurons, some of the insensitive perikarya in all 3 types of explant paradigms displayed Ca 2+ components which were as prolonged as those of sensitive cells. The results obtained in this study support the hypothesis that the observed decrease in the fraction of opioid-sensitive perikarya during development of fetal mouse dorsal root ganglia is due to regulation by interactions with their central target tissue, the spinal cord. The developmental decrease in the duration of the Ca 2+ component of the action potential of these ganglion cells is also enhanced by the presence of the spinal cord. However, regulation of functional opiate receptors and Ca 2+ component duration of the ganglion cell perikarya appear to be independent processes.

The distribution of p-chlorophenylalanine insensitive serotonin neurons in the rat brain

The distribution of p-chlorophenylalanine insensitive serotonin neurons in the rat brain

Effects of endotoxin and sodium salicylate on the preoptic thermosensitive neurons in tissue slices

Effects of E. coli endotoxin and sodium salicylate (Sal) on single-unit activity of thermosensitive neurons recorded in slices of preoptic and anterior hypothalamic area (PO/AH) were studied in vitro. Perfusion of endotoxin-containing Krebs-Ringer's solution or local application of endotoxin in the immediate vicinity of recording neurons decreased and increased the firing rate of 31 of 34 warm-sensitive neurons and a cold-sensitive neuron, but had no effect on the majority of thermally insensitive neurons. In about half of warm-sensitive neurons the inhibitory response to endotoxin was preceded by a transient increase in firing rate. The pyrogen-induced decrease in firing rate in warm-sensitive neurons was reversibly blocked or attenuated by local application of Sal in a dose-dependent manner. The results are consistent with the view that pyrogen and Sal act in the PO/AH to produce fever and antipyresis, respectively, by appropriately offsetting the activity of thermosensitive neurons.

Two types of Ca currents in the sensory epithelium of the ampullary electro-receptor in [formula omitted

The functional role of the catecholaminergic mechanism in the lateral hypothalamus (LHA), in feeding behavior of the monkey was investigated by single neuron activity recording and electrophoretic application of dopamine (DA), noradrenaline (NA) and their antagonists. The feeding paradigm had 4 phases: (1) cue light (CL) signaled start of bar press; (2) bar press (BP, 20–30 times); (3) short cue tone (CT) triggered by last bar press signaled presentation of food; and (4) ingestion-reward (RW). Of 312 neurons tested, 189 (61%) responded in one or more phases of the feeding task. Two types of response were observed: CL- or CT-related transient, and BP- or RW-related long-lasting responses. These feeding-related responses depended on the nature of the food and on the hunger-satiety level. DA excited or inhibited different neurons, while NA mainly inhibited firing. DA-sensitive neurons responded more often in the feeding task than insensitive neurons due mainly to differences in responsiveness to CL on (X2test, P< 0.01), at motor initiation, and during BP (P < 0.05). Spiperone blocked the former two responses. NA-sensitive neurons responded more often in the feeding task due to responsiveness during BP and RW (P < 0.01). Sotalol blocked some BP-related responses, and phenoxybenzamine and sotalol blocked the CT-related responses. The data suggest that dopaminergic and noradrenergic inputs in the LHA are crucial in task initiation and reward processing, respectively. Integration oof these catecholaminergic and other inputs in the LHA might be important in accomplishing motivated feeding.

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.