The thermoresponsiveness of ventromedial hypothalamic (VMH) neurons following repeated scrotal thermal stimulation of rats maintained at normothermic or acutely hypothermic core temperatures

Neurons within the central nervous system, including those within the ventromedial hypothalamic (VMH) nucleus, alter their neuronal activity in response to scrotal thermal stimulation. This study set out to establish if the thermoresponsiveness of VMH neurons becomes modified to repeated trials of scrotal thermal stimulation. VMH extracellular activity was recorded with a glass micropipette filled with 0.5 M sodium acetate in urethane-anaesthetized male Sprague-Dawley rats following 20 min scrotal heating (scrotal packs, 2 × 2 cm. filled with 40°C hot water) and scrotal cooling (scrotal packs filled with ice). In study A, VMH neurons were tested to 2 trials of scrotal heating and cooling with colonic temperatures (T_cs) servo-controlled at 37°C during both trials. In study B, VMH neurons were tested for 3 trials of scrotal thermal stimulation, with T_cs servo-controlled at 37, 35 and 33°C during the 3 trials. In study A, 42 VMH neurons were isolated. Based on their thermal coefficients (TCs) to the 1st trial of scrotal heating and cooling, 12 VMH neurons were classified as warm-responsive neurons (WRNs), 10 as cold-responsive neurons (CRNs) and 20 were temperature-non-responsive neurons (TNRNs). Of the neurons recorded long enough to test their thermoresponsiveness to 2nd trial of scrotal thermal stimulation (9 out of 12 WRNs, 7 out of 10 CRNs and 18 out of 20 TNRNs), the mean TCs of each type of VMH neuron did not significantly change between the 2 trials. In study B, 65 VMH neurons were isolated and 11 out of 22 WRNs, 7 out of 13 CRNs and 15 out of 30 TNRNs had their thermoresponsiveness tested to 3 trials of scrotal heating and cooling, with T_cs kept at 37, 35 and 33°C, respectively, for these trials. The mean TCs for VMH WRNs, CRNs and TNRNs again did not change between the 3 trials of scrotal thermal stimulation. However, mean basal firing rates did increase significantly of all recorded VMH neurons between the 1st and 3rd trials of scrotal heating and cooling as T_cs were acutely lowered from 37 to 33°C. Results demonstrated that VMH thermoresponsive neurons retain their responsiveness to repeated trials of scrotal heating and cooling of animals maintained at normothermic (37°C) or acutely hypothermic (35) and 33°C) temperatures.     

Difference in brown adipose tissue effector response and associated thermoresponsiveness of ventromedial hypothalamic (VMH) neurons of 21°C vs. 4°C acclimatized rats to scrotal thermal stimulation

The present study was designed (1) to determine if scrotal thermal stimulation would activate brown adipose tissue (BAT) thermogenesis, indicated by increases in interscapular BAT temperature (T_IBAT) of cold acclimatized (CA, kept at 4°C for 4 weeks) and room temperature acclimatized rats (RA, kept at 21°C for 4 weeks) and (2) to compare the thermoresponsiveness of VMH neurons of both groups to scrotal heating and cooling. VMH extracellular activity was recorded in male RA and CA Sprague-Dawley rats when scrotal temperatures (T_sc) were changed between 5–40°C via localized thermode (3 mm²) along with measurements of T_scs and T_IBATs. The CA-group showed significant increases in T_IBATs during scrotal cooling compared to respective T_IBATs of the RA-group. The ratio of VMH warm responsive (WRN), cold responsive (CRN) and temperature non-responsive (TNRN) neurons in the CA-group changed compared to that in the RA-group as a greater percentage of CRNs occurred in the CA-group. Also, the thermoresponsiveness of individual VMH CRNs of the CA rats was significantly increased compared to VMH CRNs of the RA-group. The results indicated that localized scrotal cooling of CA-rats (not RA-rats) can activate BAT thermogenesis. Furthermore, VMH CRNs increased their thermoresponsiveness with chronic cold exposure which may be an important neuronal adaptive response for the subsequent enhanced BAT thermogenic effector response seen in that group.     

Cholinergic stimulation in the posterior hypothalamic nucleus activates angiotensin II-sensitive neurons in the anterior hypothalamic area of rats

We have previously reported that some neurons in the anterior hypothalamic area (AHA) are tonically activated by endogenous angiotensins in rats and that activities of these AHA angiotensin II-sensitive neurons are enhanced in spontaneously hypertensive rats (SHR). Acetylcholine in the posterior hypothalamic nucleus (PHN) has been implicated in hypertension in SHR. It is suggested that there exist neuronal projections from the PHN to the AHA in rats. In this study, we examined whether cholinergic stimulation in the PHN activates AHA angiotensin II-sensitive neurons. Male Wistar rats were anesthetized and artificially ventilated. Extracellular potentials were recorded from single neurons in the AHA. Microinjection of carbachol, physostigmine and glutamate into the PHN caused an increase in firing rate of AHA angiotensin II-sensitive neurons in anesthetized rats. The carbachol-induced increase of firing rate was inhibited by pressure application of the AT1 receptor antagonist losartan onto AHA angiotensin II-sensitive neurons. The glutamate-induced increase of firing rate was also inhibited by the pressure application of losartan. PHN microinjections of carbachol and glutamate did not affect blood pressure in these anesthetized rats. In conscious rats, PHN microinjection of carbachol produced an increase of blood pressure and the carbachol-induced pressor response was inhibited by bilateral microinjections of losartan into the AHA. These findings indicate that cholinergic stimulation in the PHN activates AHA angiotensin II-sensitive neurons. It seems likely that the activation of AHA angiotensin II-sensitive neurons induced by PHN cholinergic stimulation is partly mediated via release of angiotensins at AHA angiotensin II-sensitive neuron levels.     

A functional medial preoptic nucleus (MPO) is required for scrotal thermal stimuli to alter the neuronal activity of thermoresponsive ventromedial hypothalamic (VMH) neurons

Thermoresponsiveness of ventromedial hypothalamic (VMH) neurons to scrotal thermal stimulation was determined before and after microinjection of lidocaine into the medial preoptic nucleus (MPO). Male, urethane anesthetized Sprague-Dawley rats, maintained colonically at 37 °C had VMH extracellular neuronal activity recorded following 3 cycles of scrotal thermal stimulation (localized, incremental heating and cooling, between 10 and 40 °C). Based on their thermal coefficients (TC), warm (WRN), cold (CRN) thermoresponsive and temperature non-responsive (TNRN) VMH neurons had their neuronal activity recorded following each cycle of scrotal thermal stimulation before and after MPO injections of sterile saline (300 nl volume) or 2% buffered lidocaine (200 ng). Thermoresponsiveness of all warm and cold VMH neurons to scrotal thermal stimulation was blocked by prior lidocaine administration into the MPO, effects that were reversed ~ 60 min after. However, MPO lidocaine administration caused no significant change in the thermal coefficients of VMH TNRNs to scrotal thermal stimulation. Results infer that a functional MPO is required for thermal afferent signals arising from the scrotum to reach thermoresponsive VMH neurons.     

Antidromic identification of neurons in the ventrolateral part of the medulla oblongata with ascending projections to the preoptic and anterior hypothalamic area (POA/AHA)

Seventy neurons in the ventrolateral medulla oblongata were antidromically activated by electrical stimulation of the preoptic and anterior hypothalamic area (POA/AHA) in female rats under urethane anesthesia. These identified cells were located within and adjacent to the nucleus reticularis lateralis and could be readily distinguished into at least two types of neurons, designated as ‘fast’ and ‘slow’ cells, on the basis of their waveform and conduction velocity.     

Intrascapular brown adipose tissue (IBAT) temperature and blood flow responses following ventromedial hypothalamic stimulation to sham and IBAT-denervated rats

Intrascapular brown adipose tissue temperature (T_IBAT) and capillary blood flow along with colonic (T_c) and tail (T_t) temperatures as well as blood pressure and heart rate responses were measured simultaneously in groups of age-natched, anesthetised, sham control and IBAT-denervated Long-Evans rats following VNH electrical stimulation. Unilateral VMH electrical stimulation (0.5 ms pulses of 100 μA at 50 Hz for 30 s) evoked rises in T_IBAT (above core) and IBAT blood flow in the Long-Evans sham control group, along with increases in blood pressure and heart rate. Rises in IBAT temperature and capillary blood flow were absent in the surgical denervated group following VMH electrical stimulation whereas the evoked pressor and tachycardic responses were left intact and were similar to those responses seen in the sham control group. The results indicate that acute bilateral sectioning of the IBAT intercostal nerves blocks the IBAT temperature and capillary blood flow increases evoked by VMH electrical stimulation.     

Hereditary motor and sensory neuropathy with absence of large myelinated fibers due to absence of large neurons in dorsal root ganglia and anterior horns, clinically associated with deafness, mental retardation, and epilepsy (HMSN-ADM)

Hereditary motor and sensory neuropathy (HMSN) with autosomal recessive inheritance represents a genetically heterogeneous group of disorders with variable clinical, pathologic and electrophysiologic manifestations. A new variant of autosomal recessive HMSN, clinically defined by sensorimotor polyneuropathy associated with deafness and mental retardation, has recently been described. We report on the first autopsy case with this type of HMSN: a girl of non-consanguineous parents with a presumably autosomal recessive type of motor and sensory neuropathy clinically associated with deafness, mental retardation, and epilepsy. The autopsy showed complete absence of large myelinated fibers in peripheral motor and sensory nerves corresponding to a lack of large neurons in dorsal root ganglia and anterior horns of the spinal cord, moderate neurogenic muscle atrophy, and nearly complete absence of neurons in the dentate nucleus of the cerebellum. Molecular genetic analyses in our case revealed neither genetic alterations in the survival motor neuron gene nor in the PMP-22 gene.