Hypothalamic stimulation induces vagally mediated hypocalcemia in the rat

A hypothalamo-vagal mechanism of immobilization (IMB) stress-induced hypocalcemia was investigated in rats. Bilateral lesions in the Ventromedial nucleus of the hypothalamus (VMH), but not those of the lateral hypothalamic area (LHA) or the paraventricular nucleus (PVN), eliminated the calcium-lowering effect of IMB. None of these lesions, however, affected the basal levels of the blood calcium. An electrical stimulation of the VMH induced a significant decrease in the blood calcium level (0.07 mM fall) 60 min after stimulation. The hypocalcemic response was eliminated by a vagotomy of the gastric branches but not by that of the thyroid/parathyroid branches. These results suggest that the VMH mediates IMB-induced hypocalcemia through its influence on the gastric vagus.     

Hypothalamic substrates of self-stimulation in cats

The purpose of this study was to gather anatomical data concerning sites for self-stimulation in the lateral hypothalamus in the cat. The study was conducted on 25 adult cats. In each cat, one to three monopolar stimulating electrodes were implanted bilaterally in the lateral hypothalamus in a region between sections Fr 10.0 and Fr 13.0, L 2.0 and L 5.0, and H -2.0 and H -6.0. A reference electrode was placed in the calvaria over the frontal sinus. Twenty-two of these cats learned to press a lever when each press was rewarded by a brief (0.3 s) electrical stimulus (2.0 to 7.0 V, 100/s, 1 ms duration per pulse) delivered to the hypothalamus. Postmortem anatomical analysis of the brains revealed that most of the positive rewarding sites were located in a midlateral hypothalamic zone, which included the medial forebrain bundle, and were localized to section Fr 11.5, between L 2.0 and L. 5.0, and H -3.0 and H -5.5.     

Sympathoadrenal excitation and inhibition by lower brainstem stimulation in cats

Effects of stimulation of brainstem sites on hemodynamics and plasma catecholamine levels were assessed in cats under chloralose-urethane anesthesia. Pressor areas of the dorsal medulla (DM) and ventrolateral medulla (VLM) and the depressor area of the paramedian reticular nucleus (PRN) were stimulated electrically using a monopolar electrode, or chemically using sodium glutamate microinjection. Plasma levels of norepinephrine (NE) and epinephrine (EPI) were measured in caval blood above the adrenal veins. Electrical stimulation of the DM and VLM produced increases in blood pressure and in plasma NE and EPI levels that were enhanced after acute vagotomies. The NE and EPI responses were attenuated after acute, bilateral adrenalectomies, confirming augmented adrenomedullary secretion, whereas the pressor responses were intact. Injection of sodium glutamate into the same pressor regions of the DM or VLM also produced pressor responses and elevated plasma catecholamine levels, indicating that the responses resulted from activation of neuronal perikarya. Stimulation of the PRN attenuated pressor and catecholamine responses during stimulation of the DM and VLM. The results indicate that pressor responses during stimulation of the DM and VLM are due at least partly to activation of perikarya in these regions, are associated with but not dependent on adrenomedullary activation, and are enhanced after vagotomy; and that neurons of the PRN exert inhibitory modulation of the pressor and adrenomedullary responses during stimulation of VLM and DM.     

Dartos reflex: a sympathetically mediated scrotal reflex

The dartos muscle is a sympathetically innervated dermal muscle layer within the scrotum, distinct from the somatically innervated cremasteric muscle. We electrophysiologically demonstrate the presence of a dartos reflex (DR), which can be used to evaluate the thoracolumbar sympathetic and genitofemoral nerve pathways. In 20 healthy men, we evoked the DR by cutaneous stimulation of the thigh and recorded the resultant scrotal skin contraction. We recorded hand, foot, and perineal sympathetic skin responses (SSRs) as controls. The DR was reliable and reproducible, as were the SSRs. The mean left DR latency was 4.8 s (SD, 2.7 s) and right DR latency was 5.4 s (SD, 3 .4), both of which were longer than the mean hand, foot, and perineal SSRs (P < 0.05). An intact reflex arc reflects the integrity of the afferent and efferent branches of the genitofemoral nerve (T12-L2). The DR test can also be used to assess scrotal autonomic innervation. Abnormalities of dartos innervation may impact testis thermoregulation and spermatogenesis.     

Hypothalamic influences on the activity of superior colliculus neurons in cats

Experimens on immobilized unanesthetized cats showed that hypothalamic stimulation effectively modifies background and evoked activity of superior colliculus neurons. Some differences in the nature of influences from different hypothalamic areas were revealed. Stimulation of the AHA and HL often caused depression of the background impulsation with initial inhibition, especially during stimulation of HL. Cyclic modulation of background activity was also revealed. The influence of these structures on the activity evoked by light was mostly of modulating character. Stimulation of the ventromedial nucleus produced both inhibitory and excitatory effects on the activity of tectal neurons with a tendency to an increased rate of the latter when using repetitive stimulation.     

Unilateral pleasure-center stimulation in split-brain cats

Unilateral bipolar stimulation at seven positively reinforcing sites ranging from the ventral mesencephalic reticular formation to the preoptic region, in five split-brain cats, was shown to reinforce pattern discrimination learning in both hemispheres. The training method used permitted simultaneous presentation of discriminanda to both hemispheres of the split-brain animal. The separated hemispheres were subsequently tested individually for establishment of learning, and it was found that learning had occurred in both hemispheres, in most cases. Monocular training showed reinforcement of behavior can be produced in both hemispheres at every electrode site tested. It is concluded that unilateral pleasure-center stimulation may exert a bilateral central effect via direct and crossed projections from the brain stem.     

Hypothalamic deep brain stimulation for treatment of cluster headache

Extremely severe, unilateral, recurrent facial pain and headache, accompanied by autonomic symptoms and signs, can be identified as cluster headache attacks (CH). Despite optimal pharmacological treatment, 20% of patients will not achieve satisfactory improvement. The severity of pain is so extreme that CH has been a cause of multiple suicidal attempts among patients ineffectively treated because of CH. Hypermetabolism of ipsilateral posterior hypothalamus observed in PET studies led to multiple attempts of deep brain stimulation (DBS) utilization in CH treatment. The authors present current opinions about DBS treatment in CH. A socioeconomic analysis of neuromodulatory treatment of CH is presented.     

Hypothalamic stimulation for intractable cluster headache: long-term experience

The authors report long-term results of continuous hypothalamic stimulation in 16 chronic drug-refractory patients with cluster headache (CH). At a mean follow-up of 23 months, 13 patients are persistently pain-free or almost pain-free, and the other 3 are improved. There are no persistent side effects. Hypothalamic stimulation is an effective, safe, and well-tolerated alternative to surgery for chronic patients with drug-refractory CH.     

Postnatal stimulation of the pups counteracts prenatal stress-induced deficits in hippocampal neurogenesis.

BACKGROUND: Prenatal stress constitutes a developmental risk factor for later psychopathology. The behavioral disorders are sustained by neurobiological alterations including long-term reduction of hippocampal neurogenesis; its deregulation has been involved in cognitive impairments, mood disorders and addiction. A major goal is to define periods in development and strategies for intervening to prevent the effects of early stressful events. We investigated the ability of a postnatal infantile stimulation to prevent prenatal stress-induced alteration in hippocampal neurogenesis. METHODS: The influence of postnatal handling on prenatal stress-induced changes in hippocampal neurogenesis was examined in 4 and 26 month-old male rats. Three distinct phases of the neurogenesis were studied: proliferation, survival and neuronal differentiation. RESULTS: Prenatal stress reduced hippocampal cell proliferation all throughout life. Furthermore, the survival rate of newborn cells, the number of immature neurons and the number of differentiated new neurons were reduced in young and old prenatally-stressed rats. All those deleterious effects were counteracted by neonatal handling. CONCLUSIONS: These data show that finer aspects of brain shaping can be rewired by environmental influences occurring at sensitive phase of development. They also suggest that infantile stimulation may reverse the appearance of behavioral disorders induced by early life stress.     

Detection thresholds to stimulation of ventrobasal complex in cats

Cats were trained to indicate, by bar pressing for food rewards, their detection of stimulation of the ventrobasal (VB) complex delivered through implanted bipolar electrodes. By varying stimulus intensity it was possible to determine thresholds for detection. Scaling stimulus intensity relative to the appearance of a minimal evoked potential allowed comparisons between animals and also comparisons with results obtained by stimulation of peripheral nerve. Animals could detect VB stimulation, but only at stimulus intensities consistently stronger than those required for minimal appearance of an evoked response in ipsilateral primary somatosensory cortex. Results of VB activation differed from cutaneous nerve effects in that VB detection thresholds were markedly influenced by stimulus frequency. They were lowest at frequencies above 30 Hz and increased greatly at lower frequencies. Discomfort or pain did not seem to result even from relatively high stimulus intensities. The results compare well with observations obtained from stimulation of VB in humans. The appearance of an evoked cortical response is not necessarily correlated with behavior. Under appropriate conditions, behavior can be elicited predictably with minimal electrocortical activity; under other conditions detection may be absent even when large numbers of cortical neurons are activated. We suggest that regions of the cerebral cortex receiving thalamocortical projections from VB may not be essential in the detection process.     

Induction of spinal seizures by natural stimulation in cats

Transection of the spinal cord of the cat at a thoratic or lumbar level results, after as short a period as 12 days, in a preparation with such altered excitability that repeated natural stimulation of the dermatome just caudal to the transection site will induce, in as short a time as 3 days, seizure discharges. The trigger zone for the seizure spreads to caudal dermatomes when these caudal regions are repeatedly stimulated. The ‘typical’ T4–T7 seizure is a scratch reflex followed by the tonic-clonic seizure lasting for 20–30 s and ending with a scratch afterdischarge lasting for several minutes. Lower thoracic and upper lumbar seizures consist of tonic-clonic co-contractions of the muscles of the hindlegs, followed by rhythmical stepping movements lasting less than 1 min. Partial dorsal rhizotomy or local Cobalt application to the spinal cord may reduce the threshold for induction of seizure by natural stimulation and local Penicillin application to spinal cord induces seizure discharges similar to those induced by natural stimulation. Retransection of the spinal cord caudally, with elimination of the primary trigger zone, does not abolish the secondarily acquired triggers. The findings suggest that spinal circuits possess the ability to acquire new neuronal patterns of discharge and to transfer them to other more caudal segments.     

Neurotensin counteracts apomorphine-induced inhibition of dopamine release as studied by microdialysis in rat neostriatum

Microdialysis in the neostriatum of the halothane-anesthetized male rats was used to study the effect of neurotensin on the release of dopamine and its metabolites in the absence or presence of systemic apomorphine treatment. Perfusate levels of dopamine, 3,4-dihydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA) were assayed by high-performance liquid chromatography in combination with electrochemical detection. Perfusion with neurotensin (1000 nM but not 10 nM) increased the dialysate levels of dopamine without affecting those of DOPAC and HVA. Systemic treatment with apomorphine (0.05 and 0.5 mg/kg, s.c.) reduced the dialysate levels of dopamine, DOPAC and HVA in a dose-related way. Neurotensin (10 nM but not 1 nM) counteracted the inhibitory effect of apomorphine on dialysate levels of dopamine without affecting those of DOPAC and HVA. The results indicate a facilitatory effect of neurotensin on dopamine release in rat neostriatum. It is suggested that activation of neurotensin receptors may cause a reduction in the affinity of dopamine autoreceptors, since the low dose of neurotensin is able to counteract the inhibitory effect of apomorphine on dopamine release.