Stimulation Of Hypothalamic Defence Area Research Articles

Arterial baroreflex inhibition by midbrain periaqueductal grey in anaesthetized rats

Midbrain periaqueductal grey (PAG) provokes the defense reaction when stimulated. The present study was conducted to determine whether, and how, the PAG produces baroreflex inhibition, a feature characterizing the hypothalamic defense reaction. In chloralose-urethane anaesthetized rats, baroreflex vagal bradycardia and baroreflex hypotension were provoked by aortic depressor nerve stimulation. When the PAG was electrically stimulated baroreflex vagal bradycardia was remarkably suppressed; suppression of baroreflex hypotension was observed following bilateral vagotomy. In contrast, chemical stimulation of the PAG by D,L-homocysteic acid microinjection markedly suppressed baroreflex vagal bradycardia but only minimally suppressed baroreflex hypotension. These findings suggest that whereas overall PAG stimulation inhibits not only cardiac but also vascular components of baroreflexes, inhibition of the latter component either depends largely on activation of passing fibers or requires recruitment of a larger number of PAG cell bodies. PAG inhibition of baroreflex vagal bradycardia was not affected following spinal cord transection at C1, indicating that the inhibition was exclusively central in origin and not due to peripheral, prejunctional inhibition of vagal acetylcholine release by increased cardiac sympathetic nerve activities. The PAG inhibition of baroreflexes was greatly attenuated following electrolytic as well as chemical destruction of the parabrachial region. On the other hand, when the PAG was extensively lesioned, baroreflex inhibition produced by hypothalamic defense area stimulation was markedly diminished. PAG excitation thus causes powerful inhibition of arterial baroreflexes which is mediated by the parabrachial region; the PAG also mediates a major fraction of hypothalamic inhibition of the baroreflexes.

Electrophysiological evidence for hypothalamic defense area input to cells in the lateral tegmental field of the medulla of rabbits

Single cell recordings were made from neurons in the lateral tegmental field of the medulla (LTFM) during electrical stimulation of the hypothalamic defense area (HDA) of the rabbit. Fifty-four cells were inhibited by HDA stimulation; 23 of these cells received barosensory input. Twenty-two LTFM cells showed an increase in firing rate during HDA stimulation; 10 of these cells received barosensory input. The results of this study provide evidence that the hypothalamic defense area makes functional connections with cardiovascular-influenced neurons in the LTFM.

Baroreceptor inputs to the nucleus tractus solitarius in the cat: modulation by the hypothalamus.

1. The effects of stimulation within the hypothalamic defence area (HDA) on the activity of neurones in the nucleus of the solitary tract (NTS) have been investigated in vivo. 2. HDA stimulation exerted marked influences on NTS neurones. Approximately two-thirds of units receiving a carotid sinus nerve (SN) input were inhibited by HDA stimulation. All units shown to receive an excitatory input from carotid sinus baroreceptors were inhibited by HDA stimulation. 3. The specificity of the HDA stimulation was investigated by generalized hypothalamic stimulation. In these experiments the number of units activated by SN stimulation that were inhibited was reduced considerably. A much smaller percentage (27%) of baroreceptive units were inhibited from hypothalamic stimulation outside the defence area. 4. Intracellular recordings revealed that HDA stimulation evoked a long-lasting hyperpolarization of membrane potential that resulted from postsynaptic inhibition (rather than disfacilitation). The HDA-evoked IPSP 'shunted' the SN-evoked EPSP when the SN stimulus was timed to occur during the initial peak hyperpolarizing phase of the HDA-evoked IPSP. 5. HDA stimulation disinhibited cells receiving an inhibitory input from the carotid sinus baroreceptors. 6. The effects of HDA stimulation were not limited to cells receiving SN afferent information or to cells within the NTS. 7. Our results explain, at the intracellular level, the mechanism for the central suppression of the baroreceptor reflex that forms an integral part of the defence response in the cat.

Hypothalamic inhibition of neurones in the nucleus tractus solitarius of the cat is GABA mediated.

1. In pentobarbitone-anaesthetized cats extracellular activity of neurones in the vicinity of the nucleus tractus solitarius receiving inputs from the carotid sinus nerve (SN) and/or vagus nerve (VN) during stimulation of the hypothalamic defence area (HDA) and application of gamma-aminobutyric acid (GABA) and glycine and their antagonists have been studied. 2. A total of forty neurones have been tested, of which twenty-four only had an input from the SN, one only from the VN, twelve from both nerves and three had neither SN or VN inputs. 3. Short trains of stimuli to the HDA inhibited both the ongoing activity (if present) and evoked discharge in thirty-nine of the forty neurones tested. 4. In the forty cells tested ionophoretic application of GABA reduced (4) or totally inhibited (35) neuronal discharge whilst in the thirty-eight tested with glycine discharge was totally (25) or partially (12) suppressed. 5. Ionophoresis of bicuculline totally (14) or partially (6) antagonized the inhibitory actions of GABA in the twenty-five cells tested, and in eighteen of these the ongoing and/or evoked activity was simultaneously increased. In eighteen of the nineteen cells tested this level of bicuculline also antagonized the inhibitory actions of HDA stimuli whereas in none of the sixteen cells tested did it affect glycine-evoked inhibitions. 6. Ionophoretic application of strychnine antagonized the inhibitory effects of glycine in eight of nine cells tested but in these eight cells strychnine had no effect on ongoing or evoked discharges, GABA- or HDA-evoked inhibitions. 7. In a chloralose-anaesthetized cat five neurones receiving SN inputs (three also receiving VN inputs) were recorded. All could be inhibited by HDA stimuli and by application of GABA. In the three of four cells in which bicuculline antagonized GABA inhibitions, the effects of HDA stimuli were simultaneously antagonized whereas glycine-evoked inhibitions were unaffected. 8. In two neurones, in addition to inhibiting neuronal discharge HDA stimulation also evoked activity in the cells. In a further four neurones similar excitatory responses were uncovered when the HDA inhibitory effects were antagonized by bicuculline. 9. The importance of these observations in cardiovascular control and in the functioning of the baroreceptor reflex is discussed.

MECHANISM OF HYPOTHALAMIC CONTROL OF CARDIAC COMPONENT OF SINUS NERVE REFLEX

The modulatory influence of hypothalamic structures on sinus nerve induced bradycardia was investigated in anaesthetized cats. Stimulation of the hypothalamic defence area inhibits the bradycardia produced by sinus nerve stimulation both in intact animals and also in animals with the spinal cord sectioned at C1 or C6. This inhibition was accompanied in the normal animal by an increased sympathetic discharge and by a sustained inspiration or tachypnoea. The same respiratory effects were noted in a spontaneously breathing C6 spinal animal, while an artificially ventilated C1 spinal animal still displayed a powerful central inspiratory drive in its recurrent laryngeal electroneurogram. The presence of central inspiratory activity was found to be an absolute impediment to the development of bradycardia. If this activity was eliminated by simultaneous stimulation of the superior laryngeal nerve, it was possible to obtain bradycardia during combined sinus nerve and hypothalamic defence area stimulation, though this bradycardia was modified by the presence of sympathetic discharge. The level of sympathetic neural discharge affects the magnitude of the bradycardia produced by sinus nerve stimulation. The bradycardia was less with normal or augmented level of sympathetic activity and was greater if this activity was reduced or absent. A lesion just caudal to the mammillary bodies disclosed a tonic hypothalamic influence both on respiration and on sympathetic discharge; stimulation of the sinus nerve produced a much more powerful bradycardia after the lesion. The existence of a respiratory "gate" through which afferent stimuli pass on their way to the nucleus ambiguus, and which can be operated by the hypothalamic defence and depressor areas, is postulated and discussed.