Stimulation Of Hypothalamic Defence Area Research Articles

Neurons of the A5 region are required for the tachycardia evoked by electrical stimulation of the hypothalamic defence area in anaesthetized rats

In order to assess the possible interactions between the pontine A5 region and the hypothalamic defence area (HDA), we have examined the pattern of double staining for c-Fos protein immunoreactivity (c-Fos-ir) and tyrosine hydroxylase, throughout the rostrocaudal extent of the A5 region in spontaneously breathing anaesthetized male Sprague-Dawley rats during electrical stimulation of the HDA. Activation of the HDA elicited a selective increase in c-Fos-ir with an ipsilateral predominance in catecholaminergic and non-catecholaminergic A5 somata (P < 0.001 in both cases). A second group of experiments was done to examine the importance of the A5 region in modulating the cardiorespiratory response evoked from the HDA. Cardiorespiratory changes were analysed in response to electrical stimulation of the HDA before and after ipsilateral microinjection of muscimol within the A5 region. Stimulation of the HDA evoked an inspiratory facilitatory response, consisting of an increase in respiratory rate (P < 0.001) due to a decrease in expiratory time (P < 0.01). The respiratory response was accompanied by a pressor response (P < 0.001) and tachycardia (P < 0.001). After muscimol microinjection within the A5 region, pressor and heart rate responses to HDA stimulation were reduced (P < 0.01 and P < 0.001, respectively). The respiratory response persisted unchanged. Finally, to confirm functional interactions between the HDA and the A5 region, extracellular recordings of putative A5 neurones were obtained during HDA stimulation. Seventy-five A5 cells were recorded, 35 of which were affected by the HDA (47%). These results indicate that neurones of the A5 region participate in the cardiovascular response evoked from the HDA. The possible mechanisms involved in these interactions are discussed.

Parabrachial complex glutamate receptors modulate the cardiorespiratory response evoked from hypothalamic defense area

To characterize the possible role of glutamate in the interaction between Hypothalamic Defense Area (HDA) and Parabrachial complex (PBc) nuclei, cardiorespiratory changes were analyzed in response to electrical stimulation of the HDA (1 ms pulses, 30-50 μA given at 100 Hz for 5s) before and after the microinjection of the nonspecific glutamate receptor antagonist kynurenic acid (50 nl, 5 nmol), NMDA receptor antagonist MK-801 (50 nl, 50 nmol), non-NMDA receptor antagonist CNQX (50 nl, 50 nmol) or metabotropic glutamate receptor antagonist MCPG (50 nl, 5 nmol) within the PBc. HDA stimulation evoked an inspiratory facilitatory response, consisting of an increase in respiratory rate (p<0.001) due to a decrease in expiratory time (p<0.01). The respiratory response was accompanied by a pressor (p<0.001) and a tachycardic response (p<0.001). Kynurenic acid within the lateral parabrachial region (lPB) abolished the tachycardia (p<0.001) and decreased the magnitude of blood pressure response (p<0.001) to HDA stimulation. Similarly, the magnitude of the tachycardia and the pressor response was decreased after the microinjection of MK-801 (p<0.01 and p<0.001, respectively) and CNQX (p<0.05 in both cases) into the lPB. Kynurenic acid microinjection in this region produced an inhibition of the tachypnea (p<0.001) to HDA stimulation but the respiratory response persisted unchanged after MK-801 or CNQX microinjection into the lPB. Kynurenic acid within the medial parabrachial region (mPB) abolished the tachycardia (p<0.01) and decreased the magnitude of the pressor response (p<0.001) to HDA stimulation. MK-801 and CNQX microinjection in this region decreased the magnitude of the tachycardia (p<0.05, in both cases) and pressor response (p<0.05, in both cases). The respiratory response evoked by HDA stimulation was not changed after the microinjection of kynurenic acid, MK-801 or CNQX within the mPB. No changes were observed in the cardiorespiratory response evoked to HDA stimulation after MCPG microinjection within lPB and mPB. These results indicate that glutamate PBc receptors are involved in the cardiorespiratory response evoked from the HDA. The possible mechanisms involved in these interactions are discussed.

Interaction of medullary P2 and glutamate receptors mediates the vasodilation in the hindlimb of rat

In the nucleus tractus solitarii (NTS) of rats, blockade of extracellular ATP breakdown to adenosine reduces arterial blood pressure (AP) increases that follow stimulation of the hypothalamic defense area (HDA). The effects of ATP on NTS P2 receptors, during stimulation of the HDA, are still unclear. The aim of this study was to determine whether activation of P2 receptors in the NTS mediates cardiovascular responses to HDA stimulation. Further investigation was taken to establish if changes in hindlimb vascular conductance (HVC) elicited by electrical stimulation of the HDA, or activation of P2 receptors in the NTS, are relayed in the rostral ventrolateral medulla (RVLM); and if those responses depend on glutamate release by ATP acting on presynaptic terminals. In anesthetized and paralyzed rats, electrical stimulation of the HDA increased AP and HVC. Blockade of P2 or glutamate receptors in the NTS, with bilateral microinjections of suramin (10 mM) or kynurenate (50 mM) reduced only the evoked increase in HVC by 75 % or more. Similar results were obtained with the blockade combining both antagonists. Blockade of P2 and glutamate receptors in the RVLM also reduced the increases in HVC to stimulation of the HDA by up to 75 %. Bilateral microinjections of kynurenate in the RVLM abolished changes in AP and HVC to injections of the P2 receptor agonist α,β-methylene ATP (20 mM) into the NTS. The findings suggest that HDA-NTS-RVLM pathways in control of HVC are mediated by activation of P2 and glutamate receptors in the brainstem in alerting-defense reactions.

Cannabinoid Receptor Modulation of the Defense Response in the Dorsal Periqueductal Gray

The defense response is the coordinated reaction to physical and psychological stress, and has been validated as an experimental model of panic or fear. The hypothalamus and the midbrain periaqueductal gray (PAG) are key sites on the defense pathway from which sympathoexcitation, hypertension, tachycardia, increased muscle blood flow, analgesia, twitching of the vibrissae and hyperlocomotion can be evoked. Cannabinoids have been shown to be involved in anxiety‐related responses in the PAG and the present studies examined a role for cannabinoids in the mediation of the autonomic components of the defense response in the PAG. In anesthetized rats, microinjection of d,l‐homocysteic acid into the dorsal PAG could elicit a brisk sympathoexcitation, a pressor response and twitching of the whiskers. The hypothalamic defense area (HDA) was stimulated electrically at a site from which an intense sympathoexcitation and hypertension was evoked. The cannabinoid receptor (CB1R) antagonist AM251 was microinjected at the dorsal PAG site and the HDA stimulation was repeated. The renal sympathoexcitation was attenuated at 1 and 3 mins and the pressor response to HDA stimulation was attenuated at 3,5 and 10 mins post AM251. These data suggest that CB1R activation plays a role in the autonomic and cardiovascular responses of the defense response at the level of the dPAG. Supported by AHA Greater Midwest 0750010Z and NSF IOS 0751613.

Role of the parabrachial complex in the cardiorespiratory response evoked from hypothalamic defense area stimulation in the anesthetized rat

To analyze the role of parabrachial complex (PBc) in the modulation of cardiorespiratory response evoked from the hypothalamic defense area (HDA), cardiorespiratory changes were analyzed in spontaneously breathing anesthetised rats in response to electrical stimulation of the HDA (1 ms pulses, 30–50 μA, 100 Hz for 5 s) before and after the microinjection of muscimol (50 nl, 0.25 nmol, 5 s) within the PBc. HDA stimulation evoked an inspiratory facilitatory response, consisting of an increase in respiratory rate (p<0.001) due to a decrease in expiratory time (p<0.01). The respiratory response was accompanied by a pressor (p<0.001) and a tachycardic (p<0.001) response.Muscimol microinjection within the lateral parabrachial region (lPB) abolished the respiratory response to HDA stimulation (p<0.01) and decreased the pressor response (p<0.05). Muscimol within the medial parabrachial region and Kölliker-Fuse (mPB-KF) decreased the magnitude of the pressor (p<0.01) and tachycardic (p<0.05) responses to HDA stimulation. The respiratory response persisted unchanged.Finally, extracellular recording of putative neurons from these regions were obtained during HDA stimulation to confirm functional interaction between HDA and parabrachial regions. 105 pontine cells were recorded during HDA stimulation, 57 from the lPB and 48 from the mPB-KF. In mPB-KF 34/48 (71%) and in lPB 38/57 (67%) cells were influenced from HDA.The results indicate that neurons from different regions of the PBc have an important function in mediating the cardiorespiratory response evoked from the HDA. The possible mechanisms involved in these interactions are discussed.

Role of medullary glutamatergic and purinergic P2x receptors in cardiovascular adjustments during defense reactions

Previously we demonstrated that P2x receptors in the nucleus tractus solitarius (NTS) mediate muscle vasodilation induced by electrical stimulation of the hypothalamic defense area (HDA). In the present study we sought to determine the role of P2x and glutamatergic receptors located in the rostral ventrolateral medulla (RVLM) in cardiovascular responses induced by HDA stimulation.

Effect of stimulation of anterior hypothalamic area on urinary bladder function of the anesthetized rat.

The hypothalamus is a key area for the integration of the autonomic features of affective behavior. Hypothalamic defence area (HDA) stimulation evokes major cardiorespiratory changes as well as modifications of general autonomic activity both in the anesthetized and conscious animal. Micturition is due to an increase in pelvic parasympathetic activity and, in the cat, the anterior hypothalamus has been implicated in urinary bladder control with the demonstration of a dorsolateral vesicoconstrictor pathway and a ventromedial inhibitory pathway. In this study we have investigated the effect of electrical and chemical stimulation of the HDA on bladder pressure and contractions in rat. Female rats (n = 15) were anesthetized, paralyzed and ventilated artificially. Arterial blood pressure, heart rate, urinary bladder pressure and pelvic nerve activity were recorded. HDA was electrically (1 ms, 100 Hz, 5-10 s train at intensities up to 150 micro A) and chemically (sodium glutamate, 50 nl, 2mM) stimulated. For statistical analysis the t-test was used, data were expressed as mean +/- SEM. Values of t were taken as significant when p < 0.05.HDA stimulation at 100-150 micro A evoked changes of both mean blood pressure (mBP) and bladder pressure (BlP). However, stimulation at < 30 micro A allowed a distinction within HDA of two different regions, at the same antero-posterior and lateral level, but separated 100-150 micro m in depth, which evoked differential effects on blood pressure and urinary bladder pressure. Results show that low intensity stimulation at ventral sites evoked a significant increase of mBP (from 102 +/- 5.9 to 127 +/- 8.6 mmHg, n = 10, p < 0.0001) with little changes of BlP (from 12 +/- 2.2 to 16 +/- 2.9 cmH(2)O, n = 10, p < 0.0005), whilst at more dorsal sites significant increases of BlP were elicited (from 12 +/- 8.3 to 38 +/- 4.6 cmH(2)O,n = 10, p < 0.0001) with only a small rise of mBP (from 102 +/- 6.2 to 111 +/- 9.8 mmHg, n = 10, p < 0.005). Glutamate injections at dorsal sites evoked a rise of BlP (from 11 +/- 2.2 to 30 +/- 3.0 cmH(2)O (n = 5; p < 0.0001) with small changes in BP, whilst at ventral sites (n = 4) glutamate microinjections evoked changes in BP but not of BlP. In conclusion stimulation at different sites within HDA can elicit separate changes in BP and BlP.

Angiotensin AT1 receptor antagonist losartan and the defence reaction in the anaesthetised rat. Effect on the carotid chemoreflex.

Modulation at the level of the nucleus tractus solitarii (NTS) appears to be an effective way of controlling cardiovascular reflexes. Angiotensin II acting on angiotensin AT1 receptors at the central nervous system appears to have an important role in these modulatory processes. The hypothalamic defence area (HDA) is a potential source of descending fibres containing angiotensin II that innervate the NTS. We investigated the effect of AT1 receptor blockade in the NTS on the response to stimulation of HDA in anaesthetised rats treated with the neuromuscular blocking agent pancuronium bromide. The characteristic increase in heart rate, blood pressure and phrenic nerve activity evoked by electrical stimulation of HDA is decreased by the microinjection of the AT1 receptor antagonist losartan into the NTS and the cardiovascular response to carotid body chemical stimulation is also reduced. These results support the hypothesis that AT1 receptors in the NTS play a role in the modulation of cardiovascular reflexes, and modify the influence exerted on the processing of these reflexes by other areas of the central nervous system.

Rapid adenosine release in the nucleus tractus solitarii during defence response in rats: real-time measurement in vivo.

We have measured the release of adenosine and inosine from the dorsal surface of the brainstem and from within the nucleus tractus solitarii (NTS) during the defence response evoked by hypothalamic stimulation in the anaesthetised rat. At the surface of the brainstem, only release of inosine was detected on hypothalamic defence area stimulation. This inosine signal was greatly reduced by addition of the ecto-5'-nucleotidase inhibitor alpha,beta-methylene ADP (200 microM), suggesting that the inosine arose from adenosine that was produced in the extracellular space by the prior release of ATP. By placing a microelectrode biosensor into the NTS under stereotaxic control we have recorded release of adenosine within this nucleus. By contrast to the brainstem surface, a fast increase in adenosine, accompanied only by a much smaller change in inosine levels, was seen following stimulation of the hypothalamic defence area. The release of adenosine following hypothalamic stimulation was mainly confined to a narrow region of the NTS some 500 microm in length around the level of the obex. Interestingly the release of adenosine was depletable: when the defence reaction was evoked at short time intervals, much less adenosine was released on the second stimulus. Our novel techniques have given unprecedented real-time measurement and localisation of adenosine release in vivo and demonstrate that adenosine is released at the right time and in sufficient quantities to contribute to the cardiovascular components of the defence reaction.

A role for adenosine in modulating cardio-respiratory responses: a mini-review

Evidence is provided that purine nucleotides play a major role in modulating cardio-respiratory control through actions at specific sites in the central nervous system (CNS). The accumulation of adenosine in the extracellular space of the nucleus tractus solitarius (NTS) on hypothalamic defence area stimulation is described, and is shown to result from the extracellular breakdown of neurally released adenosine triphosphate (ATP). The actions of adenosine in modulating synaptic actions in the NTS are discussed in relation to the potential presynaptic action of adenosine in modulating transmitter release. Actions of adenosine and ATP at other sites in the medulla concerned with cardio-respiratory control are discussed. The inter-relationships between ATP and adenosine are mentioned.

A source of adenosine involved in cardiovascular responses to defense area stimulation.

We have investigated the source of central adenosine important in modulating the cardiovascular response to hypothalamic defense area (HDA) stimulation in alpha-chloralose-anesthetized rats. Microinjections of an ecto-5'-nucleotidase inhibitor, alpha,beta-methylene ADP (alpha,beta-meADP), were made into caudal nucleus of the solitary tract (cNTS) and rostral ventrolateral medulla (RVLM), and its effects on HDA-evoked responses were observed. Stimulation of HDA evoked an increase in arterial pressure and a secondary rise in arterial pressure after stimulation ceased. There was also an increase in heart rate and hindlimb blood flow. alpha,beta-meADP had no effect on resting levels of arterial pressure, heart rate, and hindlimb blood flow when injected into the cNTS or RVLM. alpha,beta-meADP also had no effect on the HDA-evoked tachycardia and increase in muscle blood flow. However, alpha,beta-meADP reduced the primary increase in arterial pressure evoked by HDA stimulation when microinjected into the cNTS. In contrast, alpha,beta-meADP reduced the secondary increase in arterial pressure when microinjected into the RVLM. From these results, we suggest that at least part of the adenosine released centrally during HDA stimulation is derived extracellularly from ATP metabolism.

Behavioral characteristics of defense and vigilance reactions elicited by electrical stimulation of the hypothalamus in rabbits

An automated tracking system was used to assess the behavioral changes elicited by electrical stimulation of the hypothalamic sites that yield the cardiorespiratory components of defense reaction and vigilance reaction in rabbits. Electrical stimulation of the hypothalamic defense area (HDA) at intensities near threshold led to cessation of body movements coupled with head movements suggesting increased attention to the environment. HDA stimulation at higher intensities evoked agitated running and hindlimb thumping; the amount of running was proportional to stimulus intensity. Electrical stimulation of the hypothalamic vigilance area (HVA) at intensities near threshold elicited orienting behaviors that were similar to those elicited by stimulating the HDA at low suprathreshold current intensities. Stimulation of the hypothalamic vigilance area (HVA) at higher intensities elicited phasic immobility, increased extensor muscle tension, and head tremor. The behavioral changes elicited by HDA and HVA stimulation were accompanied by pupil dilation and exophthalmos.

Modulation of the baroreceptor reflex by stimulation of the hypothalamic defense and vigilance areas

Electrical stimulation of the hypothalamic defense area (HDA) elicits a pressor/tachycardia response that is believed to prepare an animal for fight or flight. In contrast, electrical stimulation of the hypothalamic vigilance area (HVA) evokes a pressor/bradycardia response that is associated with the inhibition of movement. The differences in the behavioral components of these two affective response patterns suggest differential modulation of the baroreceptor reflex. The present study tested this idea by assessing the effects of electrical stimulation of the HDA and the HVA upon the bradycardia/depressor response elicited by stimulation of the aortic nerve (AN) in rabbits. Concurrent HDA and AN stimulation was observed to attenuate the AN-elicited bradycardia but enhanced the depressor response elicited by AN stimulation. In contrast, concurrent stimulation of the HVA and AN enhanced the bradycardia elicited by AN stimulation but reduced the magnitude of the AN-elicited depressor response. These results provide evidence for differential modulation of the baroreceptor reflex during the defense and vigilance reactions.

Role of brainstem adenosine A1 receptors in the cardiovascular response to hypothalamic defence area stimulation in the anaesthetized rat.

1. The role of centrally located adenosine A1 receptors in the cardiovascular changes associated with the hypothalamic defence response has been investigated by in vitro autoradiography and the intraventricular application of an A1 receptor antagonist. 2. 8-Cyclopentyl-1,3-dipropylxanthine (DPCPX), a highly selective adenosine A1 antagonist and its vehicle, ethanol, were administered directly into the posterior portion of the fourth ventricle of alpha-chloralose anaesthetized, paralysed and artificially ventilated rats. 3. DPCPX (0.01 to 0.3 mg kg-1) caused a dose-dependent decrease in the magnitude of the evoked pressor response (from -13 to -23 mmHg) elicited on hypothalamic defence area stimulation at a dose 10 fold lower than that required to produce an equivalent effect following systemic administration whilst ethanol, the vehicle, had no effect. 4. In vitro autoradiography revealed a heterogeneous distribution of adenosine A1 binding sites in the lower brainstem of rats. Image analysis showed the ventrolateral medulla to have the highest density of A1 receptors. Intermediate levels of binding were seen in caudal regions of the nucleus tractus solitarii and the hypoglossal nucleus. 5. These data imply that a proportion of the cardiovascular response to hypothalamic defence area stimulation are produced by the activation of adenosine A1 receptors localized close to the surface of, or adjacent to, the fourth ventricle in the immediate vicinity of the injection site.

Hypothalamic modulation of laryngeal reflexes in the anaesthetized cat: role of the nucleus tractus solitarii.

1. This investigation was initiated because activation of laryngeal afferents, either by electrical stimulation of the superior laryngeal nerve (SLN) or by natural stimulation of receptors in the laryngeal mucosa, results in a cardiorespiratory response comprising bradycardia, hypotension and apnoea (phrenic nerve activity was suppressed). This pattern of response is qualitatively equivalent to the response that is evoked on activation of the arterial baroreceptors. 2. Preliminary studies indicated that the effects of activating the SLN were suppressed during stimulation in the hypothalamic defence area (HDA) at points that also blocked the effects of baroreceptor stimulation. 3. Recordings were taken from seventy-two neurones localized within the ipsilateral nucleus tractus solitarii (NTS) whose activity was modified by SLN stimulation. Sixty neurones responded with an EPSP on SLN stimulation; nine of these had an inspiratory firing pattern. Five neurones were seen to receive an IPSP on SLN stimulation. 4. Five respiratory SLN-activated neurones were unresponsive to stimulation of the other nerve inputs, whilst four received convergent EPSP inputs on sinus nerve (SN) stimulation. One cell of these four also received inputs from the aortic and the vagus nerves. Sixty-one non-respiratory SLN-activated neurones also received convergent inputs from the sinus nerve. Of these, fifty displayed an EPSP, four an IPSP and seven an EPSP-IPSP. Fifteen neurones also received inputs from the aortic nerve and seventeen from the vagus. 5. From the population of neurones affected by SLN stimulation, twenty-four of seventy were also influenced by HDA stimulation (3 were respiratory cells). Sixteen of these responses consisted of an EPSP (2 respiratory cells), five of an IPSP (1 respiratory cell) and three of an EPSP-IPSP. 6. In neurones receiving an IPSP on HDA stimulation, the SLN-evoked excitatory response was reduced throughout the period of HDA-evoked inhibition. These neurones were all shown to receive excitatory inputs from the arterial baroreceptors and laryngeal mechanoreceptors. 7. Additionally, in the thirty-seven neurones that were excited by SLN stimulation but received no direct synaptic input on HDA stimulation, a conditioning stimulus to the HDA evoked a block of SLN-evoked responses without an accompanying change in membrane potential. Several of these neurones were also affected by both baroreceptor and laryngeal mechanoreceptor stimulation. 8. These observations are discussed in the context of the role of the NTS in cardiorespiratory control. The potential importance of these interactions in respiratory distress are highlighted and the implications for the organization of central pathways for the control of autonomic and respiratory function are discussed.

The pattern of excitatory inputs to the nucleus tractus solitarii evoked on stimulation in the hypothalamic defence area in the cat.

1. In anaesthetized, paralysed and artificially ventilated cats, recordings have been made in the nucleus tractus solitarii (NTS) to assess further the role of this nucleus in mediating the cardiorespiratory responses that are elicited on stimulation within the hypothalamic defence area (HDA). 2. The responses of NTS neurones to stimulation in the hypothalamus were assessed, as were their patterns of evoked response to electrical stimulation of the sinus (SN), aortic (AN), superior laryngeal (SLN) and vagus (VN) nerves. 3. Stimulation in the HDA affected the activity of 110 NTS neurones (85 studied in intracellular and 25 studied in extracellular recordings). The present study focused on those sixty-eight neurones that were excited by such stimulation (51 intracellular recordings and 17 extracellular recordings). 4. Of the sixty-eight neurones that were excited by HDA stimulation, seven revealed no changes in membrane potential or evoked discharge (2 neurones) but the stimulus facilitated the excitatory effects of stimulating either (or both) the SN and SLN. An additional group of neurones showed powerful excitatory responses to HDA stimulation (15 studied with extracellular and 35 with intracellular recording). Evoked EPSPs had onset latencies in the range of 1-30 ms. Of those thirty-five neurones displaying EPSPs, twenty-six were shown to receive convergent inputs on nerve stimulation. In nine neurones the early EPSP in response to HDA stimulation was followed by an IPSP. 5. In a further group of neurones HDA stimulation elicited a long-lasting IPSP, but this was not analysed further because its features have been described in detail in earlier studies from this laboratory. 6. The patterns of response of several neurones excited by stimulation in the HDA are consistent with them forming a group of NTS interneurones that mediate the hypothalamically evoked cardiovascular responses, including modulation of reflex function, which is a major feature of cardiorespiratory control. This possibility is discussed in the light of the present physiological observations and descriptions of an intrinsic NTS group of GABA-containing neurones that have been suggested to fulfil such a role.

Hypothalamic modulation of the arterial chemoreceptor reflex in the anaesthetized cat: role of the nucleus tractus solitarii.

1. There is evidence in the literature of a mutual facilitatory interaction between the arterial chemoreceptor reflex and the alerting stage of the defence reaction, particularly in relation to the patterning of cardiorespiratory activity. The present study has been designed to test the hypothesis that a portion of this interaction involves synaptic interactions within the nucleus tractus solitarii (NTS). 2. The study has involved an analysis of the effective interactions between the stimulation of the arterial chemoreceptors and the hypothalamic defence area (HDA) on the activity of NTS neurones recorded in anaesthetized, paralysed and artificially ventilated cats. 3. A group of eighteen NTS neurones was classified as chemosensitive, on the basis of displaying EPSPs on sinus nerve stimulation (SN) and their failure to show an excitatory response to baroreceptor stimulation. Thirteen of these neurones displayed pronounced excitatory responses to chemoreceptor stimulation. In sixteen of these neurones HDA stimulation elicited an EPSP; in four of these sixteen neurones this early EPSP was followed by an IPSP. In the remaining two (of 18) neurones HDA stimulation provoked no obvious synaptic response but facilitated the efficacy of both chemoreceptor inputs and SN stimulation. 4. Neurones shown to receive convergent inputs from the arterial chemoreceptors (and SN stimulation) and HDA, often displayed excitatory responses to stimulation of other peripheral inputs. Vagally evoked EPSPs were observed in nine neurones, SLN-evoked responses in seven neurones and aortic nerve-evoked EPSPs in three neurones. 5. The organization of these synaptic interactions is discussed and these data are used to explain the pattern of interaction between chemoreceptor, baroreceptor and HDA inputs within the NTS. Conclusions are drawn regarding the functional role of different classes of NTS neurone, based on the findings in this and the accompanying two papers.

A potential role of central A 1 adenosine receptors in the responses to hypothalamic stimulation in the anaesthetized cat

In pentobarbitone anaesthetized and paralysed cats the effects of the A 1 adenosine antagonist 8-cyclopentyl-1,3-dipropylxanthine (DPCPX) have been observed on the pressor response to stimulation of the hypothalamic defence area (HDA) and on the effects of baroreceptor and chemoreceptor reflex activation on arterial blood pressure. The administration of DPCPX decreased the magnitude of the HDA pressor response and the chemoreceptor induced rise in blood pressure. The fall in blood pressure induced by baroreceptor activation was enhanced to a small yet significant extent. No changes were observed in the tachypnoea evoked by hypothalamic defence area (HDA) stimulation. These results suggest a possible role for central adenosine A 1 receptors in mediating the cardiovascular changes evoked during HDA stimulation.

Basal and reactive plasma catecholamine levels under stress and anesthesia in rabbits

The present study was undertaken to determine if electrical stimulation of the hypothalamic defense area (HDA) and baroreflex activation elicited by head up body tilt produced changes in plasma catecholamine (CA) levels in anesthetized rabbits. We also compared the effects of two anesthetics, isoflurane and sodium pentobarbital, upon basal and reactive CA levels, and upon autonomic reactivity. HDA stimulation was found to produce significant increases in plasma norepinephrine (NE) levels but not epinephrine (E) levels. Passive tilt was found to produce statistically significant increases in NE levels for both anesthetics used and a significant increase in E levels for animals anesthetized with isoflurane. Basal and reactive measurements provided evidence that pentobarbital has a more suppressive effect upon the autonomic nervous system than isoflurane: (a) Basal NE levels were significantly lower in pentobarbital-anesthetized animals than in isoflurane-anesthetized animals; and (b) Baroreceptor sensitivity to a passive tilt stressor was significantly higher for animals anesthetized with isoflurane than for animals anesthetized with pentobarbital.

Modulation of neuronal firing in the medullary solitary complex by electrical stimulation of the hypothalamic defense and vigilance areas in rabbits

The present study sought to establish functional connections between two regions in the hypothalamus associated with the cardiorespiratory concomitants of affective behavior, and neurons in the dorsal medulla thought to be involved in the mediation of the baroreceptor reflex. Single cell recordings were made in the solitary complex of the medulla (nucleus of the tractus solitarius and dorsal vagus nucleus) of anesthetized rabbits. An attempt was made to modulate the activity of these neurons by electrically stimulating two hypothalamic sites: the hypothalamic defense area (HDA) and the hypothalamic vigilance area (HVA). Responses of solitary complex neurons to a bolus injection of phenylephrine and an injection of physiological saline in a blind sac preparation were assessed in order to test for baroreceptor input. Electrical stimulation of the HDA or the HVA was found to decrease the firing rate of most solitary complex neurons that responded to hypothalamic stimulation. The cells that did show an increase in firing rate were responding to HVA stimulation. Ninety-two percent of the neurons in the solitary complex that responded to HDA or HVA stimulation were also affected by baroreceptor activation. The connections between the HDA, HVA and the solitary complex may account, in part, for the distinctive patterns of cardiorespiratory responses observed when stimulating these two hypothalamic regions.