Lateral hypothalamic area and paraventricular nucleus connections with subfornical organ neurons: an electrophysiological study in the rat

The neural pathways from the lateral hypothalamic area (LHA) to the hypothalamic paraventricular nucleus (PVN) mediated by subfornical organ (SFO) neurons were examined in urethane-anesthetized male rats in order to determine the excitability of vasopressin (VP)-secreting neurons in the PVN. Microinjection of angiotensin II (AII) into the LHA excited the activity of nearly half (n = 8) of the SFO neurons (n = 18) activated antidromically by electrical stimulation of the PVN. Microinjection of AII into the LHA also caused excitation of approximately one-quarter (n = 11) of putative VP-secreting neurons (n = 45) in the PVN while the excitatory responses of the putative VP-secreting neurons were blocked or attenuated by pretreatment with the AII antagonist, saralasin (Sar), in the SFO. Electrical stimulation of the LHA, on the other hand, produced excitation (n = 17) or inhibition (n = 14) of the putative VP-secreting neurons (n = 52) in the PVN. About half of the excitatory responses to LHA stimulation were blocked or attenuated by pretreatment with Sar in the SFO, whereas the inhibitory responses were not affected. These results show some possible connections between the LHA and PVN, and suggest that AII-sensitive LHA neurons with efferent projections to the SFO may act to enhance the excitability of putative VP-secreting neurons in the PVN via an excitatory influence on the AII-sensitive SFO neurons.     

Involvement of the median preoptic nucleus in the regulation of paraventricular vasopressin neurons by the subfornical organ in the rat

Summary Extracellular recordings in urethane-anesthetized male rats indicated that electrical stimulation of the subfornical organ (SFO) alters the activity of 54 out of 62 phasically firing neurosecretory neurons in the hypothalamic paraventricular nucleus (PVN); 44 cells demonstrate an increase in excitability; 10 cells display a depression in their activity. In 14 out of 38 PVN cells tested, SFO stimulation-evoked excitations were abolished by pretreatment with the angiotensin II (ANG II) antagonist, saralasin (Sar), in the region of the median preoptic nucleus (MnPO). Inhibitory responses (n=7) were not affected. Microinjection of ANG II into the region of the SFO produced either a facilitation (n=28) or no effect (n=6) on the excitability of phasically active PVN neurosecretory cells and the facilitatory effect of 9 out of 23 cells tested was prevented by pretreatment with Sar in the region of the MnPO. All the PVN cells which had excitatory responses to either electrical (n=7) or chemical (n=9) stimulation of the SFO that were blocked following the pretreatment could also be activated by intravenous administration of ANG II. Furthermore, this activation was blocked (n=10) or attenuated (n=6) by pretreatment with Sar in the region of the MnPO. These results show an involvement of both the MnPO and the SFO for the regulation of excitability of putative vasopressin (VP)-secreting PVN neurons, and suggest that MnPO neurons sensitive to ANG II may relay activation of SFO neurons by circulating ANG II to putative VP-secreting PVN neurons which result in enhanced excitability.     

Subfornical organ and hypothalamic paraventricular nucleus connections with median preoptic nucleus neurons: an electrophysiological study in the rat

Summary The role of pathways from the subfornical organ (SFO) to the hypothalamic paraventricular nucleus (PVN) through the median preoptic nucleus (MnPO) in regulating the activity of putative vasopressin (VP)-secreting neurons in the PVN was examined in urethane-anesthetized male rats. The activity of the majority (79%) of SFO neurons antidromically identified as projecting to the MnPO was excited by microiontophoretically (MIPh) applied angiotensin II (ANG II) and the effect was blocked by MIPh-applied saralasin (Sar), an ANG II antagonist. Identified SFO neurons that were excited by MIPh-applied ANG II were also excited by intravenously administered ANG II. Electrical stimulation of the SFO produced orthodromic excitation (48%) or inhibition (24%) of the activity of MnPO neurons antidromically identified as projecting to the PVN. Identified MnPO neurons that were excited by SFO stimulation were also excited by MIPh-applied ANG II, while the remaining neurons were not affected. The excitatory responses to SFO stimulation and to MIPh-applied ANG II were both blocked by MIPh-applied Sar, whereas the inhibitory responses to SFO stimulation were not affected. ANG II injected into the region of the SFO produced either an excitation (55%) or no effect (45%) on the activity of identified MnPO neurons. Electrical stimulation of the MnPO produced orthodromic excitation (27%) or inhibition (23%) of the activity of putative VP-secreting PVN neurons. ANG II injected into the region of the MnPO produced either an excitation (31%) or no effect (69%) on the activity of putative VP-secreting PVN neurons. These observations reveal some possible interconnections between three brain regions and suggest that circulating ANG II excites a population of neurons projecting from the SFO to the MnPO, and that these neurons themselves release ANG II as an excitatory transmitter on part of MnPO neurons projecting to the PVN, thereby causing enhanced activity of putative VP-secreting PVN neurons.     

Efferent pathways from the region of the subfornical organ to hypothalamic paraventricular nucleus: an electrophysiological study in the rat

Summary Twenty-three neurons in the region of the subfornical organ (SFO) were antidromically activated by electrical stimulation of the hypothalamic paraventricular nucleus (PVN) in male rats under urethane anesthesia. Microiontophoretically (MIPh) applied angiotensin II (AII) excited the activity of all units in the region of the SFO and the effect of AII was blocked by MIPh applied saralasin (Sar), an AII antagonist, but not by atropine (Atr), a muscarinic antagonist. In these units, 12 were also excited by MIPh applied acetylcholine (ACh) while 11 were not affected and the effect of ACh was attenuated by not only MIPh applied Atr, but also Sar, suggesting that not only neurons specific for AII, but also neurons sensitive to both AII and ACh project to the PVN in the region of the SFO. Intravenously administered AII excited the activity of both types of units in the region of the SFO. Microinjected AII or ACh into the region of the SFO excited the activity of putative vasopressin (VP)-secreting units in the PVN. These results suggest that neurons projecting to the PVN in the region of the SFO may act to enhance the activity of putative VP-secreting neurons in the PVN in response to circulating AII.     

Impaired responsiveness of paraventricular neurosecretory neurons to osmotic stimulation in rats after local anesthesia of the subfornical organ

Extracellular recordings were obtained from 32 phasically active neurosecretory cells in the hypothalamic paraventricular nucleus (PVN) of urethane-anesthetized male rats. None of the PVN cells changed their activity to intracarotid infusions of isotonic saline (0.15 M NaCl solution, 0.05 ml). Of these PVN neurons, 26 displayed an increase in neuronal activity following intracarotid infusions of hypertonic saline (0.2 M NaCl solution, 0.05 ml), while the remainder were unresponsive. Microinjection of the local anesthetic lidocaine into the subfornical organ (SFO) reversibly diminished the excitatory response to the infusions of hypertonic saline in 10 out of 15 PVN neurons tested, whereas the injection of lidocaine into the vicinity of the SFO (n = 4) or the third ventricle (n = 4) did not cause a marked change. These results show an involvement of the SFO in the mechanism of osmotic activation of putative vasopressin (AVP)-secreting neurons in the PVN.     

Involvement of the septum in the regulation of paraventricular vasopressin neurons by the subfornical organ in the rat

Extracellular recordings were obtained from 58 phasically active neurosecretory neurons in the hypothalamic paraventricular nucleus (PVN) of urethane-anesthetized male rats. Of these PVN neurons, 39 exhibited an increase and 11 displayed a reduction in ongoing activity following electrical stimulation of the subfornical organ (SFO), while the remaining neurons were unresponsive. Microinjection of the local anesthetic lidocaine into the medial septum reversibly abolished the SFO stimulus-evoked reduction in 7 out of 9 PVN neurons tested, whereas similar injection was without effect on the stimulus-evoked increase in 18 out of 20 PVN neurons tested. These results suggest that the SFO efferents through the medial septum to the PVN exert a predominantly inhibitory influence on the excitability of putative vasopressin (VP)-secreting neurons in the PVN.     

Cell subpopulations of nicotine-sensitive subfornical organ neurons in rat

The subfornical organ (SFO), which is related to drinking and cardiovascular regulation, is activated by central application of nicotine (NIC) and angiotensin II (ANG). However, NIC-induced drinking is much smaller than ANG-induced one although approximately 60% of SFO neurons are affected by both NIC and ANG. Therefore, some specific subpopulations of SFO neurons for NIC or ANG may be related to such different drinking responses. To clarify subpopulations of NIC-sensitive neurons, electrophysiological properties of SFO neurons with the application of NIC was investigated at whole-cell patch-clamp recordings. Based on our developed electrophysiological criteria of the recovery kinetics of tetraethylammonium-resistant transient outward K(+) currents, two sub-types (F- and S-type neurons) were distinguished. Twenty-nine dissociated SFO neurons were examined to determine whether they showed NIC-induced inward currents. Most F-type neurons (n=19/21) showed NIC sensitivity, but most S-type neurons (n=7/8) did not. Our previous study had demonstrated that half of the F-type and all of the S-type units showed ANG sensitivity. These suggests that almost all of the NIC-sensitive SFO neurons were electrophysiologically classified as the F-type, but not S-type, and this differs in part from angiotensin sensitivity. The different subpopulations for chemical sensitivities in the SFO may be related to different drinking responses.     

Angiotensin II regulates the activity of mouse suprachiasmatic nuclei neurons

Neuropeptide signaling plays key roles in coordinating cellular activity within the suprachiasmatic nuclei (SCN), site of the master circadian oscillator in mammals. The neuropeptide angiotensin II (ANGII) and its cognate receptor AT1, are both expressed by SCN cells, but unlike other SCN neurochemicals, very little is known about the cellular actions of ANGII within this circadian clock. We used multi-electrode, multiunit, extracellular electrophysiology, coupled with whole-cell voltage and current clamp techniques to investigate the actions of ANGII in mouse SCN slices. ANGII (0.001-10 microM) dose dependently stimulated and inhibited extracellularly recorded neuronal discharge in many SCN neurons ( approximately 60%). Both actions were blocked by pre-treatment with the AT1 receptor antagonist ZD7155 (0.03 microM), while suppressions but not activations were prevented by pre-treatment with the GABA A receptor antagonist bicuculline (20 microM). AT1 receptor blockade itself suppressed discharge in a subset ( approximately 30%) of SCN neurons, and this action was not blocked by bicuculline. In voltage-clamped SCN neurons (-70 mV), AT1 receptor activation dose-dependently enhanced the frequency of action potential-driven, GABA A receptor-mediated currents, but did not alter their responses to exogenously applied GABA. In current-clamped SCN neurons perfused with tetrodotoxin, ANGII induced a membrane depolarization with a concomitant decrease in input resistance. In conclusion we show that AT1 receptor activation by ANGII depolarizes SCN neurons and stimulates action potential firing, leading to increased GABA release in the mouse SCN. Additionally we provide the first evidence that endogenous AT1 receptor signaling tonically regulates the activities of some SCN neurons.     

The A1 noradrenergic region enhances the responsivity of hypothalamic paraventricular neurohypophyseal neurons to inputs from the subfornical organ in the rat

Summary The action of the A1 noradrenergic neurons of the ventrolateral medulla on the responsiveness of neurohypophyseal neurons in the rat hypothalamic paraventricular nucleus (PVN) to inputs from the subfornical organ (SFO) was examined in antidromically identified PVN neurons that respond to electrical stimulation of both the SFO and A1 region. In both putative vasopressin (VP)- and oxytocin (OXY)-secreting PVN neurons that were classified according to their spontaneous firing patterns and their responsivity to baroreceptor activation, prior stimulation of the A1 region did not affect the short latency brief duration excitatory response induced by SFO stimulation. Simultaneous stimulation of the A1 region significantly enhanced the long latency prolonged excitatory response induced by SFO stimulation and the enhancement was blocked by microiontophoretically applied phentolamine, and -adrenoceptor antagonist, but not by timolol, a -adrenoceptor antagonist. Simultaneous stimulation of the A1 region also significantly enhanced the inhibitory response induced by SFO stimulation and the enhancement was blocked by microiontophoretically applied timolol, but not by phentolamine. These results suggest that the A1 region may act to enhance the partial excitatory (via an -adrenoceptor mechanism) and inhibitory SFO inputs (via a -adrenoceptor mechanism) to the PVN neurohypophyseal neurons as a modulatory action.     

Right atrial stretch activates neurons in autonomic brain regions that project to the rostral ventrolateral medulla in the rat

Activation of the cardiac mechanoreceptors results in changes in sympathetic nerve activity and plays an important role in the responses elicited by elevated blood volume. Stimulation of the reflex influences several key autonomic regions, namely the paraventricular nucleus (PVN), the nucleus of the tractus solitarius (NTS) and the caudal ventrolateral medulla (CVLM). Neurons in these regions project directly to the rostral ventrolateral medulla (RVLM), a critical region in the generation of sympathetic vasomotor tone. The aim of the present experiments was to determine whether neurons in the PVN, NTS and CVLM that are activated by cardiac mechanoreceptor stimulation also project to the RVLM. Animals were prepared, under general anesthesia, by microinjection of a retrogradely transported tracer into the pressor region of the RVLM, and the placement of a balloon-tipped cannula at the junction of the right atrium and the superior vena cava. On the experimental day, in conscious rats, the balloon was inflated to stimulate cardiac mechanoreceptors (n = 9), or left uninflated (control, n = 8). Compared with controls, there was a significantly increased number of Fos-immunoreactive neurons (a marker of activation) in both the PVN (2.5-fold) and NTS (two-fold), but this was not seen in the CVLM. Compared with controls, a significant number of the neurons in the PVN (8%) and NTS (4.0%) that projected to the RVLM were activated. The data suggest that subgroups of RVLM-projecting neurons located in the PVN and NTS are involved in the central reflex pathway activated by cardiac mechanoreceptor stimulation.     

Identification and characterization of two functionally distinct groups of spinal cord-projecting paraventricular nucleus neurons with sympathetic-related activity

Activation of spinal cord-projecting neurons of the hypothalamic paraventricular nucleus (PVN) has been implicated in a host of sympathetic nervous system functions. Here, we report two distinct activity patterns among electrophysiologically identified PVN spinal neurons that may contribute to the varied functional responses elicited by PVN activation. Extracellular single-unit recording was performed in anesthetized rats, and PVN neurons were antidromically identified by electrical stimulation of the spinal cord (T1-3 or T10-12). Axonal conduction velocity was determined for each identified neuron and revealed two distinct groups of cells, designated Group I (n=19) and Group II (n=34). Conduction velocity was significantly (P<0.01) different between Group I (3.67+/-0.29 m/s) and Group II (0.45+/-0.01 m/s) cells and indicates that axons of Group I cells are larger and/or more heavily myelinated than those of Group II, which appear to be unmyelinated. The majority of Group I (15/19: 79%) and Group II (23/34: 68%) cells discharged spontaneously. Basal firing rates were significantly different between groups (Group I: 2.7+/-0.85 versus Group II: 1.8+/-0.64 spikes s(-1); P<0.05). Spike-triggered averaging of renal sympathetic nerve activity revealed sympathetic-related discharge among a majority of Group I (11/15:73%) and Group II (17/23: 74%) neurons. In addition, seven of 11 Group I cells showed cardiac-related discharge. Pulse-rhythmic discharge was not detectable in any Group II cells tested (n=17). Among 11 Group I cells tested for barosensitivity, discharge in eight (73%) was graded by changes in mean arterial pressure. None of the 16 Group II cells tested for arterial pressure sensitivity responded.We conclude that the PVN spinal pathway is comprised of at least two functionally distinct cell types. The response profile and activity patterns of Group I cells suggest involvement in regulating vasomotor components of sympathetic outflow. By comparison, the activity of Groups II cells suggests a possible role in non-vasomotor sympathetic control.     

Vasopressin increases GABAergic inhibition of rat hypothalamic paraventricular nucleus neurons in vitro

This investigation used an in vitro hypothalamic brain slice preparation and whole cell and perforated-patch recording to examine the response of magnocellular neurons in hypothalamic paraventricular nucleus (PVN) to bath applications of vasopressin (VP; 100-500 nM). In 22/38 cells, responses were characterized by an increase in the frequency of bicuculline-sensitive inhibitory postsynaptic potentials or currents with no detectable influence on excitatory postsynaptic events. Perforated-patch recordings confirmed that VP did not have an effect on intrinsic membrane properties of magnocellular PVN neurons (n = 17). Analysis of intrinsic membrane properties obtained with perforated-patch recording (n = 23) demonstrated that all of nine VP-sensitive neurons showed a rebound depolarization after transient membrane hyperpolarization from rest. By contrast, 12/14 nonresponding neurons displayed a delayed return to resting membrane potentials. Recordings of reversed inhibitory postsynaptic currents with chloride-loaded electrodes showed that responses to VP persisted in media containing glutamate receptor antagonists but were abolished in the presence of tetrodotoxin. In addition, responses were mimicked by vasotocin [Phe(2), Orn(8)], a selective V(1a) receptor agonist, and blocked by [beta-Mercapto-beta, beta-cyclopentamethylenepropionyl(1),O-Me-Tyr(2), Arg(8)]-VP (Manning compound), a V(1a)/OT receptor antagonist. Neither [deamino-Cys(1),Val(4),D-Arg(8)]-VP, a selective V(2) receptor agonist, nor oxytocin were effective. Collectively, the results imply that VP acts at V(1a) receptors to excite GABAergic neurons that are presynaptic to a population of magnocellular PVN neurons the identity of which features a unique rebound depolarization. Endogenous sources of VP may be VP-synthesizing neurons in suprachiasmatic nucleus, known to project toward the perinuclear regions of PVN, and/or the magnocellular neurons within PVN.     

Effects of intracerebroventricular administration of neuropeptide W30 on neurons in the hypothalamic paraventricular nucleus in the conscious rat

We demonstrated that intracerebroventricular (i.c.v.) administration of NPW30 increases the arterial blood pressure (ABP), heart rate (HR), and plasma catecholamine concentrations in conscious rats. NPW has been reported to be an important stress mediator in the central nervous system that modulates the hypothalamus-pituitary-adrenal (HPA) axis and sympathetic outflow. To examine the effects of NPW30 on the neural activity of the hypothalamic paraventricular nucleus (PVN), which is an integrative center of the autonomic and endocrine functions relevant to stress responses, we simultaneously recorded the single-unit activity in the PVN, ABP, and HR in conscious freely moving rats. Of the non-phasic (irregular) PVN neurons (n=35) examined, NPW30 (i.c.v. 3 nmol) elicited excitation in 22 neurons, inhibition in 7 neurons, and no response in 6 neurons, accompanied with increases in ABP and HR, whereas low-dose NPW30 (i.c.v. 0.3 nmol) did not affect the unit activity, ABP, or HR. Neurons that were affected by NPW30 were then further examined for their responses to perturbation in ABP and systemic administration of cholecystokinin-8 (CCK). The majority of neurons also showed responses to CCK, phenylephrine (PE), or nitroprusside (SNP). Our data suggest that central NPW30 modulates PVN neuronal activities, which might be involved in the regulation of cardiovascular function and energy balance through the autonomic nervous system, particularly, under stress-related conditions.     

Responses of hypothalamic paraventricular neurons in vitro to norepinephrine and other feeding-relevant agents

To investigate paraventricular hypothalamic neuronal actions responsible for the effects of neurotransmitters on feeding, and to test the notion that a single population of cells there could account for feeding effects, hypothalamic slices containing the paraventricular nucleus (PVN) were prepared from rats. Electrophysiological responses of individual PVN neurons to feeding-inducing agents norepinephrine (NE) and gamma-aminobutyric acid (GABA), and to anorexic agents serotonin (5-HT) and histamine (Hist) were examined. NE inhibited neuronal activity through alpha 2-adrenergic receptors, and excited through alpha 1-receptors. alpha 2-receptors are known to mediate the behavioral effect of NE. NE inhibited most clearly those neurons that otherwise fired continuously in this type of in vitro preparation. GABA affected the activity of 37% of the neurons tested, primarily by inhibition. The inhibitory action of GABA can be related to its feeding-inducing effect. GABA in PVN can also attenuate excitatory responses and enhance inhibitory responses to NE or 5-HT. 5-HT caused excitatory and inhibitory responses with the former action outnumbering the latter by approximately 3 to 1. Since this would result in a net excitation, it appears that 5-HT in PVN inhibits feeding mainly by exciting neuronal activity. Hist excited 72% and inhibited only 2% of PVN neurons. The excitation was blocked by H1-antagonists, which have been shown to mediate Hist effect on feeding. Comparing across neurons, the inhibitory response to NE was correlated with that to GABA, but not with any responses to 5-HT or Hist. The excitatory responses to Hist correlated with 5-HT responses.(ABSTRACT TRUNCATED AT 250 WORDS)     

Paraventricular neurosecretory neurons: synaptic inputs from the ventrolateral medulla in rats

Effects of electrical stimulation of the ventrolateral medulla on discharge activity of neurosecretory neurons in the paraventricular nucleus (PVN) were studied in male rats anesthetized with urethane-chloralose. Among 35 phasically firing neurosecretory neurons, stimulation of the lateral reticular nucleus and its vicinity produced excitation in 10 and inhibition in 2. The stimulation also enhanced the activity of 40% of the PVN neurosecretory neurons that fired continuously (n = 81); of these responsive neurons, half of the neurons tested (n = 12) were inhibited by i.v. administration of phenylephrine. The result suggests that both vasopressin- and oxytocin-secreting neurons in the PVN receive mainly excitatory synaptic inputs from the ventrolateral medulla.     

Responses of neurons in paraventricular nucleus to activation of cardiac afferents and acute myocardial ischaemia in rats

Stimulation of cardiac sympathetic afferents increases sympathetic outflow and blood pressure. Chemicals released during myocardial ischaemia activate cardiac afferents. This study was to determine the responses of neurons in paraventricular nucleus (PVN) to the cardiac afferent activation caused by exogenous chemicals or myocardial ischaemia using an extracellular single-unit recording method. Rats were anaesthetized and underwent bilateral cervical vagal denervation (VD) and carotid and aortic baroreceptor denervation (BD). In 196 spontaneously active neurons in parvicellular PVN, 60 (30.6%), 36 (18.4%) and 91 (46.4%) neurons were respectively sensitive, mildly sensitive and insensitive to capsaicin, while nine (4.6%) neurons showed inhibitory responses to capsaicin. Epicardial application of capsaicin activated capsaicin-sensitive neurons in the PVN and increased mean arterial pressure. These neurons were also sensitive to exogenous bradykinin, adenosine and H(2)O(2). The neuron response is not secondary to a capsaicin-induced increase in mean arterial pressure because a similar degree of pressor response induced by aortic coarctation did not increase the neuron activity. Compared with intact rats, VD or BD or combined VD and BD increased the response of capsaicin-sensitive neurons to epicardial application of capsaicin, while stimulation of vagal afferents inhibited the response. Myocardial ischaemia caused increases in the activity of capsaicin-sensitive neurons and renal sympathetic nerve activity. The results indicate that chemical stimulation of cardiac sympathetic afferents activates capsaicin-sensitive neurons in parvicellular PVN, which is inhibited by the afferent activities of vagi and arterial baroreceptors. Acute myocardial ischaemia activates capsaicin-sensitive neurons in PVN and enhances sympathetic outflow.     

Region-specific projections from the subfornical organ to the paraventricular hypothalamic nucleus in the rat

Neurons in the subfornical organ (SFO) project to the paraventricular hypothalamic nucleus (PVN) and there, in response to osmolar and blood pressure changes, regulate vasopressin neurons in the magnocellular part (mPVN) or neurons in the parvocellular part (pPVN) projecting to the cardiovascular center. The SFO is functionally classified in two parts, the dorsolateral peripheral (pSFO) and ventromedial core parts (cSFO). We investigated the possibility that neurons in each part of the SFO project region-specifically to each part of the PVN, using anterograde and retrograde tracing methods. Following injection of an anterograde tracer, biotinylated dextran amine (BDX) in the SFO, the respective numbers of BDX-uptake neurons in the pSFO and cSFO were counted and the ratio of the former to the latter was obtained. In addition, the respective areas occupied by BDX-labeled axons per unit area of the mPVN and pPVN were measured and the ratio of the former to the latter was obtained. Similarly, following injection of the retrograde tracer in the PVN, the respective areas occupied by tracer per unit area of the mPVN and pPVN were measured and the ratio of the former to the latter was obtained. The respective numbers of retrogradely labeled neurons in the pSFO and cSFO were also counted and the ratio of the former to the latter was obtained. It became clear by statistical analyses that there are strong positive correlations between the ratio of BDX-uptake neuron number in the SFO and the ratio of BDX-axon area in the PVN in anterograde experiment (correlation coefficient: 0.787) and between the ratio of retrograde neuron number in the SFO and the ratio of tracer area in the PVN in retrograde experiment (correlation coefficient: 0.929). The result suggests that the SFO projects region-specifically to the PVN, the pSFO to the mPVN and the cSFO to the pPVN.     

Noradrenaline excites and inhibits GABAergic transmission in parvocellular neurons of rat hypothalamic paraventricular nucleus

Noradrenaline (NA) is a major neurotransmitter that regulates many neuroendocrine and sympathetic autonomic functions of the hypothalamic paraventricular nucleus (PVN). Previously NA has been shown to increase the frequency of excitatory synaptic activity of parvocellular neurons within the PVN, but little is known about its effects on inhibitory synaptic activity. In this work, we studied the effects of NA (1-100 microM) on the spontaneous inhibitory synaptic currents (sIPSC) of type II PVN neurons in brain slices of the rat using the whole cell patch-clamp technique. Spontaneous IPSCs were observed from most type II neurons (n = 121) identified by their anatomical location within the PVN and their electrophysiological properties. Bath application of NA (100 microM) increased sIPSC frequency by 256% in 59% of the neurons. This effect was blocked by prazosin (2-20 microM), the alpha(1)-adrenoceptor antagonist and mimicked by phenylephrine (10-100 microM), the alpha(1)-adrenoceptor agonist. However, in 33% of the neurons, NA decreased sIPSC frequency by 54%, and this effect was blocked by yohimbine (2-20 microM), the alpha(2)-adrenoceptor antagonist and mimicked by clonidine (50 microM), the alpha(2)-adrenoceptor agonist. The Na(+) channel blocker, tetrodotoxin (0.1 microM) blocked the alpha(1)-adrenoceptor-mediated effect, but not the alpha(2)-adreonoceptor-mediated one. Both of the stimulatory and inhibitory effects of NA on sIPSC frequency were observed in individual neurons when tested with NA alone, or both phenylephrine and clonidine. Furthermore, in most neurons that showed the stimulatory effects, the inhibitory effects of NA were unmasked after blocking the stimulatory effects by prazosin or tetrodotoxin. These data indicate that tonic GABAergic inputs to the majority of type II PVN neurons are under a dual noradrenergic modulation, the increase in sIPSC frequency via somatic or dendritic alpha(1)-adrenoceptors and the decrease in sIPSC frequency via axonal terminal alpha(2)-adrenoceptors on the presynaptic GABAergic neurons.     

Oxytocin,but not vassopressin,modulates nociceptive responses in dorsal horn neurons

Oxytocin (OT) and vasopressin (VP) are synthesized and secreted by the paraventricular hypothalamic nucleus (PVN), and both peptides have been implicated in the pain modulatory system. In the spinal cord, activation of OT-containing axons modulates nociceptive neuronal responses in dorsal horn neurons; however, it is not known whether the direct VPergic descending projection participates. Here, we show that both PVN electrical stimulation and topical application of OT in the vicinity of identified and recorded dorsal horn WDR selectively inhibit Aδ and C-fiber responses. In contrast, the topical administration of VP on the same neurons did not affect the nociceptive responses. In addition, the reduction in nociceptive responses caused by PVN stimulation or OT administration was blocked with a selective OT antagonist. The results suggest that the VP descending projection does not modulate the antinociceptive effects mediated by the PVN on dorsal horn neurons; instead, it is the hypothalamic-spinal OT projection that regulates nociceptive information.