Biomedical subjects

A V Ferguson

Publications and source records attributed to A V Ferguson.

At least 37 records · Page 2Linked to original sources

PubMed1998

Hyperpolarizing after-potentials regulate generation of long-duration plateau depolarizations in rat paraventricular nucleus neurons.

Activation of N-methyl-D-aspartate (NMDA) receptors in a population of neurons of the paraventricular nucleus (PVN) results in long-duration plateau depolarizations during which the membrane rapidly depolarizes, reaching a stable plateau near -20 mV. These responses were observed in 29% of the Type II PVN neurons tested with 1 microM NMDA agonist (n = 84). The stable plateau phase is characterized by an increase in ionic conductance, from 1.19+/-0.11 nS to 5.24+/-2.17 nS (n = 5). Bath application of tetrodotoxin (n = 4) or alternatively inclusion of QX-314 in the pipette solution (n = 3) prevented the generation of these events. The remaining cells tested (n = 56) also depolarized in response to NMDA agonist, but long duration plateau depolarizations were not observed. Previous evidence from hypothalamic cultures has demonstrated synaptically driven plateau potentials following the blockade of repolarizing conductances. Pharmacological blockade of the post-spike hyperpolarizing afterpotential with 4-aminopyridine (200 microM), in cells that did not generate plateaux, resulted in the observance of long duration plateau depolarizations in response to a subsequent application of NMDA agonist (n = 4). Our results demonstrate that this 4-aminopyridine-sensitive ionic conductance plays a critical role in determining whether a cell will depolarize for a prolonged duration in response to NMDA receptor activation. As a prolonged depolarization of the postsynaptic membrane and accompanying membrane permeability changes are essential for neurotoxicity, these findings provide evidence for a potential protective mechanism that depends solely on the ability of the cell, through its ionic conductances, to control imposed changes in membrane potential.

Animals↗

PubMed1998

Leptin depolarizes rat hypothalamic paraventricular nucleus neurons.

Leptin, the protein product of the ob/ob gene, is thought to have a central site of action, presumably within the hypothalamus, through which it regulates feeding behavior. THe paraventricular nucleus (PVN) is one structure that has been implicated in regulating feeding behavior. Using patch-clamp recording techniques, this study examines the direct membrane effects of leptin on neurons in a coronal PVN slice. Bath application of the physiologically active leptin fragment (amino acids 22-56) elicited dose-related depolarizations in 82% of the type I cells tested (n = 17) and 67% of the type II cells tested (n = 9). By contrast, the physiologically inactive leptin fragment (amino acids 57-92) had no discernible effect on membrane potential (n = 7). The effects of this peptide were unaffected following synaptic isolation of the cells by bath application of the sodium channel blocker tetrodotoxin (n = 5). Voltage clamp recordings in six cells demonstrated that leptin increased a nonspecific cation conductance with a reversal potential near -30 mV. These findings suggest that neurons in PVN may play an important role in the central neuronal circuitry involved in the physiological response to leptin.

Animals↗

PubMed1998

Leptin acts in the rat hypothalamic paraventricular nucleus to induce gastric mucosal damage.

Leptin is produced and secreted by adipocytes to regulate body weight homeostasis. Leptin acts centrally to reduce weight by decreasing food intake and increasing energy expenditure. The paraventricular nucleus (PVN) is a central nervous system structure suggested as a site at which leptin acts to exert its central effects. Leptin microinjection (10(-6) M, 0.5 microl) into the PVN of urethan-anesthetized male Sprague-Dawley rats (150-300 g) resulted in significant gastric damage (mean score = 1.75, n = 16). Damage scores were significantly different than those observed after saline microinjection into the PVN (mean score = 0.00, n = 5, P < 0. 05), or leptin microinjection into non-PVN sites (mean score = 0.33, n = 6, P < 0.05). There were no changes in blood pressure (mean area under curve = 401.9 +/- 224.2 mmHg * s, n = 11, P > 0.05) or heart rate (mean area under curve = 40.9 +/- 25.9 beats, n = 10, P > 0.05) in response to leptin microinjection into PVN. These results suggest that leptin acts on a functionally specific population of PVN neurons involved in the control of gastrointestinal function.

Animals↗

PubMed1997

Long duration pressor responses following activation of subfornical organ neurons in rats are the result of increased circulating vasopressin.

Electrical stimulation in the subfornical organ (SFO) of male Sprague-Dawley rats resulted in biphasic increases in blood pressure (BP) without a change in heart rate. The initial short duration (0-10 s) increase in BP lasted throughout the 10 s stimulation period (area under the curve (AUC) = 104.3+/-15.26 mmHg/s, (mean+/-SEM) P < 0.001). Upon termination of the electrical stimulus, the BP remained elevated for approximately 55 s (long duration response, AUC = 327.5+/-48.22 mmHg/s, P < 0.001). This long duration BP response was determined to be the result of an increase in circulating vasopressin (VP) as administration of a V1 receptor antagonist abolished this response (AUC = -210.7 +/- 42.38 mmHg/s, P < 0.01). The results of the present study demonstrate that the long duration component of the biphasic increase in BP observed on response to electrical stimulation of the SFO is the result of increased concentrations of circulating VP.

Animals↗

PubMed1997

Reduced NMDA receptor sensitivity may underlie the resistance of subpopulations of PVN neurons to excitotoxicity.

Magnocellular neurons in the paraventricular nucleus are resistant to excitotoxic cell damage. We tested the hypothesis that a modified post-synaptic response following NMDA receptor activation may underlie this resistance. Whole-cell recordings from hypothalamic slices showed that NMDA receptor activation caused dose-dependent depolarizations in both Type I (putative magnocellular) and Type II (putative parvocellular) neurons. Type II cells, however, were an order of magnitude more sensitive (10 nM) than Type I neurons (100 nM). The depolarizations recorded in Type II cells were also significantly greater (> 35% resulting in sodium channel inactivation) than those recorded in Type I neurons. This differential sensitivity of neurons to NMDA receptor activation may explain the selective resistance of magnocellular PVN neurons to excitatory neurotoxins.

2-Amino-5-phosphonovalerate↗

PubMed1997

Nitric oxide regulates NMDA-driven GABAergic inputs to type I neurones of the rat paraventricular nucleus.

1. Whole-cell recordings were obtained from type I paraventricular nucleus (PVN) neurones in coronal slices of rat hypothalamus to study the involvement of nitric oxide (NO) in the modulation of inhibitory transmission resulting from the activation of N-methyl-D-aspartate (NMDA) receptors by the high affinity receptor agonist D,L-tetrazol-5-ylglycine. 2. A brief pulse of NMDA agonist (0.1-10 microM) faithfully elicited increases in action potential firing frequency in all type I cells tested (n = 55). In cells with membrane potentials positive to -75 mV, this excitation was accompanied by an underlying depolarization (> 2 mV) in the majority of cases (n = 45). At membrane potentials negative to -75 mV, NMDA agonist application elicited an initial monotonie depolarization, which was auxiliary to profound, rhythmic oscillations of the membrane potential, resulting in the emergence of burst-like activity in these cells (n = 8). 3. In addition to depolarizing the neurones, the NMDA agonist also elicited inhibitory postsynaptic potentials (IPSPs) in 40% (n = 22) of the cells tested. The IPSPs were inhibited by the GABAA receptor antagonist bicuculline methiodide (BMI). 4. Microdialysis of NO into the PVN has been shown to increase local levels of inhibitory neurotransmitters, including GABA. The possibility that NO-induced increases in GABA lead to an increase in inhibitory synaptic activity in PVN was investigated by administering NO by three different methods. Bath application of the donor compound, S-nitroso-N-acetyl-penicillamine (SNAP; n = 7), bubbled NO solution (n = 5), or the NO precursor L-arginine (n = 6) all elicited increases in IPSP frequency. 5. Production of NO in other brain centres has been linked to the activation of the NMDA receptor. In order to determine whether the increase in IPSPs following NMDA was the result of activation of NO, the production of NO was blocked with the NO synthase inhibitor N omega-nitro-L-arginine methylester (L-NAME). Subsequent NMDA receptor activation elicited more pronounced depolarizations, but there was no accompanying increase in IPSP frequency (n = 5). 6. This study demonstrates that GABAergic inhibition resulting from NMDA receptor activation can be regulated profoundly by NO. By increasing inhibitory transmission within a nucleus, NO may serve as an important intermediary in the regulation of neuronal excitability in the central nervous system.

Animals↗

PubMed1997

Nitric oxide depolarizes type II paraventricular nucleus neurons in vitro.

Nitric oxide is a labile gas which has been implicated in neuronal signalling. The enzyme responsible for the production of this molecule is present in the paraventricular nucleus of the hypothalamus, yet a specific role for nitric oxide in neurotransmission within this nucleus remains unclear. Using whole-cell patch-clamp recordings from paraventricular nucleus neurons in a coronal hypothalamic slice, we have assessed the acute effects of nitric oxide on membrane potential and ionic conductance. Recordings were obtained from 78 neurons with a mean resting membrane potential of -57.8 +/- 0.6 mV and a mean input resistance of 972 +/- 146 M omega. Cells were electrophysiologically classified into Type I or Type II according to previously established criteria. Bath application of nitric oxide (delivered either as a gas dissolved in solution, or liberated from the donor compound, N-acetyl-S-nitroso-D-penicillamine) elicited reversible membrane depolarizations (3 mV) in 14 of the 19 Type II cells tested. These cells also exhibited a decrease in input resistance following nitric oxide application. Similar effects were observed in response to bath application of L-arginine, with 11 of 14 cells displaying depolarizations and accompanying decreases in input resistance. Inhibition of nitric oxide synthase abolished the responses to L-arginine (n=2). The nitric oxide effects persisted when voltage-activated Na+ channels were blocked by tetrodotoxin (n=6). The depolarizations observed in Type II cells were mimicked by bath application of a membrane permeable cyclic GMP analogue (8-bromo-cyclic GMP) (n=8). Furthermore, nitric oxide depolarizations were abolished by pre-treatment of the slice with the guanylate cyclase inhibitor, LY83583 (n=4). Type I cells did not depolarize in response to nitric oxide (n=11). It is concluded that nitric oxide specifically depolarizes parvocellular neurons within the paraventricular nucleus via a mechanism that requires activation of guanylate cyclase and subsequent production of cyclic GMP. These findings provide the first insight into the cellular mechanisms underlying the acute effects of nitric oxide on neurons in the paraventricular nucleus.

Animals↗

PubMed1997

Actions of angiotensin in the subfornical organ and area postrema: implications for long term control of autonomic output.

1. Considerable physiological and anatomical evidence indicates that circulating angiotensin II (AngII), plays important roles in the long-term regulation of autonomic output as a result of actions in two circumventricular structures, the subfornical organ (SFO) and area postrema (AP). 2. Extracellular recordings have demonstrated excitatory actions of AngII on neurons from both of these structures which are AT1 receptor mediated, maintained when cells are placed in synaptic isolation, and are dose dependent. Interestingly SFO neurons appear to be an order of magnitude more sensitive to AngII than those in AP. 3. Recent calcium imaging studies have demonstrated that AngII induces increases in intracellular calcium in both SFO and AP neurons. Whole cell patch recordings have also begun to provide important information suggesting that AngII actions may modulate voltage activated ion channels in these two structures to elicit its observed actions on circumventricular organs (CVO) neurons at the blood-brain interface. 4. Through these actions circulating AngII is thus able to influence efferent projections from these CVO which in turn influence the output of hypothalamic cells projecting to the posterior pituitary (vasopressin secretion), nucleus tractus solitarius (NTS), and intermediolateral cell column of the spinal cord (to influence sympathetic preganglionics), and medullary neurons in the NTS.

Angiotensin II↗

PubMed1997

Cholecystokinin activates area postrema neurons in rat brain slices.

Peripheral cholecystokinin (CCK) reduces food intake and triggers the secretion of both oxytocin and corticotropin-releasing hormone. These responses are partially initiated by activation of receptors in the peripheral endings of the vagus nerve. However, in vivo studies showing that after vagotomy systemic CCK induces fos activation of neurons in the area postrema (AP) suggest that circulating CCK may directly influence the activity of neurons in this structure. The present study was therefore designed to investigate the responsiveness of AP neurons to CCK using in vitro extracellular single-unit recording techniques. Bath application of 100 nM CCK for 200 s resulted in excitatory responses in 41% and inhibitory effects in 6% of 143 AP neurons tested. Application of multiple doses of CCK (1-100 nM) to single neurons demonstrated that CCK effects were dose dependent. The firing rate of tested neurons increased by 48 +/- 15% in response to 1 nM, by 89 +/- 22% in response to 10 nM, and by 242 +/- 77% in response to 100 nM CCK. After we blockaded synaptic transmission with a low-Ca2+/high-Mg2+ artificial cerebrospinal fluid, the excitatory effects of CCK remained in all nine neurons tested. The CCK-receptor antagonist L-364,718 had no significant effect on the responses to CCK (P > 0.1, n = 4), whereas, after perfusion of slices with the CCKB-receptor antagonist L-365,260, mean responses to CCK were significantly reduced to 12.6 +/- 4.7% of the control value (P < 0.001, n = 4). These results demonstrate a direct and dose-dependent excitatory action of CCK on AP neurons that is abolished by CCKB-receptor antagonists. These data emphasize the potential role of AP in processing afferent information derived from circulating peptide concentrations that could be involved in the regulation of food intake.

Action Potentials↗

PubMed1997

Adrenomedullin microinjection into the area postrema increases blood pressure.

Adrenomedullin (ADM) circulates in the blood at concentrations comparable to other vasoactive peptides with established roles in cardiovascular regulation. Intravenously administered ADM produces a clear hypotensive effect, whereas intracerebroventricular microinjections result in increases in blood pressure (BP). Recently, we demonstrated that ADM influences neurons of the area postrema (AP), a central nervous system site implicated in cardiovascular control. However, to address directly the physiological significance of the actions of ADM at the AP, an in vivo microinjection study was undertaken. ADM, at two concentrations (1 and 10 microM), in volumes of 50, 100, and 200 nl, was microinjected into the AP or NTS of 21 urethan-anesthetized male Sprague-Dawley rats. Microinjection of 10 microM ADM (100 nl) resulted in significant transient (2-5 min) increases in BP [120 s area under the curve (AUC): 684.3 +/- 268.6 mmHg/s (P < 0.05)], and heart rate (HR) [AUC: 12.5 +/- 4.5 beats/min (P < 0.05)]. The lower concentration of ADM (1 microM) had no effect on either BP (179.1 +/- 143.6 mmHg/s) or HR (0.8 +/- 2.6 beats/min). ADM was also microinjected into the immediately adjacent nucleus of the solitary tract, where it was found to be without effect on either BP or HR. This study demonstrates, for the first time, a physiological role for ADM acting at a specific brain site, the AP, to produce significant cardiovascular responses.

Adrenomedullin↗

PubMed1997

Vasopressin acts in the subfornical organ to decrease blood pressure.

In addition to its traditional role as a circulating vasoactive peptide, vasopressin (VP) has been shown to play significant roles in central cardiovascular processing. The recent description of VP receptors within the subfornical organ (SFO) has suggested this circumventricular organ (CVO) as a potential locus for feedback actions of circulating VP on the brain. The well-established anatomical connections between SFO and hypothalamic autonomic control centers provide further arguments in support of such a view. This study was undertaken to determine the physiological consequences of activation of VP receptors within the SFO of urethane anesthetized rats. Microinjection (0.5 microliter) of 5 pmol VP into SFO resulted in significant decreases in blood pressure (BP, mean AUC -638.3 +/- 110.3 mm Hg.s, p < 0.01, n = 13) without a change in heart rate (HR, mean AUC 7.9 +/- 14.0 beats, p > 0.05, n = 12), effects which were repeatable. These depressor effects were specific to microinjection locations within this CVO as similar VP microinjections into non-SFO tissue were without effect on BP (mean AUC 245.4 +/- 111.5 mm Hg.s, p > 0.05, n = 10), or HR (mean AUC 1.8 +/- 3.1 beats, p > 0.05, n = 9). In contrast to the former depressor effects, VP microinjection (5 pmol in 0.5 microliter) into the third ventricle produced large increases in BP (mean AUC 1,461.8 +/- 368.97 mm Hg.s, p < 0.05, n = 6) again with no change in HR (mean AUC 1.4 +/- 5.96 beats, p > 0.05, n = 6). The hypotensive effects observed in response to VP microinjection into SFO were abolished by systemic treatment with a V1 receptor antagonist (mean AUC 89.5 +/- 67.7 mm Hg.s, p > 0.05) compared to BP response before V1 receptor blockade (mean AUC -605.9 +/- 119.8 mm Hg.s, n = 4). These results suggest that the SFO may be an essential structure in the feedback control loop through which circulating VP influences descending autonomic pathways involved in cardiovascular control.

Animals↗

PubMed1997

Dissociated adult rat subfornical organ neurons maintain membrane properties and angiotensin responsiveness for up to 6 days.

We have utilised standard dissociation techniques to obtain a preparation of subfornical organ (SFO) cells that have been maintained in tissue culture for up to 1 week. Stable (> 15 min) whole cell recordings were obtained from 80 cells displaying rapid (<2 ms) voltage-dependent sodium currents (blocked by tetrodotoxin in 10 of 10 cells tested), and current evoked action potentials, which were thus classified as SFO neurons. These neurons had a resting membrane potential of-63.8 +/- 1.3 mV (mean +/- SEM), spike amplitude of 86.8 +/- 2.5 mV, and input resistance of 1.2 +/- 0.1 G omega, characteristics which did not change significantly in recordings obtained for up to 6 days after dissociation. Current clamp recording showed that of 65 cells tested with bath application of angiotensin (ANG; 1,000-10nM), 41 responded to this peptide with decreases in input resistance (control 1.4 +/- 0.16 G omega, after ANG 0.78 +/- 0.1 G omega, p < 0.0001), and depolarisations (mean 18.3 +/- 2.0 mV, p < 0.0001). Similar recordings were obtained from viable cells up to 6 days after initial cell dissociation. These studies provide the first description of the basic membrane properties of dissociated SFO neurons. The responsiveness of these cells to ANG supports the conclusion that their properties are similar to those in vivo. These data suggest that use of this technique will permit systematic analysis of the membrane events underlying the actions of multiple ligands on this uniquely specialised group of CNS neurons.

Angiotensin II↗

PubMed1996

Whole cell patch recordings from forebrain slices demonstrate angiotensin II inhibits potassium currents in subfornical organ neurons.

Whole cell patch clamp recordings have been obtained from SFO neurons in a forebrain slice preparation. Basic electrophysiological characteristics recorded from these cells in current clamp mode showed a mean resting membrane potential of -57.0 +/- 2.5 mV (+/- SEM, n = 7), mean input resistance of 900 +/- 110 M omega (n = 7), and a mean spike amplitude of 68.6 +/- 4.1 mV (n = 7), accompanied by either irregular or no spontaneous activity. All cells also demonstrated a delayed return to baseline membrane potential following large hyperpolarizing current pulses indicative of the presence of a rapidly activated transient potassium current in these neurons. Voltage clamp recordings identified both rapid transient, and a sustained outward currents which demonstrated the characteristics of IA and IK respectively. While bath administration of angiotensin II (Ang) (10(-7) M) was without effect on IK in 4 of 4 neurons tested, IA was reduced by between 20 and 100% in the same 4 neurons. These data provide the first description of the basic electrophysiological characteristics of SFO neurons recorded in forebrain slice preparations. They also provide the first direct evidence suggesting that Ang may exert its control over the excitability of SFO neurons through modulation of IA in these cells.

Angiotensin II↗

PubMed1996

Angiotensin II and glutamate influence area postrema neurons in rat brain slices.

The area postrema (AP) has been repeatedly implicated in cardiovascular regulation. Microinjection and single unit recording studies in vivo have suggested specific actions for angiotensin II (ANG) and glutamate (GLU) in controlling the excitability of AP neurons. The present study was therefore designed to examine the responsiveness of AP neurons to bath administration of these substances. Of the 133 AP neurons tested with ANG (10(-8)-10(-6) M) 40% were excited, 13% inhibited and the remainder unresponsive. The excitatory effects of ANG on AP neurons were dose-dependent. Following blockade of synaptic transmission with a low calcium high magnesium solution excitatory responses were maintained in 12 of 15 cells tested. Pretreatment of slices with the AT1 receptor antagonist losartan blocked the excitatory effects of ANG in all cells (5/5) tested. The effects of GLU on AP neurons were also examined. Of the 71 AP cells tested, 40% were excited, 10% inhibited, 8% showed excitatory responses followed by periods of inhibition while the remaining cells were unaffected. Excitatory effects of GLU were maintained in all AP neurons (7/7) tested during perfusion with low calcium, high magnesium solutions. Similar responses to NMDA were observed in four of four cells tested, suggesting these GLU actions are mediated through NMDA receptors. These data demonstrate direct excitatory actions of ANG and GLU on AP neurons which are likely mediated through the AT1 and NMDA receptors, respectively.

Angiotensin II↗

PubMed1996

Electrophysiology of the circumventricular organs.

Since the first anatomical description of the circumventricular organs (CVOs) as a structurally distinct group of regions in the central nervous system (CNS), considerable information has implicated these structures as physiologically significant autonomic control centers located at the blood-brain interface. Specialized features of these structures, such as their extensive vasculature, lack of the normal blood-brain barrier (BBB) (i.e., capillaries have a fenestrated endothelium), and dense aggregations of a variety of peptidergic receptors, support an involvement of the CVOs in communication between the circulation and the CNS. The two best understood examples of CVOs with the ability to sense circulating substances impermeable to the BBB are the subfornical organ (SFO) and the area postrema (AP). Specifically, the ability of numerous peptides to influence CNS function, as the result of actions on the neural substrate of these structures has been especially well documented. Considerable anatomical, biochemical, pharmacological, and physiological evidence has implicated these structures as CNS sites at which angiotensin (ANG), atrial natriuretic peptide (ANP), vasopressin (VP), and endothelin (ET) act to influence neuroendocrine and other more classical autonomic functions. In the following sections, we review neurophysiological studies which have provided new and exciting insights regarding the specific neural pathways and cellular mechanisms through which CVO neurons are able to exert their profound influences over central autonomic control.

Animals↗

PubMed1996

Electrophysiological properties of paraventricular magnocellular neurons in rat brain slices: modulation of IA by angiotensin II.

Whole-cell patch-clamp recordings obtained from magnocellular neurons of the hypothalamic paraventricular nucleus in brain slice preparations of adult Sprague-Dawley rats have been utilized to examine three outward potassium conductances and the ionic mechanisms through which angiotensin II exerts its neurotransmitter actions within this region. Lucifer Yellow fills showed that neurons from which we recorded had large ovoid cell bodies 11-17 microns wide and 22-35 microns long, as well as 1-3 minimally branched processes, anatomical features in accordance with those previously described for magnocellular neuroendocrine neurons. These neurons had an average resting membrane potential of -58.3 +/- 0.9 (mean +/- S.E.M.) mV, spike amplitude of 92.8 +/- 1.4 mV, and input resistance of 788.9 +/- 50.4 M omega. Most of these cells displayed irregular or continuous spontaneous activity with a mean frequency of 2.44 +/- 0.33 Hz. Voltage-clamp recordings revealed three outward potassium currents; (1) a delayed outward current (IK), (2) a Ca(2+)-dependent outward current (IK(Ca)) and (3) a transient outward current (IA). These currents were classified according to their voltage dependence, inactivation, Ca2+ dependence and pharmacology. The IK was activated by depolarization beyond -40 mV and its amplitude consistently increased with depolarizing steps. The membrane conductance underlying this current was 27.3 +/- 3.8 nS for depolarization to +50 mV. In medium containing 2 mM Ca2+, depolarization to above -20 mV evoked a slowly-activating IK(Ca) which showed minimal inactivation. This current was suppressed in Ca(2+)-free/Co2+ medium and its membrane conductance was also smaller (19.4 +/- 3.5 nS at +50 mV) than that of IK. The IA demonstrated both fast activation and inactivation and was evoked only if depolarizing pulse steps were preceded by conditioning hyperpolarization. The activation threshold was approximately -65 mV and IA amplitude increased in non-linear fashion as test voltage steps became more positive. The 90% maximum of IA conductance was 15.7 +/- 1.1 nS, and was observed at membrane potentials around -15 mV. The reversal potentials of these currents were in accordance with the K+ equilibrium potential. Tetra-ethylammonium reversibly inhibited both the peak and steady-state currents of the IK, while 4-aminopyridine suppressed the IA. Replacement of 2 mM Ca2+ with 2 mM Co2+ in our bath solution or addition of Co2+ into Ca(2+)-free medium reduced the magnitude of IA, revealing the existence of a Co(2+)-sensitive IA. Bath administration of 10(-7) M angiotensin was without significant effect on IK, but resulted in a statistically significant reduction in IA (-31.0 +/- 4.1%) in 12 of 14 paraventricular nucleus cells tested, effects which were not observed following pretreatment with the AT1 receptor antagonist losartan. We conclude that in paraventricular nucleus magnocellular cells, like other CNS neurons, at least three sets of potassium channels contribute to the outward current evoked by depolarization. Our data also demonstrate ionic mechanisms through which angiotensin may act at AT1 receptors to influence the excitability of hypothalamic neuroendocrine cells.

Angiotensin I↗

PubMed1996

Paraventricular nucleus efferents influence area postrema neurons.

Extracellular single-unit recordings were obtained from area postrema neurons (AP), and peristimulus histograms were used to determine the effects of paraventricular nucleus (PVN) stimulation on these cells from anesthetized Sprague-Dawley rats. Of 91 AP cells tested, 30.8% responded to PVN stimulation with a short-latency (28.2 +/- 3.3 ms, mean +/- SE), short-duration (49.3 +/- 8.0 ms) excitation, whereas 8.6% were inhibited. In animals that had stimulation sites outside of PVN (non-PVN), only 4 of the 72 AP cells tested (5.6%) were influenced by stimulation. These excitatory effects of PVN stimulation on AP neurons were unaffected by V1-receptor blockade. Of 93 nucleus of the solitary tract (NTS) cells tested, 38.9% responded to PVN stimulation with a short-latency (18.5 +/- 2.4 ms), short-duration (48.8 +/- 9.6 ms) excitation and 22.2% with short-latency (20.75 +/- 4.1 ms), long-duration (204.4 +/- 44.9 ms) inhibitions. In contrast, non-PVN stimulation sites influenced only 19% of NTS neurons tested, all of which were excited. These data demonstrate that activation of PVN neurons elicits excitatory effects on the majority of AP neurons influenced. They further emphasize the potential significance of descending hypothalamic inputs in controlling neuronal activity in this circumventricular organ.

Animals↗

PubMed1996

In vitro recordings from area postrema neurons demonstrate responsiveness to adrenomedullin.

Adrenomedullin (ADM) is a recently discovered 52-amino acid peptide that exerts potent vasodilatory effects in the periphery and influences the control of body fluid balance when injected centrally. In this study extracellular single-unit recordings were obtained from 94 AP neurons in rat brain slices. Bath application of ADM (10(-7) M) excited 47% (32 of 68) of cells tested, and these effects were found to be dose dependent from 10(-7) to 10(-9) M. Excitation was maintained during synaptic blockade in a low-Ca2+ artificial cerebrospinal fluid solution, demonstrating direct actions of ADM on these neurons. The remaining cells were either unaffected (n = 25) or inhibited (n = 11) by ADM. ADM (10(-7) M) also influenced the spontaneous activity of 9 (7 inhibited, 2 excited) of 16 neurons located in the nucleus tractus solitarii (NTS). However, these effects could be eliminated during synaptic blockade, suggesting indirect actions of the peptide on NTS neurons. These data demonstrate that a specific population of CNS neurons within the AP are directly influenced by ADM and suggest that ADM may exert its effects on the central control of fluid balance through direct actions at this circumventricular organ.

Adrenomedullin↗