The Experts below are selected from a list of 177 Experts worldwide ranked by ideXlab platform
Alastair V. Ferguson - One of the best experts on this subject based on the ideXlab platform.
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Leptin influences the excitability of Area Postrema neurons
American journal of physiology. Regulatory integrative and comparative physiology, 2015Co-Authors: Pauline M. Smith, Paulina Brzezinska, Fabien Hubert, Andrea Mimee, Donald H. Maurice, Alastair V. FergusonAbstract:The Area Postrema (AP) is a circumventricular organ with important roles in central autonomic regulation. This medullary structure has been shown to express the leptin receptor and has been suggest...
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ghrelin modulates electrical activity of Area Postrema neurons
American Journal of Physiology-regulatory Integrative and Comparative Physiology, 2009Co-Authors: Mark Fry, Alastair V. FergusonAbstract:Ghrelin, a peptide hormone secreted from the stomach, is known to have a potent appetite-stimulating activity. Recently, it has been shown that Area Postrema (AP), a caudal brain stem center that l...
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Modified cardiovascular sensitivity of the Area Postrema to vasopressin in spontaneously hypertensive rats.
Brain research, 1994Co-Authors: Vicki L. Lowes, Alastair V. FergusonAbstract:Vasopressin has been shown to act at the Area Postrema to increase the sensitivity of the baroreceptor reflex. We have previously demonstrated that microinjection of vasopressin into the Area Postrema of Sprague-Dawley rats elicits pressor effects. We report here that vasopressin microinjection into the Area Postrema of spontaneously hypertensive rats is without effect on blood pressure, whereas microinjection into age-matched Wistar-Kyoto controls results in significant increases in blood pressure at 50 and 100 pg. These results suggest an altered sensitivity of the Area Postrema to vasopressin in this genetic model of hypertension.
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Circulating vasopressin influences Area Postrema neurons.
Neuroscience, 1994Co-Authors: P.m. Smith, V.l. Lowes, Alastair V. FergusonAbstract:Abstract Extracellular single-unit recordings were obtained from 107 Area Postrema and 74 nucleus tractus solitarius neurons in sodium pentobarbitol anaesthetized rats. Systemic administration of vasopressin (1–10 ng) decreased the firing frequency of 45.8% of Area Postrema neurons and 58.1% of nucleus tractus solitarius neurons tested while the firing frequency of 38.3% of Area Postrema neurons and 21.6% of nucleus tractus solitarius neurons was increased by this peptide. To determine whether these neurons were specifically influcenced by vasopressin or the accompanying pressor response, the effects of α-adrenergic agonists on neuronal activity were also determined. Cells that responded similarly to vasopressin and the change in blood pressure elicited by a-adrenergic agonists were classified as “blood pressure-sensitive”, whereas those neurons that responded differently to both agents were classified as “vasopressin-sensitive” neurons. The majority (85.2%) of Area Postrema cells that decreased firing frequency in response to vasopressin were determined to be “vasopressin-sensitive”, while 68.8% of Area Postrema neurons responding to vasopressin with increases in firing frequency were classified as “blood pressure-sensitive”. In contrast, 78.6% of nucleus tractus solitarius neurons that decreased firing frequency in response to vasopressin and 55.5% of those that increased firing frequency were classified as “blood pressure-sensitive” neurons. To determine whether the actions of vasopressin in the Area Postrema were mediated by V1 receptors the effect of vasopressin after V1 receptor blockade was examined in seven “vasopressin-sensitive” Area Postrema neurons. All seven neurons tested showed no response to vasopressin after such V1 receptor blockade. These data suggest that there exists a population of Area Postrema neurons specifically responsive to circulating vasopressin as a result of actions of this peptide at V1 receptors. They also implicate these neurons in the physiological mechanisms through which circulating vasopressin acts in the Area Postrema to influence baroreceptor reflex sensitivity.
Makoto Funahashi - One of the best experts on this subject based on the ideXlab platform.
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presynaptically mediated effects of cholecystokinin 8 on the excitability of Area Postrema neurons in rat brain slices
Brain Research, 2015Co-Authors: Shingo Sugeta, Yoshiyuki Hirai, Hitoshi Maezawa, Nobuo Inoue, Yutaka Yamazaki, Makoto FunahashiAbstract:Cholecystokinin (CCK) is a well-known gut hormone that shows anorexigenic effects via action at peripheral and central receptors. CCK is also widely distributed throughout the mammalian brain and appears to function as a neurotransmitter and neuromodulator. The Area Postrema is one of the circumventricular organs, located on the dorsal surface of the medulla oblongata at the caudal end of the fourth ventricle. Blood vessels in the Area Postrema lack a blood brain barrier, offering specific central neural elements unique access to circulating substances. Immunohistochemical studies show CCK-A receptors in the Area Postrema, and we reported CCK-sensitive Area Postrema neurons. However, the receptive mechanism of CCK in Area Postrema neurons still remains unexplained. We investigated the responses of Area Postrema neurons to agonists and antagonists of CCK receptors using whole cell and perforated patch-clamp recordings in rat brain slices. The application of CCK-8 elicited excitatory responses, such as increases in the frequency of mEPSCs (miniature excitatory postsynaptic currents), a shift toward larger amplitude mEPSCs, and increases in the frequency of action potentials. These changes were found mostly in cells not displaying the hyperpolarization-activated cation current (Ih), except for small excitatory changes in a minority of Ih-positive neurons. Tonic inward currents or an inhibitory response to CCK-8 were never seen. Analysis of the amplitude of mEPSCs before and after the administration of CCK-8 indicated the responses mediated via the presynaptic receptors. The effect of CCK-8 was abolished in the presence of CNQX (AMPA type glutamate receptor antagonist). In the presence of lorglumide (a selective CCK-A receptor antagonist), CCK-8-induced excitatory responses were inhibited. No cells responded to the administration of non-sulfated CCK-8 (CCK-8NS, a selective CCK-B receptor agonist). We conclude that CCK-8 exerts its action via presynaptic CCK-A receptors to facilitate glutamate release onto Ih-negative Area Postrema cells.
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electrophysiologically identified presynaptic mechanisms underlying amylinergic modulation of Area Postrema neuronal excitability in rat brain slices
Brain Research, 2013Co-Authors: Takeshi Fukuda, Hitoshi Maezawa, Yoshiyuki Hirai, Yoshimasa Kitagawa, Makoto FunahashiAbstract:Abstract Amylin, which is co-secreted together with insulin by pancreatic beta cells, is considered to be an important peptide hormone involved in the control of feeding behavior and energy homeostasis. Although the Area Postrema has been implicated to be a primary target of amylin, there are no studies of the mechanisms by which amylin may alter the excitability of Area Postrema neurons. To investigate the mechanism for amylinergic modulation of neuronal excitability, we performed perforated patch-clamp recordings from Area Postrema neurons in rat brainstem slices. Amylin-induced changes in excitatory responses, such as increases in the frequency of mEPSCs (miniature excitatory postsynaptic currents) and changes in the amplitude distribution of mEPSCs, were found in cells not displaying the hyperpolarization-activated cation current (Ih). Area Postrema cells displaying Ih did not respond to amylin application. Inhibitory responses to amylin were never encountered. Bath application of CNQX (AMPA type glutamate receptor antagonist) abolished the effects of amylin. Depolarization of cells during amylin application was sufficient at 1 μM to cause action potential discharge by responding cells. We conclude that amylin receptors are located mostly on presynaptic glutamatergic terminals connecting to the Area Postrema neurons not displaying Ih and amylin concentrations can increase glutamate release enough to cause cell firing. Modulation of amylinergic activity may offer a novel target to influence food intake and obesity.
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The role of Area Postrema neurons expressing H-channels in the induction mechanism of nausea and vomiting.
Physiology & behavior, 2012Co-Authors: Keisuke Shinpo, Yoshiyuki Hirai, Hitoshi Maezawa, Yasunori Totsuka, Makoto FunahashiAbstract:The Area Postrema is one of the circumventricular organs, lacks a blood–brain barrier, and is well known as the chemoreceptor trigger zone for emesis. Area Postrema neurons are sensitive to emetic chemical substances carried in the blood plasma. Our previous study demonstrated the presence of 3 types of neurons characterized by different ion channels expressed in each cell type, but the type or types of Area Postrema neurons involved in the induction of nausea and/or emesis have remained unclear. To clarify the role of the most populous cells, which express the hyperpolarization-activated cation channel (H-channel), in induction of nausea and/or emesis, we investigated the effects of ZD7288 (an H-channel inhibitor) on apomorphine-induced conditioned taste aversion (CTA) to saccharin and c-Fos expression in the Area Postrema. We found that ZD7288 inhibited the acquisition of CTA and reduced apomorphine-induced c-Fos expression in the Area Postrema, indicating the involvement of the cells expressing H-channels in the induction of nausea and/or emesis. Finally, we discuss the role of cells expressing H-channels in the mechanism of nausea and/or vomiting.
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The sensitivity of hyperpolarization-activated cation current (Ih) to propofol in rat Area Postrema neurons.
Brain research, 2004Co-Authors: Makoto Funahashi, Yoshihiro Mitoh, Ryuji MatsuoAbstract:Area Postrema neurons mediate various autonomic responses, including emesis. We examined the effects of propofol, a widely used anesthetic with antiemetic properties, on the hyperpolarization-activated cation current (Ih) in rat Area Postrema neurons using a slice patch-clamp technique. Although propofol suppressed Ih of Area Postrema neurons in a dose-dependent manner that was similar to what we observed for the hippocampal CA1 neurons, the IC50 for Ih in Area Postrema neurons (38 microM) was more than six times less than that found for hippocampal CA1 neurons (235 microM). We conclude that rat Area Postrema neurons are exquisitely sensitive to propofol. Given that reductions of Ih are associated with decreased excitability in neurons, we believe that the known antiemetic effects of propofol anesthesia are at least partly a result of a direct action on Area Postrema neurons to lower their excitability.
Meredith Hay - One of the best experts on this subject based on the ideXlab platform.
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17β-Estradiol inhibits angiotensin II activation of Area Postrema neurons
American journal of physiology. Heart and circulatory physiology, 2003Co-Authors: Jaya Pamidimukkala, Meredith HayAbstract:It is well established that the Area Postrema, as a circumventricular organ, is susceptible to modulation by circulating hormones and peptides. Furthermore, activation of the Area Postrema has been...
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17-β-Estradiol Modulation of Area Postrema Potassium Currents
Journal of neurophysiology, 2000Co-Authors: Meredith HayAbstract:The purpose of this study was to determine the effects of 17-β-estradiol on Area Postrema neuronal activity in vivo and on Area Postrema potassium currents (IK) in vitro. In anesthetized rats, intr...
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AMPA receptor activation of Area Postrema neurons
The American journal of physiology, 1999Co-Authors: Meredith Hay, Kathy A. LindsleyAbstract:This study reports on the effects of activation of ionotropic glutamate receptors on Area Postrema neuron cytosolic calcium concentration ([Ca2+]i). In 140 of 242 Area Postrema neurons isolated fro...
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Area Postrema voltage-activated calcium currents.
Journal of neurophysiology, 1996Co-Authors: Meredith Hay, Eileen M. Hasser, Kathy A. LindsleyAbstract:1. Calcium currents in rabbit Area Postrema neurons were studied with the perforated patch-clamp technique. Experimental conditions eliminated Na+ and K+ currents and identified both low- and high-threshold voltage-activated calcium currents. 2. Low-threshold, T-type calcium currents were observed in 64% of the Area Postrema neurons recorded. This current activated near -60 mV and had an average peak amplitude of -36.2 +/- 5 pA (mean +/- SE) at -40 mV. This current began rapid inactivation near -95 mV, reached half-maximal inactivation at -71 mV and was totally inactivated by -40 mV. 3. A high-threshold transient current was recorded in all Area Postrema neurons, which consisted of both a transient and sustained component. This current was present at voltages greater than -40 mV and the transient component of this current was responsible for the majority of the total Ca2+ current. 4. Nickel ions (10 microM) effectively reduced both the T-type current and the high-threshold current. Cadmium ions (100 microM) effectively reduced the high-threshold current while having insignificant effects on the low-threshold current. 5. Application of the dihydropyridine antagonist nimodipine (1-10 microM) had no effect on either the low- or high-threshold voltage-activated calcium Ca2+ in Area Postrema neurons. In addition, application of omega-conotoxin-GVIA (2-10 microM) was also without effect on either the low- or high-threshold voltage-activated Ca2+ current, suggesting that Area Postrema neurons possess neither L- or N-type voltage-activated Ca2+ currents. 6. Application of omega-conotoxin MVIIC (10 microM) significantly inhibited the peak high-threshold Ca2+ current by 65.4% suggesting that Area Postrema neurons do possess a omega-conotoxin MVIIC-sensitive high-threshold Ca2+ channel. 7. Arg-vasopressin (150 nM) significantly increased the transient component of the high-threshold Ca2+ current but had little effect on either the low-threshold or the high-threshold sustained component.
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Membrane properties of Area Postrema neurons.
Brain Research, 1995Co-Authors: Meredith Hay, Kathy A. LindsleyAbstract:Abstract Intrinsic membrane properties, voltage-dependent sodium and voltage-dependent potassium currents of Area Postrema neurons in culture have been characterized with respect to their voltage dependence, time dependence and sensitivity to specific blocking agents. The Area Postrema is a hindbrain circumventricular organ which is known to have an important role in the central regulation of cardiovascular function. This study is the first to describe the biophysical properties of ion channels present in rat Area Postrema neurons. Recordings in current-clamp mode revealed a mean resting membrane potential of -55.0 ± 1.6 (n = 24) mV and an input resistance of 213.6 ± 23 M Ω. For the 24 neurons tested, the evoked action potential had a mean threshold of 38.8 ± 2 mV and a mean amplitude of 107.3 ± 15 mV. Our results show that the Area Postrema possesses only one principle sodium current which is completely abolished by 5 μM tetrodotoxin (TTX) (n = 28). This current activated near −50 mV and reached peak amplitude at −30 mV. The Area Postrema does not possess a TTX insensitive sodium current. The Area Postrema has at least two types of potassium currents. All Area Postrema neurons studied with tetraethylamonium (TEA) (n = 40) showed the presence of a slowly activating outward current which was present at voltages greater than −40 mV and was blocked by 10 mM TEA. In addition, 75% of the neurons studied (n = 30/40) also showed a rapidly inactivating, 4-AP sensitive IA type current which activated near −30 mV. Angiotensin II attenuated both the peak and the steady-state potassium currents, suggesting that angiotensin 11 may modulate Area Postrema activity by inhibiting voltage-gated potassium channels.
Ann C. Bonham - One of the best experts on this subject based on the ideXlab platform.
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Area Postrema-induced inhibition of the exercise pressor reflex.
American Journal of Physiology-Heart and Circulatory Physiology, 1997Co-Authors: Stefanie Bonigut, Ann C. Bonham, Charles L StebbinsAbstract:The exercise pressor reflex is opposed by the arterial baroreflex, and circulating peptides may act in the Area Postrema to enhance this inhibition. Therefore, we tested the hypothesis that the Area Postrema exerts an inhibitory effect on this reflex. Consequently, in six alpha-chloralose-anesthetized cats, blood pressure and heart rate responses to 30 s of electrically stimulated hindlimb contraction were compared before and after thermal coagulation of the Area Postrema. In six other cats, the same contraction-induced cardiovascular responses were assessed before and after chemical lesion of the Area Postrema using kainic acid (214 +/- 9 nl, 2.5-5 mM). Thermal lesion of the Area Postrema augmented blood pressure and heart rate responses to contraction from 29 +/- 5 to 47 +/- 7 mmHg (P < 0.05) and from 8 +/- 2 to 14 +/- 2 beats/min (P < 0.05), respectively. Chemical lesion of the Area Postrema enhanced contraction-evoked blood pressure (30 +/- 7 vs. 47 +/- 6 mmHg, P < 0.05) and heart rate (12 +/- 4 vs. 17 +/- 4 beats/min, P < 0.05) responses. These data suggest that the Area Postrema attenuates the exercise pressor reflex, possibly through the actions of circulating peptides on baroreflex function.
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Area Postrema and aortic or vagal afferents converge to excite cells in nucleus tractus solitarius
American Journal of Physiology-Heart and Circulatory Physiology, 1993Co-Authors: Ann C. Bonham, E M HasserAbstract:Area Postrema neurons enhance baroreflex function, perhaps by augmenting baroreceptor afferent processing in the nucleus tractus solitarius (NTS). If so, NTS neurons should receive convergent excitatory inputs from Area Postrema neurons and baroreceptors. The aims of this study were to record extracellular activity of NTS neurons to determine whether 1) Area Postrema and aortic baroreceptor afferents converged in NTS, 2) Area Postrema and vagal afferents converged in NTS, and 3) the convergent inputs were facilitative. Studies were performed in pentobarbital sodium- or alpha-chloralose-anesthetized rabbits. Forty-six of 194 NTS neurons received inputs from the Area Postrema and aortic depressor nerve. Twelve of the 23 inputs showed facilitative summation; unit response rate evoked by paired inputs (79%) doubled the predicted (calculated) response rate for simple addition (37%). Fifty-eight of 114 NTS neurons received excitatory inputs from the Area Postrema and vagus. Eleven of the 13 inputs showed facilitative summation; unit response to paired inputs (87%) doubled the predicted response (44%). Area Postrema neurons may augment the processing of aortic and vagal inputs by NTS neurons and, hence, enhance the reflex output of these afferent pathways.
Klaus-peter Ossenkopp - One of the best experts on this subject based on the ideXlab platform.
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Toxin-induced conditioned changes in taste reactivity and the role of the chemosensitive Area Postrema.
Neuroscience and biobehavioral reviews, 1995Co-Authors: Klaus-peter Ossenkopp, Lisa A. EckelAbstract:Conditioned taste avoidances (CTAs) are an important component of behavioral regulation of ingestion. In the laboratory CTAs can be produced by pairing a novel taste stimulus with the physiological feedback produced by a toxin, such as lithium. Such toxins putatively activate a chemosensitive brainstem structure, the Area Postrema, which ultimately results in the production of a CTA. The present review describes a series of studies which examined conditioned changes in taste reactivity responses (TRRs) when a novel intraoral sucrose taste was paired with the effects of an intraperitoneal (IP) injection of LiCl, and the role of the Area Postrema in the formation of conditioned palatability shifts. It was first of all necessary to examine the effects of Area Postrema ablations on TRRs to a range of intraoral sucrose and quinine stimulus intensities. In the first study Area Postrema lesioned rats exhibited concentration dependent changes in TRRs to these taste stimuli that were very similar to those exhibited by sham lesioned rats. The second study demonstrated that 30 s intraoral infusions of sucrose (0.3 M), presented at 5 or 10 min intervals following an IP injection of LiCl (3.0 meq), resulted in conditioned changes in TRRs. These were characterized by orderly, gradual reductions in ingestive responses and increases in aversive responses. Finally, when Area Postrema lesioned rats (Study 3) were subjected to this conditioning procedure (brief sucrose presentations paired with the effects of LiCl) no evidence for conditioned or unconditioned changes in TRRs to sucrose were obtained. Lesioned rats injected with LiCl behaved similarly to sham lesioned rats injected with NaCl. These series of studies provide evidence indicating that the chemosensitive Area Postrema mediates the formation of conditioned palatability shifts induced by treatment with a toxin such as lithium.
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Deoxynivalenol (vomitoxin)-induced conditioned taste aversions in rats are mediated by the chemosensitive Area Postrema
Pharmacology Biochemistry and Behavior, 1994Co-Authors: Klaus-peter Ossenkopp, Maurice Hirst, William A. RapleyAbstract:The present experiments used a conditioned aversion to a novel saccharin taste to assess the aversive effects of deoxynivalenol (vomitoxin) administration, and to examine the putative mediating role of the chemosensitive Area Postrema (AP). In experiment 1 adult male rats drank a novel 0.15% saccharin solution followed by injection of deoxynivalenol (n = 7; 0.125 mg/kg, IP) or vehicle (n = 7; propylene glycol, 0.5 mg/kg). In subsequent two-bottle preference tests the rats conditioned with deoxynivalenol displayed significantly (p < 0.01) lower absolute and relative saccharin intake levels in comparison to control rats which exhibited a strong preference for saccharin solution. In experiment 2 adult male rats received Area Postrema ablations (n = 6) or sham lesions (n = 6). On two conditioning days all rats drank a novel 0.15% saccaharin solution followed by injections of deoxynivalenol (0.125 mg/kg, IP). In subsequent two-bottle preference tests the sham-lesioned rats displayed a significant (p < 0.01) aversion to the saccharin stimulus, relative to the Area Postrema-ablated rats which exhibited a preference for the saccharin solution. Thus, systemic administration of deoxynivalenol, following a novel taste, induced conditioned taste aversions which were mediated by the Area Postrema.