Oksitosin Nöronlarında Kainat Reseptör Alt Birimlerinin Sentezi: İmmünohistokimyasal Çalışma
Yıl 2020,
Cilt: 46 Sayı: 3, 357 - 363, 01.12.2020
Zehra Minbay
,
Özhan Eyigör
Öz
Oksitosin nöronları, gebe dişide doğumu başlatan ve sürdüren, ayrıca meme bezlerinden süt enjeksiyonunu sağlayan nöroendokrin mekanizmanın en önemli kısmını oluştururlar. Hipotalamik supraoptik (SON) ve paraventriküler (PVN) çekirdeklerde yerleşik olan bu nöronların regülasyonunda merkezi sinir sisteminde yer alan glutamaterjik sistemin önemli rolü olduğu bilinmektedir. Glutamat etkisini hücre membranları üzerinde bulunan reseptörlerine bağlanıp onları aktive ederek gösterir. Bu reseptörlerin üç ayrı alt grubundan biri olan kainat reseptörlerine ait alt birim proteinlerinin oksitosin nöronlarınca sentezlendiğine dair bilgi henüz raporlanmamıştır. Bu çalışmada, oksitosin nöronlarında kainat reseptör alt birimlerinin (GluK1, GluK2, GluK3, GluK5) eksprese edilip edilmediğinin belirlenmesi amaçlandı. Bu amaçla dişi sıçan hipotalamusunda oksitosin ve reseptör ko-lokalizasyonunun belirlenmesinde ikili immünofloresan işaretleme tekniği kullanıldı. Bu boyamaların sonucunda, SON ve PVN’deki oksitosin nöronlarının sayıca çok büyük bir kısmının aynı zamanda GluK5 proteini sentezledikleri belirlendi. Her iki çekirdekte yer alan tüm oksitosin nöronlarının yaklaşık yarısının GluK2 sentezlendiği görüldü. Preparatların incelenmesi sonucunda oksitosin nöronlarında GluK1 ve GluK3 proteinlerinin ekspresyonu izlenmedi. Sonuç olarak çalışmamızda oksitosin nöronlarının fonksiyonel reseptör kanalı oluşturabilecek kainat reseptör alt birimleri eksprese ettiklerinin belirlenmesi, endojen glutamatın oksitosin nöronları üzerindeki etkilerini bu reseptörlere bağlanarak gerçekleştirebileceğini düşündürmektedir. Oksitosin nöronlarında kainat reseptör alt birimlerinin ekspresyonun gösterilmesi bu konudaki literatüre önemli katkılar sağlayacağı ön görüsündeyiz. Gelecekte yapılacak olan fizyolojik ve farmakolojik çalışmalarla veya transgenik hayvanlardan elde edilebilecek bulgulara çalışmamızda elde ettiğimiz sonuçlar eklendiğinde, kainat reseptörlerinin oksitosin sentez ve salgılama mekanizmasındaki rolü açıklığa kavuşacaktır.
Destekleyen Kurum
TÜBİTAK
Teşekkür
Bu çalışma TÜBİTAK tarafından desteklenmiştir (101S058 [SBAG–2459]). GluK5 antikoru için Prof Dr. Lothar JENNES’e (University of Kentucky) ve lazer taramalı konfokal mikroskop kullanımımızı sağlayan Kentucky Üniversitesi Görüntüleme Ünitesi sorumlusu Prof. Dr. Bruce MALEY’e teşekkür ederiz.
Kaynakça
- Challis JRG, Lye SJ. Parturition. In: The physiology of reproduction. Knobil E, Neill JD (eds). New York: Raven Press;1994. 985-1031.
- Higuchi T, Okere CO. Role of Supraoptic nucleus in regulation of parturition and milk ejection revisited. Microsc Res Tech 2002;56:113-121.
- Wakerley JB, Clarke G, Summerlee AJ. Milk ejection and its control. In: The physiology of reproduction. Knobil E, Neill JD (eds). New York: Raven Press; 1994. 1131-1177.
- Gainer H, Wray S. Cellular and molecular biology of oxytocin and vasopressin. In: The physiology of reproduction. Knobil E, Neill JD (eds). New York: Raven Press; 1994.1099-1129.
- Hatton GI. Emerging concepts of structure-function dynamics in adult brain: the hypothalamo-neurohypophysial system. Prog Neurobiol 1990;34:437-504.
- Hollmann M, Heinemann S. Cloned glutamate receptors. Ann Rev Neurosci 1994;17:31-108.
- Daftary SS, Boudaba C, Szabó K, Tasker JG. Noradrenergic excitation of magnocellular neurons in the rat hypothalamic paraventricular nucleus via intranuclear glutamatergic circuits. J Neurosci 1998;18:10619-10628.
- Bealer SL, Crowley WR. Stimulation of central and systemic oxytocin release by histamine in the paraventricular hypothalamic nucleus: Evidence for an interaction with norepinephrine,. Endocrinology 1999;140:1158-1164.
- Gribkoff VK. Electrophysiological evidence for N-methyl-D-aspartate excitatory amino acid receptors in the rat supraoptic nucleus in vitro. Neurosci Lett 1991;131:260-262.
- Inenaga K, Honda E, Hirakawa T, Nakamura S, Yamashita H. Glutamatergic synaptic inputs to mouse supraoptic neurons in calcium-free medium in vitro. J Neuroendocrinol, 1998;10:1-7.
- Meeker RB, Greenwood RS, Hayward JN. Glutamate is the major excitatory transmitter in the supraoptic nuclei. Ann NY Acad Sci 1993;22: 636-639.
- Van Den Pol AN, Trombley PQ. Glutamate neurons in hypothalamus regulate excitatory transmission. J Neurosci 1993;13:2829-2836.
- Van Den Pol AN, Wuarin JP, Dudek F.E. Glutamate neurotransmission in the neuroendocrine hypothalamus. In: Excitatory Amino Acids The Role in Neuroendocrine Function. Brann DW, Mahesh B, (eds). Boca Raton: CRC Press; 1996. 1-54.
- Voisin DL, Herbison AE, Chapman C, Poulain DA. Effects of central GABAB receptor modulation upon the milk ejection reflex in the rat. Neuroendocrinology 1996;63:368-376.
- Brann DW. Glutamate: A major excitatory transmitter in neuroendocrine regulation. Neuroendocrinology 1995;61:213-225.
- Brann DW, Mahesh VB. Excitatory amino acids: Function and significance in reproduction and neuroendocrine regulation. Front Neuroendocrinol 1994;15:3-49.
- Seeburg PH. The molecular biology of mammalian glutamate receptor channels. Trends Neurosci 1993;16:359-365.
- Bettler B, Mulle C. Review: neurotransmitter receptors II. AMPA and kainate receptors. Neuropharmacology 1995;34: 123-139.
- Meeker RB, Swanson DJ, Greenwood RS, Hayward JN. Quantitative mapping of glutamate presynaptic terminals in the supraoptic nucleus and surrounding hypothalamus. Brain Res 1993;600:112-122.
- Jourdain P, Dupouy B, Bonhomme R, Theodosis DT, Poulain DA, Israel JM. Electrophysiological studies of oxytocin neurons in organotypic slice cultures. Adv Exp Med Biol 1998;449:135-145.
- Minbay FZ, Eyigor O, Cavusoğlu I. Kainic acid activates oxytocinergic neurons through non-nmda glutamate receptors. Int J Neurosci 2006;116:587-600.
- Stern JE, Galarreta M, Foehring RC, Hestrin S, Armstrong WE. Differences in the properties of ionotropic glutamate synaptic currents in oxytocin and vasopressin neuroendocrine neurons. J Neurosci 1999;19:2267-3375.
- Parker SL, Crowley WR. Central stimulation of oxytocin release in the lactating rat by N-methyl-D-aspartate: Requirement for coactivation through non-NMDA glutamate receptors or the glycine coagonist site. Neuroendocrinology 1995;62:467-478.
- Parker SL, Crowley WR. Stimulation of oxytocin release in the lactating rat by central excitatory amino acid mechanisms: evidence for specific involvement of R,S-α-amino-3-hydroxy-5-methylisoxazole-4-propionic acid-sensitive glutamate receptors. Endocrinology 1993;133:2847-2854.
- Jourdain P, Israel JM, Dupouy B, Oliet SH, Allard M, Vitiello S, Theodosis DT, Poulain DA. Evidence for a hypothalamic oxytocin-sensitive pattern-generating network governing oxytocin neurons in vitro. J Neurosci 1998;18:6641-6649.
- Olazabal DE, Ferreira A. Maternal behavior in rats with kainic acid-induced lesions of the hypothalamic paraventricular nucleus. Physiol Behav 1997;61:779-784.
- Richardson CM, Wakerley JB. Glutamate excitation of oxytocin neurons in vitro involves predominantly non-NMDA receptors. Brain Res 1997;767:158-161.
- Yagi K, Onaka T, Yoshida A. Role of N-methyl-D-aspartate (NMDA) receptors in vasopressin and oxytocin responses to emotional stimuli. Adv Exp Med Biol 1998;449:131-134.
- Israel JM, Poulain DA. 17-Oestradiol modulates in vitro electrical properties and responses to kainate of oxytocin neurones in lactating rats. J Physiol (Lond) 2000;15:457-470.
- Sun Q, Pretel S, Applegate CD, Piekut DT. Oxytocin and vasopressin mRNA expression in rat hypothalamus following kainic acid-induced seizures. Neuroscience 1996;71:543-554.
- Ginsberg SD, Price DL, Blackstone CD, Huganir RL, Martin LJ. The AMPA glutamate receptor GluR3 is enriched in oxytocinergic magnocellular neurons and is localized at synapses. Neuroscience 1995;65:563-575.
- Curras-Collazo MC, Chin C, Diaz G, Stivers C, Bozzetti L, Tran LY. Immunolabeling reveals cellular localization of the N-methyl-D-aspartate receptor subunit NR2B in neurosecretory cells but not astrocytes of the rat magnocellular nuclei. J Comp Neurol 2000;427:93-108.
- Swanson LW. Brain Maps: Structure of the rat brain. Amsterdam: Elsevier; 1998.
- Jirikowski GF, Caldwell JD, Pikgrim C, Stumpf WE, Pedersen CA. Changes in immunostaining for oxytosin in the forebrain of the female rat during late pregnancy, parturition and early lactation. Cell Tissue Res 1980;256:411-417.
- Eyigor O, Centers A, Jennes L. Distribution of ionotropic glutamate receptor subunit mRNAs in the rat hypothalamus. J Comp Neurol 2001;434:101-124.
- Herman JP, Eyigor O, Ziegler DR, Jennes L. Expression of ionotropic glutamate receptor subunit mRNAs in the hypothalamic paraventricular nucleus of the rat. J Comp Neurol 2000;422:352-362.
- Petrelia RS, Wang YX, Wenthold RJ. Histological and ultrastructural localization of the kainate receptor subunits, KA2 and GluR6/7, in the rat nervous system using selective antipeptide antibodies. J Comp Neurol 1994;349:85-110.
- Van Den Pol AN, Hermans-Borgmeyer I, Hofer M, Ghosh P, Heinemann S. Ionotropic glutamate-receptor gene expression in hypothalamus: Localization of AMPA, kainate, and NMDA receptor RNA with in situ hybridization. J Comp Neurol 1994;343:428-444.
- Crowley WR, Armstrong WE. Neurochemical regulation of oxytocin secretion in lactation. Endocr Rev 1992;13:33-65.
- Pak CW, Curras-Collazo MC. Expression and plasticity of glutamate receptors in the supraoptic nucleus of hypothalamus. Microsc Res Tech 2002;56:92-100.
- Boudaba C, Schrader LA, Tasker JG. Physiological evidence for local excitatory synaptic circuits in the rat hypothalamus. J Neurophysiol 1997;77:3396-3400.
- Van Den Pol AN, Wuarin JP, Dudek FE. Glutamate, the dominant excitatory transmitter in neuroendocrine regulation. Science 1990;250:1276-1278.
- El Majdoubi M, Poulain DA, Theodosis DT. The glutamatergic innervation of oxytocin- and vasopressin-secreting neurons in the rat supraoptic nucleus and its contribution to lactation-induced synaptic plasticity. Eur J Neurosci 1996;8:1377-1389.
- Theodosis DT, El Majdoubi M, Gies U, Poulain DA. Physiologically-linked structural plasticity of inhibitory and excitatory synaptic inputs to oxytocin neurons. Adv Exp Med Biol 1995;395:155-171.
- Cui C, Mayer ML. Heteromeric kainate receptors formed by coassembly of GluR5, GluR6, and GluR7. J Neurosci 1999;19:8281-8291.
- Meeker RB, Greenwood RS, Hayward JN. Glutamate receptors in the rat hypothalamus and pituitary. Endocrinology 1994;134:621-629.
- Wuarin JP, Dudek FE. Patch-clamp analysis of spontaneous synaptic currents in supraoptic neuroendocrine cells of the rat hypothalamus. J Neurosci 1993;13:2323-2331.
- Yang QZ, Smithson KG, Hatton GI. NMDA and non-NMDA receptors on rat supraoptic nucleus neurons activated monosynaptically by olfactory afferents. Brain Res 1995;680:207-216.
- Gribkoff VK, Dudek FE. Effects of excitatory amino acid antagonists on synaptic responses of supraoptic neurons in slices of rat hypothalamus. J Neurophysiol 1990;63:60-71.
- Nissen R, Hu B, Renaud LP. N-methyl-D-aspartate receptor antagonist ketamine selectively attenuates spontaneous phasic activity of supraoptic vasopressin neurons in vivo. Neuroscience 1994;59:115-120.
- Nissen R, Hu B, Renaud LP. Regulation of spontaneous phasic firing of rat supraoptic vasopressin neurons in vivo by glutamate receptors. J Physiol 1995;484:415-424.
Synthesis of Kainate Receptor Subunits in Oxytocin Neurons: An Immunohistochemical Study
Yıl 2020,
Cilt: 46 Sayı: 3, 357 - 363, 01.12.2020
Zehra Minbay
,
Özhan Eyigör
Öz
Oxytocin neurons are the most important part of the neuroendocrine mechanism which starts and maintains the parturition as well as the milk ejection. These neurons are localized in the hypothalamic supraoptic (SON) and paraventricular (PVN) nuclei and glutamatergic system plays an important role in the regulation of these neurons in the central nervous system. Glutamate exerts its effects by binding and activating its receptors on the plasma membrane. There is a lack of knowledge in the literature on the synthesis of kainate receptors, as one of the glutamatergic subfamilies, by oxytocin neurons. In this study the aim is to determine if the kainate receptor subunits (GluK1, GluK2, GluK3, GluK5) were expressed in oxytocin neurons. For this purpose, double immunofluorescence labeling technique was employed in order to assess the co-localization of oxytocin with respective receptor in the female rat hypothalamus. The results of this staining showed that almost the vast majority of oxytocin neurons were immuno-reactive for GluK5 protein in both SON and PVN. It was determined that almost half of the oxytocin neurons in both of the nuclei synthesize GluK2. Analyses of the preparations revealed no expression of GluK1 and GluK3 proteins in the oxytocin neurons. As a result, the determination of the oxytocin neurons can synthesize kainate receptor subunits which can form functional kainate receptor channels suggests that the endogenous glutamate can exert its effects on oxytocin neurons by binding these receptors. We anticipate that showing the oxytocin neurons express kainate receptor subunits would be an important addition to the literature. The future physiological and/or pharmacological studies as well as the possible findings from the transgenic animals would enlighten the role of kainate receptors in the regulation of oxytocin synthesis and/or releasing mechanism.
Kaynakça
- Challis JRG, Lye SJ. Parturition. In: The physiology of reproduction. Knobil E, Neill JD (eds). New York: Raven Press;1994. 985-1031.
- Higuchi T, Okere CO. Role of Supraoptic nucleus in regulation of parturition and milk ejection revisited. Microsc Res Tech 2002;56:113-121.
- Wakerley JB, Clarke G, Summerlee AJ. Milk ejection and its control. In: The physiology of reproduction. Knobil E, Neill JD (eds). New York: Raven Press; 1994. 1131-1177.
- Gainer H, Wray S. Cellular and molecular biology of oxytocin and vasopressin. In: The physiology of reproduction. Knobil E, Neill JD (eds). New York: Raven Press; 1994.1099-1129.
- Hatton GI. Emerging concepts of structure-function dynamics in adult brain: the hypothalamo-neurohypophysial system. Prog Neurobiol 1990;34:437-504.
- Hollmann M, Heinemann S. Cloned glutamate receptors. Ann Rev Neurosci 1994;17:31-108.
- Daftary SS, Boudaba C, Szabó K, Tasker JG. Noradrenergic excitation of magnocellular neurons in the rat hypothalamic paraventricular nucleus via intranuclear glutamatergic circuits. J Neurosci 1998;18:10619-10628.
- Bealer SL, Crowley WR. Stimulation of central and systemic oxytocin release by histamine in the paraventricular hypothalamic nucleus: Evidence for an interaction with norepinephrine,. Endocrinology 1999;140:1158-1164.
- Gribkoff VK. Electrophysiological evidence for N-methyl-D-aspartate excitatory amino acid receptors in the rat supraoptic nucleus in vitro. Neurosci Lett 1991;131:260-262.
- Inenaga K, Honda E, Hirakawa T, Nakamura S, Yamashita H. Glutamatergic synaptic inputs to mouse supraoptic neurons in calcium-free medium in vitro. J Neuroendocrinol, 1998;10:1-7.
- Meeker RB, Greenwood RS, Hayward JN. Glutamate is the major excitatory transmitter in the supraoptic nuclei. Ann NY Acad Sci 1993;22: 636-639.
- Van Den Pol AN, Trombley PQ. Glutamate neurons in hypothalamus regulate excitatory transmission. J Neurosci 1993;13:2829-2836.
- Van Den Pol AN, Wuarin JP, Dudek F.E. Glutamate neurotransmission in the neuroendocrine hypothalamus. In: Excitatory Amino Acids The Role in Neuroendocrine Function. Brann DW, Mahesh B, (eds). Boca Raton: CRC Press; 1996. 1-54.
- Voisin DL, Herbison AE, Chapman C, Poulain DA. Effects of central GABAB receptor modulation upon the milk ejection reflex in the rat. Neuroendocrinology 1996;63:368-376.
- Brann DW. Glutamate: A major excitatory transmitter in neuroendocrine regulation. Neuroendocrinology 1995;61:213-225.
- Brann DW, Mahesh VB. Excitatory amino acids: Function and significance in reproduction and neuroendocrine regulation. Front Neuroendocrinol 1994;15:3-49.
- Seeburg PH. The molecular biology of mammalian glutamate receptor channels. Trends Neurosci 1993;16:359-365.
- Bettler B, Mulle C. Review: neurotransmitter receptors II. AMPA and kainate receptors. Neuropharmacology 1995;34: 123-139.
- Meeker RB, Swanson DJ, Greenwood RS, Hayward JN. Quantitative mapping of glutamate presynaptic terminals in the supraoptic nucleus and surrounding hypothalamus. Brain Res 1993;600:112-122.
- Jourdain P, Dupouy B, Bonhomme R, Theodosis DT, Poulain DA, Israel JM. Electrophysiological studies of oxytocin neurons in organotypic slice cultures. Adv Exp Med Biol 1998;449:135-145.
- Minbay FZ, Eyigor O, Cavusoğlu I. Kainic acid activates oxytocinergic neurons through non-nmda glutamate receptors. Int J Neurosci 2006;116:587-600.
- Stern JE, Galarreta M, Foehring RC, Hestrin S, Armstrong WE. Differences in the properties of ionotropic glutamate synaptic currents in oxytocin and vasopressin neuroendocrine neurons. J Neurosci 1999;19:2267-3375.
- Parker SL, Crowley WR. Central stimulation of oxytocin release in the lactating rat by N-methyl-D-aspartate: Requirement for coactivation through non-NMDA glutamate receptors or the glycine coagonist site. Neuroendocrinology 1995;62:467-478.
- Parker SL, Crowley WR. Stimulation of oxytocin release in the lactating rat by central excitatory amino acid mechanisms: evidence for specific involvement of R,S-α-amino-3-hydroxy-5-methylisoxazole-4-propionic acid-sensitive glutamate receptors. Endocrinology 1993;133:2847-2854.
- Jourdain P, Israel JM, Dupouy B, Oliet SH, Allard M, Vitiello S, Theodosis DT, Poulain DA. Evidence for a hypothalamic oxytocin-sensitive pattern-generating network governing oxytocin neurons in vitro. J Neurosci 1998;18:6641-6649.
- Olazabal DE, Ferreira A. Maternal behavior in rats with kainic acid-induced lesions of the hypothalamic paraventricular nucleus. Physiol Behav 1997;61:779-784.
- Richardson CM, Wakerley JB. Glutamate excitation of oxytocin neurons in vitro involves predominantly non-NMDA receptors. Brain Res 1997;767:158-161.
- Yagi K, Onaka T, Yoshida A. Role of N-methyl-D-aspartate (NMDA) receptors in vasopressin and oxytocin responses to emotional stimuli. Adv Exp Med Biol 1998;449:131-134.
- Israel JM, Poulain DA. 17-Oestradiol modulates in vitro electrical properties and responses to kainate of oxytocin neurones in lactating rats. J Physiol (Lond) 2000;15:457-470.
- Sun Q, Pretel S, Applegate CD, Piekut DT. Oxytocin and vasopressin mRNA expression in rat hypothalamus following kainic acid-induced seizures. Neuroscience 1996;71:543-554.
- Ginsberg SD, Price DL, Blackstone CD, Huganir RL, Martin LJ. The AMPA glutamate receptor GluR3 is enriched in oxytocinergic magnocellular neurons and is localized at synapses. Neuroscience 1995;65:563-575.
- Curras-Collazo MC, Chin C, Diaz G, Stivers C, Bozzetti L, Tran LY. Immunolabeling reveals cellular localization of the N-methyl-D-aspartate receptor subunit NR2B in neurosecretory cells but not astrocytes of the rat magnocellular nuclei. J Comp Neurol 2000;427:93-108.
- Swanson LW. Brain Maps: Structure of the rat brain. Amsterdam: Elsevier; 1998.
- Jirikowski GF, Caldwell JD, Pikgrim C, Stumpf WE, Pedersen CA. Changes in immunostaining for oxytosin in the forebrain of the female rat during late pregnancy, parturition and early lactation. Cell Tissue Res 1980;256:411-417.
- Eyigor O, Centers A, Jennes L. Distribution of ionotropic glutamate receptor subunit mRNAs in the rat hypothalamus. J Comp Neurol 2001;434:101-124.
- Herman JP, Eyigor O, Ziegler DR, Jennes L. Expression of ionotropic glutamate receptor subunit mRNAs in the hypothalamic paraventricular nucleus of the rat. J Comp Neurol 2000;422:352-362.
- Petrelia RS, Wang YX, Wenthold RJ. Histological and ultrastructural localization of the kainate receptor subunits, KA2 and GluR6/7, in the rat nervous system using selective antipeptide antibodies. J Comp Neurol 1994;349:85-110.
- Van Den Pol AN, Hermans-Borgmeyer I, Hofer M, Ghosh P, Heinemann S. Ionotropic glutamate-receptor gene expression in hypothalamus: Localization of AMPA, kainate, and NMDA receptor RNA with in situ hybridization. J Comp Neurol 1994;343:428-444.
- Crowley WR, Armstrong WE. Neurochemical regulation of oxytocin secretion in lactation. Endocr Rev 1992;13:33-65.
- Pak CW, Curras-Collazo MC. Expression and plasticity of glutamate receptors in the supraoptic nucleus of hypothalamus. Microsc Res Tech 2002;56:92-100.
- Boudaba C, Schrader LA, Tasker JG. Physiological evidence for local excitatory synaptic circuits in the rat hypothalamus. J Neurophysiol 1997;77:3396-3400.
- Van Den Pol AN, Wuarin JP, Dudek FE. Glutamate, the dominant excitatory transmitter in neuroendocrine regulation. Science 1990;250:1276-1278.
- El Majdoubi M, Poulain DA, Theodosis DT. The glutamatergic innervation of oxytocin- and vasopressin-secreting neurons in the rat supraoptic nucleus and its contribution to lactation-induced synaptic plasticity. Eur J Neurosci 1996;8:1377-1389.
- Theodosis DT, El Majdoubi M, Gies U, Poulain DA. Physiologically-linked structural plasticity of inhibitory and excitatory synaptic inputs to oxytocin neurons. Adv Exp Med Biol 1995;395:155-171.
- Cui C, Mayer ML. Heteromeric kainate receptors formed by coassembly of GluR5, GluR6, and GluR7. J Neurosci 1999;19:8281-8291.
- Meeker RB, Greenwood RS, Hayward JN. Glutamate receptors in the rat hypothalamus and pituitary. Endocrinology 1994;134:621-629.
- Wuarin JP, Dudek FE. Patch-clamp analysis of spontaneous synaptic currents in supraoptic neuroendocrine cells of the rat hypothalamus. J Neurosci 1993;13:2323-2331.
- Yang QZ, Smithson KG, Hatton GI. NMDA and non-NMDA receptors on rat supraoptic nucleus neurons activated monosynaptically by olfactory afferents. Brain Res 1995;680:207-216.
- Gribkoff VK, Dudek FE. Effects of excitatory amino acid antagonists on synaptic responses of supraoptic neurons in slices of rat hypothalamus. J Neurophysiol 1990;63:60-71.
- Nissen R, Hu B, Renaud LP. N-methyl-D-aspartate receptor antagonist ketamine selectively attenuates spontaneous phasic activity of supraoptic vasopressin neurons in vivo. Neuroscience 1994;59:115-120.
- Nissen R, Hu B, Renaud LP. Regulation of spontaneous phasic firing of rat supraoptic vasopressin neurons in vivo by glutamate receptors. J Physiol 1995;484:415-424.