PT  - JOURNAL ARTICLE
AU  - Shabrine S. Daftary
AU  - Cherif Boudaba
AU  - Kriszta Szabó
AU  - Jeffrey G. Tasker
TI  - Noradrenergic Excitation of Magnocellular Neurons in the Rat Hypothalamic Paraventricular Nucleus via Intranuclear Glutamatergic Circuits
AID  - 10.1523/JNEUROSCI.18-24-10619.1998
DP  - 1998 Dec 15
TA  - The Journal of Neuroscience
PG  - 10619--10628
VI  - 18
IP  - 24
4099  - http://www.jneurosci.org/content/18/24/10619.short
4100  - http://www.jneurosci.org/content/18/24/10619.full
SO  - J. Neurosci.1998 Dec 15; 18
AB  - Noradrenergic projections to the hypothalamus play a critical role in the afferent control of oxytocin and vasopressin release. Recent evidence for intrahypothalamic glutamatergic circuits prompted us to test the hypothesis that the excitatory effect of noradrenergic inputs on oxytocin and vasopressin release is mediated in part by local glutamatergic interneurons. The voltage response to norepinephrine (30–300 μm) was tested with whole-cell recordings in putative magnocellular neurons of the paraventricular nucleus (PVN) in hypothalamic slices (400 μm). Norepinephrine elicited an α1 receptor-mediated direct depolarization in 23% of the magnocellular neurons tested; however, the most prominent response, seen in 42% of the magnocellular neurons, was an α1receptor-mediated increase in the frequency of EPSPs. The norepinephrine-induced increase in EPSPs was blocked by tetrodotoxin and by ionotropic glutamate receptor antagonists, suggesting that norepinephrine excited presynaptic glutamate neurons to cause an increase in spike-mediated transmitter release. The increase in EPSPs also was observed in a surgically isolated PVN preparation (64% of cells) and with microdrop applications of norepinephrine (1 mm, 33% of cells) and glutamate (0.5–1 mm, 28%) in the PVN, indicating that the norepinephrine-sensitive presynaptic glutamate neurons are located within the PVN. Biocytin injection and subsequent immunohistochemical labeling revealed that both oxytocin and vasopressin neurons responded to norepinephrine. Our data indicate that magnocellular neurons of the PVN receive excitatory inputs from intranuclear glutamatergic neurons that express α1-adrenoreceptors. These glutamatergic interneurons may serve as an excitatory relay in the afferent noradrenergic control of oxytocin and vasopressin release under certain physiological conditions.