Submitted on January 28, 2008
Accepted on August 8, 2008
Heterogeneous Distribution of Basal Cyclic Guanosine Monophosphate (cGMP) within Distinct Neuronal Populations in the Hypothalamic Paraventricular Nucleus
Kellysan Powers-Martin1, Jacqueline K. Phillips1, Vinicia C Biancardi2, and Javier E Stern2*
1 Division of Health Science, Murdoch University, Perth, Australia; State Agricultural Biotechnology Centre, Murdoch University, Perth, Western Australia, Australia
2 Physiology, Medical College of Georgia, Augusta, Georgia, United States
* To whom correspondence should be addressed. E-mail: jstern{at}mcg.edu.
The supraoptic (SON) and the paraventricular (PVN) hypothalamic nuclei constitute major neuronal substrates underlying nitric oxide (NO) effects on autonomic and neuroendocrine control. Within these nuclei, constitutively produced NO restrains the firing activity of magnocellular neurosecretory and preautonomic neurons, actions thought to be mediated by a cGMP-dependent enhancement of GABAergic inhibitory transmission. In the present study, we expanded on this knowledge by performing a detailed anatomical characterization of constitutive NO-receptive, cGMP-producing neurons within the PVN. To this end, we combined tract tracing techniques and immunohistochemistry to visualize cGMP immunoreactivity within functionally, neurochemically and topographically discrete PVN neuronal populations in Wistar rats. Basal cGMP immunoreactivity was readily observed in the PVN, both in neuronal and vascular profiles. The incidence of cGMP immunoreactivity was significantly higher in magnocellular (69%) when compared to preautonomic (~10%) neuronal populations (P < 0.01). No differences were observed between oxytocin (OT) and vasopressin (VP) magnocellular neurons. In preautonomic neurons, the incidence of cGMP was independent on their subnuclei distribution, innervated target (i.e., intermedilateral cell column, nucleus tractus solitarii or rostral ventrolateral medulla) or their neurochemical phenotype (i.e., OT or VP). Finally, high levels of cGMP immunoreactivity were observed in GABAergic somata and terminals within the PVN of eGFP-GAD67 transgenic mice. Altogether, these data support a highly heterogeneous distribution of basal cGMP levels within the PVN, and further support the notion that constitutive NO actions in the PVN involve intricate cell-cell interactions as well as heterogeneous signalling modalities.
