Norepinephrine actions on the electrical properties of identified hypothalamic paraventricular nucleus neurons
Description
The paraventricular nucleus (PVN) of the hypothalamus is a heterogeneous structure made up of two general populations of cells, the magnocellular and parvocellular neurons, each of which is further divided into subpopulations of cells. The magnocellular neurons are comprised of oxytocin- and vasopressin-secreting neurons, and the parvocellular neurons are made up of several types of neurosecretory and non-neurosecretory neurons. During electrophysiological recordings, magnocellular (type I) and parvocellular (type II) neurons of the PVN can be distinguished based on their electrical properties. Whereas magnocellular neurons are relatively homogenous in their membrane properties, parvocellular neurons display a wide range of electrical properties that may reflect their morphological and functional diversity. Conventional intracellular and whole-cell patch-clamp recordings in hypothalamic slices enabled me to identify six electrophysiologically distinct populations of neurons, which I refer to as types II A through II F. The most distinct electrophysiological characteristic was the variable expression of the low-threshold, Ca$\sp{2+}$-dependent spike (LTS). The neuronal subtypes either did not generate a LTS or generated LTSs of increasing amplitude and/or duration. The number of action potentials elicited by the different LTSs in these neurons ranged from a single spike to bursts of spikes. The parvocellular subtypes also exhibited varying degrees of inward rectification in their current-voltage relations and differed in their hyperpolarizing after potentials and membrane time constants Norepinephrine has been implicated in the secretion of virtually all the pituitary hormones, and is known to play a focal role in regulating the hypothalamoadenohypophysial/neurohypophysial axes. However, the sites at which the effects are exerted is largely unknown. Combined electrophysiological and histochemical double labeling techniques enabled me to study the regulation of identified PVN neurons by norepinephrine. The identity of recorded magnocellular and parvocellular neurons was verified anatomically with biocytin injection and subsequent immunohistochemical processing using antisera to oxytocin, vasopressin or the neurophysins. In putative magnocellular neurons, norepinephrine caused a direct, $\alpha\sb1$ adrenoreceptor-mediated depolarization in 23% of the cells and elicited an increase in the frequency of excitatory post-synaptic potentials (EPSPs) in another 38% of the recorded cells. The norepinephrine-induced increase in EPSPs was caused by $\alpha\sb1$-adrenoreceptor activation of intranuclear glutamate neurons since it was blocked by ionotropic glutamate receptor antagonists and persisted in a surgically isolated PVN. The norepinephrine-induced increase in EPSPs in magnocellular neurons appears to be specific to oxytocin neurons. In putative parvocellular neurons, norepinephrine induced a $\beta$ adrenoreceptor-mediated hyperpolarization in 14% of the neurons tested and an $\alpha\sb1$ adrenoreceptor-mediated increase in EPSPs in another 25% of the neurons. The norepinephrine-induced increase in EPSPs in parvocellular neurons was also mediated by intrahypothalamic glutamatergic interneurons, although it is not known whether these cells are located in the PVN. The norepinephrine-responsive parvocellular neurons corresponded to two or more electrophysiologically distinct subtypes of parvocellular neurons. These results suggest that norepinephrine has direct excitatory and inhibitory effects on certain populations of PVN neurons while it regulates other populations by acting through presynaptic glutamatergic interneurons