Glutamatergic Inputs Contribute to Phasic Activity in Vasopressin Neurons

Abstract

Many neurons in the CNS display rhythmic patterns of activity to optimize excitation-secretion coupling. However, the mechanisms of rhythmogenesis are only partially understood. Magnocellular vasopressin (VP) neurons in the hypothalamus display a phasic activity that consists of alternative bursts of action potentials and silent periods. Previous observations from acute slices of adult hypothalamus suggested that VP cell rhythmicity depends on intrinsic membrane properties. However, such activity in vivo is nonregenerative. Here, we studied the mechanisms of VP neuron rhythmicity in organotypic slice cultures that, unlike acute slices, preserve functional synaptic connections. Comparative analysis of phasic firing of VP neurons in vivo, in acute slices, and in the cultures revealed that, in the latter, the activity was closely related to that observed in vivo. It was synaptically driven, essentially from glutamatergic inputs, and did not rely on intrinsic membrane properties. The glutamatergic synaptic activity was sensitive to osmotic challenges and -opioid receptor activation, physiological stimuli known to affect phasic activity. Together, our data thus strongly suggest that phasic activity in magnocellular VP neurons is controlled by glutamatergic synaptic inputs rather than by intrinsic properties.

Neonatal testosterone suppresses a neuroendocrine pulse generator required for reproduction

“…This sustained activity, either in bursts of APs for OT neurons or phasic for VP neurons, is known in vivo to specifically allow the release of boluses of neurohormone into the blood stream 14 . The electrical activities of OT and VP neurons are quite similar in organotypic cultures and in vivo 17,28 , and the ability of OT neurons to burst in vitro fully recapitulates the known programme of sexual differentiation of the hypothalamus 15 . Thus, we likely provide here evidence for the existence of two separate neuroendocrine pattern (or pulse) generators 7 .…”

“…Neurons that did not display spontaneous bursting activity after 15-20 min of recording were subjected to three phenotyping challenges. Either exogenous OT or bicuculline was applied to trigger bursts or oscillatory activity, respectively; if these approaches were inefficient, a hyperosmotic test ( þ 25 mOsm) was administered to reveal phasic activity typical of vasopressinergic neurons 17 . On rare occasions these tests were negative, and triple-labelling immunocytochemistry was performed to reveal biocytin, OT and VP.…”

“…In contrast, cognate magnocellular vasopressin (VP) neurons typically had an unsynchronized activity ( Supplementary Fig. 1b,c) like in vivo 14 and their phasic activity depended on a glutamatergic 17 CPG that was essentially unresponsive to bicuculline (Fig. 1h).…”

Kainate Receptor-Induced Retrograde Inhibition of Glutamatergic Transmission in Vasopressin Neurons

“…This process could thus serve to reduce the impact of excitatory inputs on VP neuron firing, enabling these cells to develop a more autonomous activity. This could be important for the rhythmic phasic activity displayed by VP neurons in response to physiological stimulation, such as dehydration or hemorrhage, which is believed to depend on both intrinsic membrane properties and extrinsic synaptic influence (Israel et al, 2010).…”

Ultrastructural characterization of tumor necrosis factor alpha receptor type 1 distribution in the hypothalamic paraventricular nucleus of the mouse

“…In the present study, TNFR1 immunoreactivity was identified in dendritic profiles receiving excitatory-type synapses characteristic of glutamate inputs (Peters et al, 1991). Glutamate activity in the PVN plays a critical role in homeostasis by influencing behavioral (Hettes et al, 2003), metabolic (Amir, 1990, Kalsbeek et al, 2008), neuroendocrine (Hattori et al, 1992, Feldman and Weidenfeld, 1997, Israel et al, 2010), and autonomic (Yeh et al, 1997, Zhang and Fogel, 2002, Crestani et al, 2010) processes. In particular, glutamate signaling in the PVN is an established central coordinator of sympathetic outflow critically involved in cardiovascular regulation (Ferguson et al, 2008, Kc and Dick, 2010).…”