Presynaptic α-adrenoceptors in median preoptic nucleus modulate inhibitory neurotransmission from subfornical organ and organum vasculosum lamina terminalis

Abstract

The median preoptic nucleus (MnPO) in the lamina terminalis receives a prominent catecholaminergic innervation from the dorsomedial and ventrolateral medulla. The present investigation used whole cell patch-clamp recordings in rat brain slice preparations to evaluate the hypothesis that presynaptic adrenoceptors could modulate GABAergic inputs to MnPO neurons. Bath applications of norepinephrine (NE; 20-50 microM) induced a prolonged and reversible suppression of inhibitory postsynaptic currents (IPSCs) and reduced paired-pulse depression evoked by stimulation in the subfornical organ and organum vasculosum lamina terminalis. These events were not correlated with any observed changes in membrane conductance arising from NE activity at postsynaptic alpha(1)- or alpha(2)-adrenoceptors. Consistent with a role for presynaptic alpha(2)-adrenoceptors, responses were selectively mimicked by an alpha(2)-adrenoceptor agonist (UK-14304) and blockable with an alpha(2)-adrenoceptor antagonist (idazoxan). Although the alpha(1)-adrenoceptor agonist cirazoline and the alpha(1)-adrenoceptor antagonist prazosin were without effect on these evoked IPSCs, NE was noted to increase (via alpha(1)-adrenoceptors) or decrease (via alpha(2)-adrenoceptors) the frequency of spontaneous and tetrodotoxin-resistant miniature IPSCs. Collectively, these observations imply that both presynaptic and postsynaptic alpha(1)- and alpha(2)-adrenoceptors in MnPO are capable of selective modulation of rapid GABA(A) receptor-mediated inhibitory synaptic transmission along the lamina terminalis and therefore likely to exert a prominent influence in regulating cell excitability within the MnPO.

The effects of Cirazoline, an alpha-1 adrenoreceptor agonist, on the firing rates of thermally classified anterior hypothalamic neurons in rat brain slices

“…This early hyperthermia likely attenuates due to eventual desensitization at the postsynaptic alpha-1 ARs, the induction of COX-2 expression by activation of alpha-2 ARs, ensuing PGE 2 synthesis, and action at Prostaglandin E receptors (EP; presumably the EP 3 subtype) which contribute the late phase of fever (Feleder et al, 2007;Lazarus et al, 2007;Oka, 2004). The application of norepinephrine in the POAH has been shown to increase the frequency of spontaneous, miniature inhibitory postsynaptic currents (IPSCs) via the alpha-1 AR, and likewise decrease the frequency of IPSCs via the alpha-2 AR (Kolaj and Renaud, 2007). These observations indicate that these two ARs can modify rapid GABA-mediated inhibitory transmission and thus have a central role in regulating excitability within this noradrenergic network of thermoregulatory neurons.…”

Metabotropic Glutamate Receptors in Median Preoptic Neurons Modulate Neuronal Excitability and Glutamatergic and GABAergic Inputs From the Subfornical Organ

“…In previous investigations, we noted that electrical stimulation in the SFO or along its ventral border could elicit glutamate-mediated EPSCs or GABA A receptor-mediated IPSCs in MnPO neurons (Kolaj and Renaud 2007;Kolaj et al 2004Kolaj et al , 2007. Similar protocols were used here to evaluate the hypothesis that mGluRs might attenuate SFO-evoked inputs.…”

“…At the midpoint of the lamina terminalis and surrounding the anterior commissure is the median preoptic nucleus (MnPO, also called nucleus medianus, MnPN or POMe) containing neurons that receive inputs and interconnect with those in the SFO and OVLT as noted in both anatomical (e.g., Miselis et al 1979;Oldfield et al 1992) and functional studies (e.g., Gutman et al 1989;Kolaj and Renaud 2007;Kolaj et al 2004;Tanaka et al 1987). MnPO neurons are suitably positioned to acquire information that derives from both hemal and neural origins.…”

Changes in vasopressin release and autonomic function induced by manipulating forebrain GABAergic signaling under euvolemia and hypovolemia in conscious rats

“…A part of A1 neurons may project to the AVP cells directly without going through the AV3V [5]. The NAergic signals potentiated by the hypovolemia may act to inhibit GABAergic activity in the AV3V and SFO [22,51]. GABAergic neurons, as well as glutamatergic neurons, are shown to project from the SFO or OVLT to the MnPO [20].…”

“…The star-shaped objects at the right side represent the AVP cells. As stated above, bleeding-evoked Hvs conveyed from the brainstem areas could inactivate asterisked GABAergic neurons [51] to cause resultant potentiation in glutamatergic (Glu) influence on excitatory pathways (Ex) in the models [A] and [B] or on GABAergic neurons innervating inhibitory pathway (In) to the AVP cells in the model [C]. Infusion of the GABAergic antagonist bicuculline may also block function of the asterisked neurons to exert similar potency.…”