Adrenalectomy Potentiates Noradrenergic Suppression of GABAergic Transmission in Parvocellular Neurosecretory Neurons of Hypothalamic Paraventricular Nucleus

Abstract

Adrenalectomy potentiates noradrenergic suppression of GABAergic transmission in parvocellular neurosecretory neurons of hypothalamic paraventricular nucleus. J Neurophysiol 99: 514 -523, 2008. First published November 21, 2007 doi:10.1152/jn.00568.2007. Glucocorticoids are known to regulate both the noradrenergic and GABAergic inputs to the paraventricular nucleus (PVN). However, little is known about the effects of glucocorticoids on the interaction of these two input systems. Here we examined the effects of bilateral adrenalectomy (ADX) on the noradrenergic modulation of GABAergic transmission in the type II PVN neurons labeled with a retrograde dye injected into the pituitary stalk. Noradrenaline either reduced or augmented the frequency of spontaneous inhibitory postsynaptic current (sIPSC) without changing the amplitude and decay time constant. These effects were blocked by ␣ 2A -and ␣ 1A/1L -adrenoceptor antagonists, respectively. ADX increased the proportion of the neurons showing the noradrenergic reduction and the extent of reduction in the IPSC frequency. The ADX-induced changes were reversed by supplementation of ADX rats with corticosterone (10-mg pellet). ADX also potentiated the noradrenergic reduction in the frequency of miniature IPSC and paired-pulse facilitation of evoked IPSC. BRL 44408 (3 M), a ␣ 2A -adrenoceptor antagonist, blocked the noradrenergic reduction in ADX rats. Corticotropin-releasing hormone and/or vasopressin transcripts were detected in neurons displaying noradrenergic augmentation or reduction of IPSC frequency. ADX enhanced the proportion of neurons expressing corticotropin-releasing hormone. Collectively, the results suggest that depletion of corticosterone by ADX markedly potentiates the noradrenergic suppression of GABAergic transmission mediated by the ␣ 2A -adrenoceptors on the GABAergic terminals in the parvocellular neurosecretory PVN neurons. These results may provide a novel synaptic mechanism for the glucocorticoid-induced plasticity in the noradrenergic modulation of neuroendocrine function of the PVN.

Synaptic regulation of the hypothalamic–pituitary–adrenal axis and its modulation by glucocorticoids and stress

“…In another 33% of the neurons tested, norepinephrine reduced the IPSC frequency, and this reduction was mediated by α 2 -adrenoceptors and was spike-independent, suggesting a presynaptic terminal locus of action (Han et al, 2002). In another study that specifically targeted parvocellular neuroendocrine cells with electrophysiological markers and retrograde staining from the median eminence, norepinephrine suppressed GABAergic input in 46% of the cells tested, and this was increased to 100% following blockade of either α 1 -adrenoceptors or spike generation (Yang et al, 2008). Consistent with α 2 -adrenoceptors located on GABAergic boutons inhibiting GABA release onto CRH cells, binding assays have reported substantial binding of radiolabeled clonidine, an α 2 -adrenoceptor agonist, in the CRH cell region of the medial parvocellular PVN (Cummings and Seybold, 1988).…”

“…Consistent with α 2 -adrenoceptors located on GABAergic boutons inhibiting GABA release onto CRH cells, binding assays have reported substantial binding of radiolabeled clonidine, an α 2 -adrenoceptor agonist, in the CRH cell region of the medial parvocellular PVN (Cummings and Seybold, 1988). Moreover, electrophysiological analyses indicate that the α 2 -adrenoceptor-mediated decrease in GABA input is reflective of a reduced probability of GABA release (Yang et al, 2008). In keeping with its suppressive effect on neurotransmitter release, the α 2 -adrenoceptor is commonly found to suppress norepinephrine release as an autoreceptor (Raiteri et al, 1992).…”

Direct Corticosteroid Modulation of GABAergic Neurons in the Anterior Hypothalamic Area of GAD65-eGFP Mice

“…Removal of endogenous corticosterone, by adrenalectomy (ADX), can affect GABAergic transmission in the PVN. For example, ADX altered the excitability of neurosecretory PVN neurons in rats [10] and increased GABAergic transmission in the PVN [11,12]. Stress in rats, or in vitro exposure of the brain slice to corticosterone suppressed GABAergic transmission [13], and altered the expression of GABAA receptor subunits [14].…”

Identifying Links in the Chain

“…We propose that this integrator includes catecholaminergic inputs. Although this network is electrophysiologically well defined [Bains & Ferguson, 1999; Boudaba et al, 1996; Chong et al, 2004; Daftrey et al, 2000; Han et al, 2002; Hewitt et al, 2009; Iremonger et al, 2010; Kuzmiski et al, 2010; Levy & Tasker, 2012; Marty et al, 2011; Verkuyl et al, 2005; Yang et al, 2008], anatomically it remains an enigma, particularly regarding the location of the GABA and glutamate pre-motor neurons. Some of these are located distally [Herman et al, 2003; Ulrich-Lai et al, 2011; Zeigler et al, 2012], but electrophysiological studies using PVH slices—where only elements close to the PVH remain functional—strongly support a more proximal location for others [Boudaba et al, 1996; Cullinan et al, 2008; Daftrey et al, 2000; Herman et al, 2002] including GABA or glutamate interneurons within or close to the PVH [Csáki et al, 2000; Daftrey et al, 2000; Roland et al, 1993].…”