Glutamate and GABA mediate suprachiasmatic nucleus inputs to spinal-projecting paraventricular neurons

Abstract

We used patch-clamp recordings in slice preparations from Sprague-Dawley rats to evaluate responses of 20 spinal-projecting neurons in the dorsal paraventricular nucleus (PVN) to electrical stimulation in suprachiasmatic nucleus (SCN). Neurons containing a retrograde label transported from the thoracic (T(1)-T(4)) intermediolateral column displayed three intrinsic properties that collectively allowed distinction from neighboring parvocellular or magnocellular cells: a low-input resistance, a hyperpolarization-activated time-dependent inward rectification, and a low-threshold calcium conductance. Twelve of fifteen cells tested responded to electrical stimulation in SCN. All of 10 cells tested in media containing 2,3,-dioxo-6-nitro-1,2,3,4-tetrahydrobenzo[f]quinoxaline-7-sulfonamide disodium (5 microM) and D(-)-2-amino-5-phosphonopentanoic acid (20 microM) responded with constant latency (11.4 +/- 0.7 ms) inhibitory postsynaptic potentials, able to follow 20- to 50-Hz stimulation and blockable with bicuculline (20 microM). By contrast, all eight cells tested in the presence of bicuculline demonstrated constant latency (9.8 +/- 0.6 ms) excitatory postsynaptic potentials that followed at 20-50 Hz and featured both non-N-methyl-D-aspartate (NMDA) and NMDA receptor-mediated components. We conclude that both GABAergic and glutamatergic neurons in SCN project directly to spinal-projecting neurons in the dorsal PVN.

Suprachiasmatic GABAergic Inputs to the Paraventricular Nucleus Control Plasma Glucose Concentrations in the Rat via Sympathetic Innervation of the Liver

“…The absence of a clear effect of VMH-TTX on plasma glucose concentrations substantiates the observation that GABAergic neurons are virtually absent from the VMH (Okamura et al, 1990) and that stimulation instead of inhibition of VMH neurons leads to hyperglycemia (Narita et al, 1994). GABAergic SCN inputs to the autonomic PVN neurons have been demonstrated in a number of electrophysiological experiments (Hermes et al, 1996;Cui et al, 2001;Wang et al, 2003). In addition, there is also evidence for GABAergic projections from the DMH to the PVN (Boudaba et al, 1996).…”

“…In addition to its neuroendocrine function, the PVN also has an important role in coordinating activity within the autonomic nervous system (ANS), as suggested by its connections with preganglionic parasympathetic and sympathetic centers (Saper et al, 1976). Several more-recent experiments have shown direct SCN input to these so-called autonomic PVN neurons (TeclemariamMesbah et al, 1997;Vrang et al, 1997;Cui et al, 2001). The critical role of the PVN in the control of feeding behavior and energy metabolism is well known.…”

Glutamatergic Inputs in the Hypothalamic Paraventricular Nucleus Maintain Sympathetic Vasomotor Tone in Hypertension

“…The excitability of PVN presympathetic neurons is finely regulated by both excitatory glutamatergic and inhibitory GABAergic inputs. 13,14,26 Conflicting results have been reported on the effect of microinjection of glutamate into the PVN on sympathetic vasomotor tone. For example, microinjection of glutamate into the PVN decreases or has no effect on arterial blood pressure and renal sympathetic activity in rats.…”

“…The glutamatergic synaptic input to the PVN presympathetic neurons originates mostly from interneurons within the PVN, the medial and lateral preoptic area, the suprachiasmatic nucleus, the anterior and lateral hypothalamus, the thalamic PVN, and some telencephalic regions (including the lateral septum, the bed nucleus of the stria terminalis, and the amygdala). 14,22,26 It should be noted that stimulation of the dorsomedial hypothalamus with bicuculline or NMDA can increase sympathetic vasomotor tone in normotensive rats. 40,41 Although our study is focused on the PVN, we do not exclude the possibility that increased glutamatergic input may occur in the dorsomedial hypothalamus or other brain nuclei in SHRs.…”

“…24,25 Furthermore, electrophysiological studies using the hypothalamic slice preparation have shown that glutamatergic stimulation can excite PVN neurons and that blockade of glutamatergic transmission reduces spontaneous and evoked postsynaptic activity. 14,16,26 Previous studies have shown that microinjection of the glutamate receptor antagonist alone into the PVN has little effect on the sympathetic output and arterial blood pressure in normotensive rats. 15,27 These data suggest that the glutamatergic input in the PVN is not critically involved in tonic control of sympathetic vasomotor tone in normotensive conditions.…”