GABAB Receptor Modulation of Rapid Inhibitory and Excitatory Neurotransmission From Subfornical Organ and Other Afferents to Median Preoptic Nucleus Neurons

2004 ◽  
Vol 92 (1) ◽  
pp. 111-122 ◽  
Author(s):  
Miloslav Kolaj ◽  
Donglin Bai ◽  
Leo P. Renaud
Keyword(s):  
Gabab Receptor ◽  
Potassium Conductance ◽  
Subfornical Organ ◽  
Receptor Subtypes ◽  
Preoptic Nucleus ◽  
Paired Pulse ◽  
Median Preoptic Nucleus ◽  
Postsynaptic Currents ◽  
Receptor Modulation ◽  
Rat Brain Slice

Cardiovascular and behavioral responses to circulating angiotensin require intact connectivity along the upper lamina terminalis joining the subfornical organ (SFO) with the median preoptic nucleus (MnPO). Whole cell patch-clamp recordings in sagittal rat brain slice preparations revealed that 28/40 MnPO neurons responded to electrical stimulation of SFO efferents with bicuculline-sensitive GABAA receptor-mediated inhibition and glutamate-mediated postsynaptic excitation involving AMPA and N-methyl-d-aspartate (NMDA) receptor subtypes, blockable with 2,3-dioxo-6nitro-1, 2,3,4-tetrahydrobenzo [f] quinoxaline-7-sulfoamide disodium (NBQX) and d-2-amino-4-phosphonovaleric acid (d-APV), respectively. Bath applications of baclofen induced a concentration-dependent (0.3–10 μM) reduction in these SFO-evoked postsynaptic currents, attenuation of SFO-evoked paired-pulse depression, and reduction in frequency (but not amplitude) of miniature postsynaptic currents, consistent with an action at presynaptic GABAB receptors. Baclofen's effects on miniature currents lacked sensitivity to barium, ω-conotoxin GVIA, and cadmium. Acting at postsynaptic GABAB receptors, baclofen hyperpolarized a majority of MnPO neurons by increasing a G protein–coupled inwardly rectifying potassium conductance and suppressing an N-type high-voltage–activated calcium conductance. The latter contributed to reduction in action potential afterhyperpolarization and enhanced cell firing and spike frequency adaptation when tested with a depolarizing stimulus. All baclofen-induced effects were blockable with CGP52432 . CGP52432 alone had no significant effect on SFO-evoked postsynaptic current amplitudes or paired-pulse ratios, but did induce an increase in miniature inhibitory postsynaptic current (mIPSC) frequency in 2/4 cells tested, indicating that ambient levels of GABA could activate presynaptic GABAB receptors on undefined inputs. These observations indicate that MnPO neurons receive both a GABAergic and glutamatergic innervation from SFO. Both forms of rapid neurotransmission are subject to modulation via pre- and postsynaptic GABAB receptors.

Multiple receptor subtypes mediate the effects of serotonin on rat subfornical organ neurons

1998 ◽  
Vol 275 (6) ◽  
pp. R2035-R2042 ◽  
Author(s):  
Karie E. Scrogin ◽  
Alan Kim Johnson ◽  
Herbert A. Schmid
Keyword(s):  
Receptor Agonist ◽  
Brain Slice ◽  
Subfornical Organ ◽  
Receptor Subtypes ◽  
Ang Ii ◽  
Excitatory Responses ◽  
Rat Brain Slice ◽  
Dose Dependent ◽  
Multiple Receptor ◽  
Serotonergic Innervation

The subfornical organ (SFO) receives significant serotonergic innervation. However, few reports have examined the functional effects of serotonin on SFO neurons. This study characterized the effects of serotonin on spontaneously firing SFO neurons in the rat brain slice. Of 31 neurons tested, 80% responded to serotonin (1–100 μM) with either an increase ( n = 15) or decrease ( n = 10) in spontaneous activity. Responses to serotonin were dose dependent and persisted after synaptic blockade. Excitatory responses could also be mimicked by the 5-hydroxytryptamine (5-HT)2A/2C receptor agonist 2,5-dimethoxy-4-iodoamphetamine (DOI; 1–10 μM) and could be blocked by the 5-HT2A/2C-receptor antagonist LY-53,857 (10 μM). LY-53,857 unmasked inhibitory responses to serotonin in 56% of serotonin-excited cells tested. Serotonin-inhibited cells were also inhibited by the 5-HT1A-receptor agonist 8-hydroxy-2(di- n-propylamino)tetralin (8-OH-DPAT; 1–10 μM; n = 7). The data indicate that SFO neurons are responsive to serotonin via postsynaptic activation of multiple receptor subtypes. The results suggest that excitatory responses to serotonin are mediated by 5-HT2A or 5-HT2C receptors and that inhibitory responses may be mediated by 5-HT1A receptors. In addition, similar percentages of serotonin-excited and -inhibited cells were also sensitive to ANG II. As such the functional relationship between serotonin and ANG II in the SFO remains unclear.

Functional identification of central pressor pathways originating in the subfornical organ

1991 ◽  
Vol 69 (7) ◽  
pp. 1035-1045 ◽  
Author(s):  
John Ciriello ◽  
Michael B. Gutman
Keyword(s):  
Spinal Cord ◽  
Electrical Stimulation ◽  
Paraventricular Nucleus ◽  
Supraoptic Nucleus ◽  
Subfornical Organ ◽  
Preoptic Nucleus ◽  
Thoracic Spinal Cord ◽  
Median Preoptic Nucleus ◽  
Pressor Responses ◽  
Stimulation Of

The functional projections from pressor sites in the subfornical organ (SFO) were identified using the 2-deoxyglucose (2-DG) autoradiographic method in urethane-anesthetized, sinoaortic-denervated rats. Autoradiographs of brain and spinal cord sections taken from rats whose SFO was continuously stimulated electrically for 45 min with stereotaxically placed monopolar electrodes (150 μA, 1.5-ms pulse duration, 15 Hz) following injection of tritiated 2-DG were compared with control rats that received intravenous infusions of pressor doses of phenylephrine to mimic the increase in arterial pressure observed during SFO stimulation. Comparisons were also made to autoradiographs from rats in which the ventral fornical commissure (CFV), just dorsal to the SFO, was electrically stimulated. The pressor responses during either electrical stimulation of the SFO or intravenous infusion of phenylephrine were similar in magnitude. On the other hand, stimulation of the CFV did not elicit a significant pressor response. Electrical stimulation of the SFO increased 2-DG uptake, in comparison to the phenylephrine-infused rats, in the nucleus triangularis, septofimbrial nucleus, lateral septal nucleus, nucleus accumbens, bed nucleus of the stria terminalis, dorsal and ventral nucleus medianus (median preoptic nucleus), paraventricular nucleus of the thalamus, hippocampus, supraoptic nucleus, suprachiasmatic nucleus, paraventricular nucleus of the hypothalamus, and the intermediolateral nucleus of and central autonomic area of the thoracic spinal cord. In contrast, in rats whose CFV was stimulated, these nuclei did not demonstrate changes in 2-DG uptake compared with control animals that received pressor doses of phenylephrine. These data have demonstrated some of the components of the neural circuitry likely involved in mediating the pressor responses to stimulation of the SFO and the corrective responses to activation of the SFO by disturbances to circulatory and fluid balance homeostasis.Key words: cardiovascular reflex pathways, drinking, median preoptic nucleus, osmoreceptors, paraventricular nucleus of the hypothalamus, supraoptic nucleus.

Subfornical organ disconnection alters Fos expression in the lamina terminalis, supraoptic nucleus, and area postrema after intragastric hypertonic NaCl

2005 ◽  
Vol 288 (4) ◽  
pp. R947-R955 ◽  
Author(s):  
Julia A. Freece ◽  
Julie E. Van Bebber ◽  
Dannielle K. Zierath ◽  
Douglas A. Fitts
Keyword(s):  
Supraoptic Nucleus ◽  
Area Postrema ◽  
Anterior Commissure ◽  
Subfornical Organ ◽  
Main Body ◽  
Lamina Terminalis ◽  
Preoptic Nucleus ◽  
Median Preoptic Nucleus ◽  
Organum Vasculosum Laminae Terminalis ◽  
Initial Load

The lamina terminalis was severed by a horizontal knife cut through the anterior commissure to determine the effects of a disconnection of the subfornical organ (SFO) on drinking and Fos-like immunoreactivity (Fos-ir) in the rat brain in response to an intragastric load of hypertonic saline (5 ml/kg of 1.5 M NaCl by gavage). After an initial load, knife-cut rats drank significantly less water than sham-cut rats, thus confirming a role for the SFO in osmotic drinking. After a second load at least 1 wk later, the rats were not allowed to drink after the gavage and were perfused for analysis of Fos-ir at 90 min. Compared with sham-cut rats, the knife-cut rats displayed significantly elevated Fos-ir in the main body of the SFO, in the dorsal cap of the organum vasculosum laminae terminalis, and in the ventral median preoptic nucleus after the hypertonic load. The knife cut significantly decreased Fos-ir in the supraoptic nucleus. Fos-ir was expressed mainly in the midcoronal and caudal parts of the area postrema of sham-cut rats, and this expression was greatly reduced in knife-cut rats. These findings strengthen the case for the presence of independently functioning osmoreceptors within the SFO and suggest that the structures of the lamina terminalis provide mutual inhibition during hypernatremia. They also demonstrate that the Fos-ir in the area postrema after intragastric osmotic loading is heavily dependent on the intact connectivity of the SFO.

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

2010 ◽  
Vol 103 (2) ◽  
pp. 1104-1113 ◽  
Author(s):  
Miloslav Kolaj ◽  
Leo P. Renaud
Keyword(s):  
Metabotropic Glutamate Receptors ◽  
Metabotropic Glutamate Receptor ◽  
Subfornical Organ ◽  
Lamina Terminalis ◽  
Patch Clamp Recording ◽  
Paired Pulse ◽  
Metabotropic Glutamate ◽  
Postsynaptic Currents ◽  
Group I ◽  
Group Ii

Cardiovascular and behavioral responses to circulating angiotensin require intact connectivity along the upper lamina terminalis joining the subfornical organ (SFO) with the median preoptic nucleus (MnPO). In the present study on MnPO neurons, we used whole cell patch-clamp recording techniques in brain slice preparations to evaluate the influence of metabotropic glutamate receptor (mGluR) agonists on modulating their intrinsic excitability and SFO-evoked glutamatergic and GABAergic postsynaptic currents. In 22/36 cells, bath application of a mGluR group I agonist ( S)-3,5-dihydroxyphenylglycine (DHPG) induced a TTX-resistant inward current coupled with decrease in a membrane K+ conductance but also a possible increase in a nonselective cationic conductance. By contrast, 27/49 cells responded to a mGluR group II agonist (2S,2′R,3′R)-2-(2′,3′-dicarboxycyclopropyl)glycine (DCG IV) with a TTX-resistant outward current and increase in membrane conductance that reversed around −95 mV, suggesting opening of K+ channels. None of 19 cells responded to the mGluR group III agonist l-(+)-2-amino-4-phosphonobutyric acid (l-AP4). Agonists for all mGluR groups suppressed SFO-evoked excitatory postsynaptic currents and significantly increased paired-pulse ratios, implying a presynaptic mechanism. Only the mGluR group II agonist significantly reduced SFO-evoked inhibitory postsynaptic currents and caused an increase in paired-pulse ratios. These results suggest a complexity of pre- and postsynaptic mGluRs are available to modulate rapid neurotransmission along the upper lamina terminalis from SFO to MnPO.

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