Serotonergic Modulation of GABAergic and Glutamatergic Synaptic Transmission in Mechanically Isolated Rat Medial Preoptic Area Neurons

Abstract

The medial preoptic area (MPOA) of the hypothalamus is critically involved in the regulation of male sexual behavior and has been implicated in several homeostatic processes. Serotonin (5-hydroxytryptamine, 5-HT) inhibits sexual behavior via effects in the MPOA, where there are high densities of 5-HT 1A and 5-HT 1B receptor subtypes. We used whole-cell recordings under voltage-clamp conditions to investigate the serotonergic modulation of g-aminobutyric acid (GABA)ergic and glutamatergic synaptic transmission in mechanically dissociated rat MPOA neurons with native presynaptic nerve endings. Spontaneous GABAergic miniature inhibitory postsynaptic currents (mIPSCs) in the MPOA were completely blocked by bicuculline. Serotonin reversibly reduced the GABAergic mIPSC frequency without affecting the mean current amplitude. Serotonergic inhibition of mIPSC frequency was mimicked by (7)-8-hydroxy-2-dipropylaminotetralin hydrobromide, a specific 5-HT 1A receptor agonist, and blocked by 1-(2-methoxyphenyl)-4-[4-(2-phthalimido)-butyl] piperazine hydrobromide, a specific 5-HT 1A receptor antagonist. 6-Cyano-7-nitroquinoxaline-2,3-dione completely blocked spontaneous glutamatergic miniature excitatory postsynaptic currents (mEPSCs) in the MPOA. Serotonin reversibly decreased the glutamatergic mEPSC frequency without affecting the mean current amplitude. Serotonergic inhibition of mEPSC frequency was mimicked by CGS 12066B, a specific 5-HT 1B receptor agonist, and blocked by SB 216641, a specific 5-HT 1B receptor antagonist. Stimulation of adenylyl cyclase with forskolin increased the frequencies of GABAergic mIPSCs and glutamatergic mEPSCs, and blocked the inhibitory effects of 5-HT. H-89, a selective protein kinase A (PKA) inhibitor, decreased the frequencies of GABAergic mIPSCs and glutamatergic mEPSCs, and blocked their reduction by 5-HT. These findings suggest that 5-HT reduces the frequency of GABAergic mIPSCs and glutamatergic mEPSCs through 5-HT 1A and 5-HT 1B receptor-mediated inhibition, respectively, of the PKA-dependent pathway in the presynaptic nerve terminals of MPOA neurons.

Swim stress activates serotonergic and nonserotonergic neurons in specific subdivisions of the rat dorsal raphe nucleus in a temperature-dependent manner

“…There is evidence for both serotonergic and non-serotonergic projections from the DRI to the MPO (Tillet, 1992) and therefore DRI serotonergic neurons may also play a role in thermoregulation. Previous studies have characterized expression of 5-HT 1A (Marvin et al, 2010) and 5-HT 1B (Pazos and Palacios, 1985) receptors in the MPO, and have shown neuromodulatory effects of 5-HT on MPO neurons via 5-HT 1A and 5-HT 1B receptors (Lee et al, 2008). Superfusion of the 5-HT 1A selective agonist, 8-hydroxy-N,N-dipropyl-2-aminotetralin, decreases GABAergic miniature inhibitory postsynaptic current frequencies and superfusion of a 5-HT 1B selective agonist, 7-trifluoromethyl-4-(4-methyl-1-piperazinyl)pyrrolo[1,2-a]-quinoxaline dimaleate, decreases miniature excitatory postsynaptic current frequencies (Lee et al, 2008).…”

“…Previous studies have characterized expression of 5-HT 1A (Marvin et al, 2010) and 5-HT 1B (Pazos and Palacios, 1985) receptors in the MPO, and have shown neuromodulatory effects of 5-HT on MPO neurons via 5-HT 1A and 5-HT 1B receptors (Lee et al, 2008). Superfusion of the 5-HT 1A selective agonist, 8-hydroxy-N,N-dipropyl-2-aminotetralin, decreases GABAergic miniature inhibitory postsynaptic current frequencies and superfusion of a 5-HT 1B selective agonist, 7-trifluoromethyl-4-(4-methyl-1-piperazinyl)pyrrolo[1,2-a]-quinoxaline dimaleate, decreases miniature excitatory postsynaptic current frequencies (Lee et al, 2008). Previous findings have also shown functional responses to 5-HT in the MPO through intra-MPO injection of 5-HT resulting in either hypothermia (Ruwe and Myers, 1982; Lin et al, 1983) or hyperthermia (Datta et al, 1988; Huttunen et al, 1988).…”

A role of CB1R in inducing θ-rhythm coordination between the gustatory and gastrointestinal insula

“…However, it has also been reported that cannabinoids increased glutamatergic transmission by activation of the CB1R in cortical neurons34, in which CB1R activation may have downregulated cAMP production rather than inhibiting presynaptic Ca 2+ channels, because it is known that the upregulation of cAMP production decreases glutamate release in L5/6 PCs in the prefrontal cortex35. Conversely, it has been reported that downregulation of cAMP production by 5-HT 1A or adenosine A 1 receptors resulted in the inhibition of GABA release3637.…”

Modulation of Presynaptic GABA Release by Oxidative Stress in Mechanically-isolated Rat Cerebral Cortical Neurons

“…A recent report demonstrated that H2O2 increased GABAergic mIPSCs through presynaptic release of Ca 2＋ from inositol-1,4,5-trisphosphate receptor-sensitive Ca 2＋ stores in the spinal cord substantia gelatinosa neurons [22]. In addition, several reports have demonstrated that cAMP-dependent PKA has an important role in certain conditions showing an increase in presynaptic GABA release in many neuronal preparations [31][32][33]. However, it is not clear whether cAMP-dependent PKA is involved in the effect of H2O2 on presynaptic GABA release.…”