Electrophysiology of 5-HT1A receptors in the rat hippocampus and cortex (original) (raw)
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Neuropharmacology, 2020
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Molecular Pharmacology, 2007
The entorhinal cortex (EC) is regarded as the gateway to the hippocampus; the superficial layers (layer I-III) of the EC convey the cortical input projections to the hippocampus, whereas deep layers of the EC relay hippocampal output projections back to the superficial layers of the EC or to other cortical regions. The superficial layers of the EC receive strong serotonergic projections from the raphe nuclei. However, the function of serotonin in the EC is still elusive. In the present study, we examined the molecular and cellular mechanisms underlying serotonin-mediated inhibition of the neuronal excitability in the superficial layers (layer II-III) of the EC. Application of serotonin inhibited the excitability of stellate and pyramidal neurons in the superficial layers of the EC by activating the TWIK-1 type of the two-pore domain K + channels. The effects of 5-HT were mediated via 5-HT 1A receptors and required the function of Gαi3 subunit and protein kinase A. Serotonin-mediated inhibition of EC activity resulted in an inhibition of hippocampal function. Our study provides a cellular mechanism that might at least partially explain the roles of serotonin in many physiological functions and neurological diseases.
British Journal of Pharmacology, 1993
1 The biophysical and pharmacological properties of 5-hydroxytryptamine (5-HT)-evoked currents in rabbit nodose ganglion neurones in culture have been determined by use of the whole-cell and outside-out membrane patch recording modes of the patch-clamp technique. 2 In 49% of cells investigated the bath application of 10-5 M 5-HT at negative holding potentials elicited an inward current. The whole-cell response to 5-HT reversed in sign (E5-HT) at approximately -2 mV and exhibited inward rectification.
Physiological effects of selective 5-HT1a and 5-HT1b ligands in rat hippocampus: comparison to 5-HT
Brain Research, 1989
The responses of CA1 neurons to topical application of serotonin (5-HT) and selective 5-HT~a and 5-HTlb agonists were examined with intracellular recording in the hippocampal slice. 5-HT produced a uniform hyperpolarizing response associated with an increase in K conductance as previously reported. In addition a marked reduction was recorded in slow afterhyperpolarization (AHP) which follows a burst discharge. 8-OH-DPAT, ipsapirone and LY165,163 partially mimicked the hyperpolarizing response to 5-HT when first applied to the slice. However, these 5-HTla ligands antagonized responses to subsequent applications of 5-HT. Topical application of the 5-HTtb ligand TFMPP on the slice did not produce the direct or antagonistic action seen with the 5-HT~a ligands. It is suggested that the physiological response to 5-HT in the rat hippocampus is mediated by a 5-HT~a receptor. The currently available 5-HT~a ligands show a low agonist potential and a high antagonist action towards the responses of hippocampal neurons to 5-HT. Definite classification of the hyperpolarizing response to 5-HT awaits development of more specific ligands having a pure agonistic activity.
Synapse, 1991
As a prerequisite to pharmacological analysis of the excitatory effects of serotonin (5-HT) on piriform pyramidal cells and interneurons, this study first examined the physiological characteristics of these two cell types. Intracellular recordings confirmed that the subpopulation of 5-HT-activated cells located at the border of layers II and III are indeed interneurons. Voltage clamp recordings in pyramidal cells showed that the increase in excitability produced by 5-HT in these cells was the result of voltage- and Ca(2+)-dependent outward currents with the characteristics of IM and IAHP. Pharmacological studies were designed to discriminate 5-HT2 from 5-HT1C responses in interneurons and pyramidal cells of piriform cortex. The 5-HT antagonist spiperone, which has a much higher affinity for 5-HT2 receptors than for 5-HT1C receptors, blocked the excitatory effect of 5-HT at lower concentrations in interneurons (IC50 = 31 nM) than in pyramidal cells (IC50 = 2.1 microM). Similarly, ritanserin, a drug which also has a higher affinity for 5-HT2 than 5-HT1C receptors, blocked the effect of 5-HT at lower concentrations in interneurons (IC50 = 400 nM) than in pyramidal cells (IC50 = 8.1 microM). In contrast, LY 53857, an antagonist with higher affinity for 5-HT1C than for 5-HT2 receptors, blocked the effect of 5-HT at lower concentrations in pyramidal cells (IC50 = 26 nM) than in interneurons (IC50 = 364 nM). The 5-HT1C partial agonist/5-HT2 antagonist mCPP produced agonist-like effects in only 66% of pyramidal cells tested indicating that not all pyramidal cells may express 5-HT1C receptors. In that both spiperone and ritanserin have higher affinity for 5-HT2 receptors than for 5-HT1C receptors and LY 53857 has a higher affinity for 5-HT1C receptors than for 5-HT2 receptors, these data suggest that in piriform cortex excitatory effects of 5-HT are mediated by 5-HT1C receptors in pyramidal cells an by 5-HT2 receptors in interneurons.
Brain Research, 1988
In vitro intracellular recording techniques in the rat brain slice preparation demonstrate that both serotonin (5-HT) and baclofen (a GABAB-receptor agonist) inhibit 5-HT neurons in the dorsal raphe nucleus by inducing a hyperpolarization of membrane potential and a decrease in apparent input resistance (Rin). Similar to previous results with 5-HT, baclofen-mediated inhibition of 5-HT neurons also shows an apparent reversal potential (Erev) of approximately-90 mV, consistent with mediation by K channels. In slices from rats that had previously received a local injection of pertussis toxin (0.5/~g) immediately rostral to the dorsal raphe nucleus, there was a virtually complete blockade of inhibition induced by both the serotonin autoreceptor and the GABAB-receptor. Intracellular injection of the stable GTP analog (guanosine-5'-O-(3-thiotriphosphate); GTPTS) mimicked the actions of both 5-HT and baclofen. The inhibitory actions of GTPTS were not additive with those of either 5-HT or baclofen, suggesting they share some common effector system. The stable cAMP analog (8-bromo-adenosine-3',5'-cyclic monophosphate (8-Br-cAMP)) had no effect on membrane potential or apparent input resistance and did not block the inhibitory actions mediated by 5-HT or baclofen. The local injection of pertussis toxin (0.5 /~g) caused a far greater blockade of 5-HT and baclofen-mediated inhibition than the intracerebroventricular (i.c.v.) injection of pertussis toxin (1.0~g). In parallel sets of animals with i.c.v, and local injections, we measured the pertussis toxin-mediated ADP-ribosylation of G proteins in membranes prepared from dorsal raphe nucleus. These biochemical studies showed that sensitivities to 5-HT and baclofen correlated with the concentration of remaining non-ADP-ribosylated G proteins following in vivo pertussis toxin injection. In summary, these results provide evidence for the role of a G protein(s) in the mediation of the cAMP-independent increase in potassium conductance in 5-HT neurons of dorsal raphe nucleus induced by both 5-HT1A-and GABAB-receptors.
Tandospirone-induced K+current in acutely dissociated rat dorsal raphe neurones
British Journal of Pharmacology, 1998
The eects of tandospirone (TDS) on dissociated rat dorsal raphe neurones were investigated using the patch-clamp method. 2 Under current-clamp conditions, TDS hyperpolarized the cell membrane, resulting in the reduction of ®ring rates. 3 Under voltage-clamp conditions, TDS induced an inward rectifying K + current in a concentrationdependent manner. 4 The TDS-induced K + currents (I TDS) were mimicked by 8-OH-DPAT, a 5-HT 1A agonist. The I TDS was blocked by spiperone, a 5-HT 1A receptor antagonist, in a concentration-dependent manner. 5 N-Ethylmaleimide, an agent which uncouples between the receptor and the G-protein, irreversibly blocked the I TDS. 6 In neurones perfused intracellularly with a pipette-solution containing GTP using the conventional whole-cell patch recording, the I TDS showed a gradual rundown. When the neurones were perfused with GTPgS, TDS activated the inwardly rectifying K + current in an irreversible manner. 7 In the inside-out patch recording mode, TDS-activated single K + channel currents (i TDS) which also showed an inward recti®cation. When the GDP in cytosolic side was completely replaced with GTP, the open probability of i TDS signi®cantly increased. 8 These results indicate that the activation of 5-HT 1A receptors by TDS directly opens the inward rectifying K + channels via a G-protein mediated process.
Molecular and Cellular Neuroscience, 2008
Whereas the entorhinal cortex (EC) receives profuse serotonergic innervations from the raphe nuclei in the brain stem and is critically involved in the generation of temporal lobe epilepsy, the function of serotonin (5-hydroxytryptamine, 5-HT) in the EC and particularly its roles in temporal lobe epilepsy are still elusive. Here we explored the cellular and molecular mechanisms underlying 5-HTmediated facilitation of GABAergic transmission and depression of epileptic activity in the superficial layers of the EC. Application of 5-HT increased sIPSC frequency and amplitude recorded from the principal neurons in the EC with no effects on mIPSCs recorded in the presence of TTX. However, 5-HT reduced the amplitude of IPSCs evoked by extracellular field stimulation and in synaptically connected interneuron and pyramidal neuron pairs. Application of 5-HT generated membrane depolarization, increased action potential firing frequency but reduced the amplitude of action potentials in presynaptic interneurons suggesting that 5-HT still increases GABA release whereas the depressant effects of 5-HT on evoked IPSCs could be explained by 5-HT-induced reduction in action potential amplitude. The depolarizing effect of 5-HT was mediated by inhibition of TASK-3 K + channels in interneurons and required the functions of 5-HT 2A receptors and Gα q/11 but was independent of phospholipase C activity. Application of 5-HT inhibited low-Mg 2+induced seizure activity in slices via 5-HT 1A and 5-HT 2A receptors suggesting that 5-HT-mediated depression of neuronal excitability and increase in GABA release contribute to its antiepileptic effects in the EC.