Inhibition by 5-HT of the synaptic responses evoked by callosal fibers on cortical neurons in the mouse
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We have studied the modulation by 5-HT of the synaptic excitatory responses evoked by callosal fibers on cortical pyramidal neurons. We have used a mouse brain slice preparation that preserves the callosal fibers and allows their selective activation. EPSCs evoked by callosal stimulation (ccEPSCs) were recorded with patch electrodes from pyramidal neurons identified visually. We observed that 5-HT (10–40 μM) inhibited the ccEPSCs peak amplitude in 64% of the neurons; 5-HT had no effect in the remaining neurons. 5-HT also increased the frequency and amplitude of spontaneous EPSCs. This inhibition was accompanied with an increase in the coefficient of variation of the fluctuations of the ccEPSCs amplitude and with an increase in the ratio of the amplitudes of paired ccEPSCs. Agonists of 5-HT receptor subtypes 5-HT1A (8-OH-DPAT) and 5-HT2A (DOI) mimicked the effect of 5-HT; also, the effect of 8-OH-DPAT and DOI was blocked in the presence of specific blockers of 5-HT1A (WAY 100135) and 5-HT2A (MDL 11,939) receptors. Application of 5-HT did not change the amplitude of currents evoked by direct application of glutamate to neurons in which 5-HT decreased the amplitude of ccEPSC. The effects of 5-HT on ccEPSCs and on the synaptic currents evoked by intracortical stimulation were not correlated; this suggests that the effect of 5-HT was specific to particular synaptic inputs to a neuron. These results demonstrate the presynaptic modulation of the callosal synaptic responses by 5-HT and the implication of 5-HT1A and 5-HT2A receptors in this effect.
KeywordsBrain slices Serotonin Cerebral cortex 5-Hydroxytryptamine receptor Synaptic transmission
Artificial cerebrospinal fluid
Synaptic currents evoked by callosal stimulation
((2S)-3-[[(1S)-1-(3,4-Dichlorophenyl) ethyl]amino-2-hydro xypropyl](phenylmethyl)phosphinic acid hydrochloride)
Coefficient of variation
- DAB, 3
Synaptic responses evoked by intracortical stimulation
- MDL 11,939
- WAY 100135
We are grateful to Dr. L. Almaraz for helpful comments on the manuscript, to Dr. P. Berbel for the help on the use of the Neurograph software and on drawing neurons, and to Mr. A. Pérez-Vegara for the technical assistance. This study was supported by grants AP 090/08 and PROMETEO (Generalitat Valenciana), grant PI052561 (Instituto de Salud Carlos III), grant from the Fundación Navarro-Trípodi, and Grupo Consolider (Spanish Ministry of Education and Science Grant CONSOLIDER-INGENIO 2010 CSD2007-00023).
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