Abstract
Excitatory synaptic transmission in central synapses is modulated by serotonin (5-HT). The anterior cingulate cortex (ACC) is an important cortical region for pain perception and emotion. ACC neurons receive innervation of projecting serotonergic nerve terminals from raphe nuclei, but the possible effect of 5-HT on excitatory transmission in the ACC has not been investigated. In the present study, we investigated the role of 5-HT on glutamate neurotransmission in the ACC slices of adult mice. Bath application of 5-HT produced dose-dependent inhibition of evoked excitatory postsynaptic currents (eEPSCs). Paired pulse ratio (PPR) was significantly increased, indicating possible presynaptic effects of 5-HT. Consistently, bath application of 5-HT significantly decreased the frequency of spontaneous and miniature excitatory postsynaptic currents (sEPSCs and mEPSCs). By contrast, amplitudes of sEPSCs and mEPSCs were not significantly affected. After postsynaptic application of G protein inhibitor GDP-β-S, 5-HT produced inhibition of eEPSCs was significantly reduced. Finally, NAN-190, an antagonist of 5-HT1A receptor, significantly reduced postsynaptic inhibition of 5-HT and abolished presynaptic inhibition. Our results strongly suggest that presynaptic as well as postsynaptic 5-HT receptor including 5-HT1A subtype receptor may contribute to inhibitory modulation of glutamate release as well as postsynaptic responses in the ACC.
Highlights
As one important neurotransmitter in the central nervous system (CNS), serotonin (5-hydroxytryptamine, 5-HT) plays a crucial role in numerous physiological functions
In the presence of the GABAA receptor antagonist, picrotoxin (100 μM), EPSCs evoked by a single-pulse stimulation were recorded with the membrane potential holding at −60 mV and the baseline amplitude of evoked excitatory postsynaptic currents (eEPSCs) was adjusted at 50–100 pA
Washing out of 5-HT with control artificial cerebrospinal fluid (ACSF), it partially reversed the reduction of eEPSC amplitude caused by 5-HT (5 μM: 80.5 ± 7.4% of baseline, n = 9/6, p < 0.05 compared with the 5-HT, Fig. 1d and e; 50 μM: 66.1 ± 6.3% of baseline, n = 6/4, data not shown)
Summary
As one important neurotransmitter in the central nervous system (CNS), serotonin (5-hydroxytryptamine, 5-HT) plays a crucial role in numerous physiological functions. It has been implicated in pain modulation [1] and emotional disorders [2]. The ACC is a critical cortical region, which plays a central role in the formation of pain perception and the unpleasantness of pain [1, 9, 10]. Neurons of the ACC receive sensory inputs projecting from other subcortical areas (such as the thalamus) and project to related sensory regions, including amygdala, midbrain areas, brainstem and spinal cord [11, 12]. Injuries enhanced synaptic transmission in the ACC and inhibition of the ACC potentiation is analgesic in animal models of
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