The lateral superior olive (LSO) is a primary site of binaural convergence that responds selectively to changes in interaural level difference (ILD) by integrating ipsilateral excitatory and contralateral inhibitory inputs. The circuit matures during the first three postnatal weeks, undergoing several structural and functional changes that are influenced by afferent activity. Therefore modulation of synaptic activity by neuromodulators may participate in the maturation of this circuit. The present study describes robust effects of serotonin (5-HT) on LSO synaptic function. Using whole cell voltage-clamp recording from gerbil LSO neurons (postnatal days 6-13) in an in vitro slice preparation, we have identified several distinct forms of serotonergic modulation of spontaneous and evoked synaptic transmission. First, 1-2 min application of 5-HT (100 μM) activated prolonged bursts of spontaneous inhibitory postsynaptic currents (IPSCs). However, there was an age-dependent decline, such that this effect rarely was observed beyond postnatal day 8.5-HT apparently increased the excitability of inhibitory afferents, because 5-HT-induced IPSCs were blocked by tetrodotoxin. A second effect of 5-HT was to depress rapidly and profoundly the amplitude of electrically evoked excitatory postsynaptic currents (EPSCs). In contrast, 5-HT also depressed evoked IPSCs but to a significantly lesser degree. The receptor subtypes mediating these effects were examined using specific 5-HT agonists and antagonists. A 5-HT1 agonist, 5- carboxamidotryptamine, produced EPSC depression but did not induce spontaneous IPSCs. A 5-HT2 agonist, α-Me-5-HT, reproduced all the observed effects of 5-HT (PSC depression as well as induction of spontaneous IPSCs), whereas a 5-HT2 antagonist, ketanserin, blocked the induction of spontaneous IPSCs. Therefore induction of spontaneous IPSCs is mediated by 5-HT2 receptors, whereas both 5-HT1 and 5-HT2 receptor types contribute to PSC depression. Serotonergic modulation of LSO synapses may have consequences for both developmental plasticity and auditory function. Serotonergic induction of IPSCs was observed primarily in young animals and thus may represent a mechanism for amplifying the activity of inhibitory synapses in LSO during a period of use-dependent plasticity in postnatal development. PSC depression, which preferentially affects excitation, is a potential mechanism for modulation of ILD tuning.
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