Serotonergic modulation of synapses in the developing gerbil lateral superior olive

Serotonergic modulation of synapses in the developing gerbil lateral superi or olive. J. Neurophysiol. 81: 2743-2752, 1999. The lateral superior olive (LSO) is a primary site of binaural convergence that responds selectively t o changes in interaural level difference (ILD) by integrating ipsilateral e xcitatory and contralateral inhibitory inputs. The circuit matures during t he first three postnatal weeks, undergoing several structural and functiona l 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-MT ) on LSO synaptic function. Using whole cell voltage-clamp recording from g erbil LSO neurons (postnatal days 6-13) in an in vitro slice preparation, w e have identified several distinct forms of serotonergic modulation of spon taneous and evoked synaptic transmission. First, 1-2 min application of 5-H T (100 mu M) activated prolonged bursts of spontaneous inhibitory postsynap tic currents (IPSCs). However, there was an age-dependent decline, such tha t this effect rarely was observed beyond postnatal day 8. 5-HT apparently i ncreased the excitability of inhibitory afferents, because 5-HT-induced IPS Cs were blocked by tetrodotoxin. A second effect of 5-HT was to depress rap idly and profoundly the amplitude of electrically evoked excitatory postsyn aptic currents (EPSCs). In contrast, 5-HT also depressed evoked IPSCs but t o a significantly lesser degree. The receptor subtypes mediating these effe cts were examined using specific 5-HT agonists and antagonists. A 5-MT, ago nist, 5-carbox-amidotryptamine, produced EPSC depression but did not induce spontaneous IPSCs. A 5-HT, agonist, alpha-Me-5-HT, reproduced all the obse rved effects of 5-HT (PSC depression as well as induction of spontaneous IP SCs), whereas a 5-HT, antagonist, ketanserin, blocked the induction of spon taneous IPSCs. Therefore induction of spontaneous IPSCs is mediated by 5-MT , receptors, whereas both 5-MT, and 5-MT, receptor types contribute to PSC depression. Serotonergic modulation of LSO synapses may have consequences f or both developmental plasticity and auditory function. Serotonergic induct ion of IPSCs was observed primarily in young animals and thus may represent a mechanism for amplifying the activity of inhibitory synapses in LSO duri ng a period of use-dependent plasticity in postnatal development. PSC depre ssion, which preferentially affects excitation, is a potential mechanism fo r modulation of ILD tuning.