Inhibitory control at a synaptic relay

Abstract

The mammalian medial nucleus of the trapezoid body (MNTB) harbors one of the most powerful terminals in the CNS, the calyx of Held. The mechanisms known to regulate this synaptic relay are relatively ineffective. Here, we report the presence of a remarkably robust and fast-acting glycinergic inhibitory system capable of suppressing calyceal transmission. Evoked glycinergic IPSCs were relatively small in 2-week-old rats, an age by which calyceal maturation has reportedly neared completion. However, by postnatal day 25 (P25), glycinergic transmission had undergone a vigorous transformation, resulting in peak synaptic conductances as high as 280 nS. These are comparable with glutamatergic conductances activated by calyceal inputs. Decay kinetics for IPSCs were severalfold faster than for glycinergic synaptic events reported previously. At physiological temperatures in P25 rats, IPSCs decayed in approximately 1 msec and could be elicited at frequencies up to 500 Hz. Moreover, EPSPs triggered by glutamatergic signals derived from the calyx or simulated by conductance clamp were suppressed when preceded by simulated glycinergic IPSPs. The matching of excitatory transmission in the calyx of Held by a powerful, precision inhibitory system suggests that the relay function of the MNTB may be rapidly modified during sound localization.

Figure 1.

Development of powerful glycinergic IPSCs. A, Nearly complete block of an IPSC in a P19 rat by 0.5 μm strychnine. Inset, Percentage block by SR-95531 (SR) and strychnine (STR) for P19–P25 rats. B, Current–voltage relationship for a single IPSC. Voltage range is –60 to +30 mV. C, D, Examples of IPSCs from P14 and P25 rats, respectively. Inset in C shows average data for the indicated ages. Calibration in D applies also to C.

Figure 2.

IPSCs at physiological temperatures. Ai, Examples of evoked IPSCs at room temperature (RT) versus 37°C. Exponential fits to decays are shown with dominant time constants indicated. Aii shows mean amplitude and decay constants for evoked events at two temperatures. Bi, Bii, Examples and average data for mIPSCs at room temperature and 37°C. Ci, Example of IPSCs evoked at 500 Hz. Cii, Average data for four neurons showing peak (circles) and baseline currents (squares) during a train of 10 stimuli at 500 Hz.

Figure 3.

Electrical interaction between glutamatergic and glycinergic signals. A, Examples illustrating the relative size of IPSCs and EPSCs for equivalent absolute driving force. Bi–Biii, Shunting of calyceal EPSP by simulated IPSG. Bi, A suprathreshold and a shunted EPSP. Bii, The injected current from the conductance clamp. Biii, The conductance waveform and timing of synaptic stimulus. Dashed line indicates spike threshold. C, An action potential (gray trace) scaled and superimposed on its first derivative (black). Arrow indicates the point of inflection at which an EPSP gives rise to a spike and is accentuated by the sudden change in derivative slope. Voltage at this point was defined as threshold.