NMDA Currents Modulate the Synaptic Input–Output Functions of Neurons in the Dorsal Nucleus of the Lateral Lemniscus in Mongolian Gerbils

Abstract

Neurons in the dorsal nucleus of the lateral lemniscus (DNLL) receive excitatory and inhibitory inputs from the superior olivary complex (SOC) and convey GABAergic inhibition to the contralateral DNLL and the inferior colliculi. Unlike the fast glycinergic inhibition in the SOC, this GABAergic inhibition outlasts auditory stimulation by tens of milliseconds. Two mechanisms have been postulated to explain this persistent inhibition. One, an "integration-based" mechanism, suggests that postsynaptic excitatory integration in DNLL neurons generates prolonged activity, and the other favors the synaptic time course of the DNLL output itself. The feasibility of the integrationbased mechanism was tested in vitro in DNLL neurons of Mongolian gerbils by quantifying the cellular excitability and synaptic inputoutput functions (IO-Fs). All neurons were sustained firing and generated a near monotonic IO-F on current injections. From synaptic stimulations, we estimate that activation of approximately five fibers, each on average liberating ϳ18 vesicles, is sufficient to trigger a single postsynaptic action potential. A strong single pulse of afferent fiber stimulation triggered multiple postsynaptic action potentials. The steepness of the synaptic IO-F was dependent on the synaptic NMDA component. The synaptic NMDA receptor current defines the slope of the synaptic IO-F by enhancing the temporal and spatial EPSP summation. Blocking this NMDA-dependent amplification during postsynaptic integration of train stimulations resulted into a ϳ20% reduction of the decay time course of the GABAergic inhibition. Thus, our data show that the NMDA-dependent amplification of the postsynaptic activity contributes to the GABAergic persistent inhibition generated by DNLL neurons.

Development and modulation of intrinsic membrane properties control the temporal precision of auditory brain stem neurons

“…These membrane parameters were analyzed from the average voltage response to 40 -60 repetitions of 200 ms-long step current injections of Ϫ10 pA ( Fig. 1A; n ϭ 75) (Ammer et al 2012;Berger et al 2014;Couchman et al 2010;Porres et al 2011). The use of such a small current amplitude kept the resulting voltage deflection minimal and hence minimized the activation or deactivation of additional voltage-dependent conductances close to the neuron's resting state.…”

“…So far, we characterized the developmental changes and relative contributions of passive and active conductances to the firing pattern using step protocols between 200 and 500 ms. However, action potentials in the auditory brain stem are usually triggered by 0.5-2 ms fast synaptic ␣-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid conductances (Ammer et al 2012;Couchman et al 2010;Porres et al 2011;Taschenberger and von Gersdorff 2000;Yang and Xu-Friedman 2009) rather than by prolonged depolarization plateaus. Thus the development of the relevant action-potential properties cannot be extracted using long current injections.…”

Functional localization of neurotransmitter receptors and synaptic inputs to mature neurons of the medial superior olive

“…Although NMDARs are strongly developmentally downregulated in the ITD circuit (Futai et al 2001;Zhou and Parks 1993), recent work indicates that NMDARs still play a functional role at mature stages (Caicedo and Eybalin 1999;Porres et al 2011;Steinert et al 2010). To investigate a possible contribution at mature MSO cells, functional NMDAR expression was mapped along their dendrites with UV uncaging of MNI-Glu (n ϭ 14, P30 -35).…”

The role of negative conductances in neuronal subthreshold properties and synaptic integration

“…For example, Fricker and Miles (2000) showed a decrease in EPSP area when blocked by AP5 in hippocampal pyramidal cells, and Connelly et al (2016) showed strong EPSP amplification by NMDA currents in thalamocortical neurons. In addition, Porres et al (2011) observed an EPSP decay phase prolongation in neurons of the dorsal nucleus of the lateral lemniscus caused by NMDA currents.…”