Essential role for plasma membrane glutamate transporters in stimulus intensity coding in auditory neurons

Plasma membrane glutamate transporters, also known as excitatory amino acid transporters (EAATs), serve to remove glutamate from extracellular spaces following transmitter release. Generally, this process is slow enough that EAAT activity controls the levels of background glutamate rather than the magnitude and time course of synaptic responses. We show here a striking exception to this pattern in the auditory system where neurons receive ongoing high-frequency synaptic signals. The effect of blocking EAATs on synaptic function was tested in neurons of the ventral cochlear nucleus in brain slices from mouse, focusing on auditory nerve inputs to T-stellate cells, neurons used to encode the spectrum of complex sounds. Complete block of EAATs caused a gradual accumulation of glutamate leading to a large depolarization in T-stellate cells and cessation of excitability. Partial EAAT blockade maintained resting potential but severely compromised the ability of the neurons to linearly encode the frequency of presynaptic spike activity with changes in postsynaptic firing, an essential feature of T-stellate cell function in sound intensity coding. After EAAT blockade, even a few high-frequency presynaptic spikes were sufficient to accumulate glutamate and cause repetitive postsynaptic firing lasting for tens to hundreds of milliseconds. Both glial and neuronal transporters were found to contribute to this rapid uptake necessary to maintain normal synaptic transmission. Altering the number of active auditory nerve fibers revealed that glutamate did not spill over between bouton synapses made by different nerve fibers, suggesting that synaptic boutons onto T-stellate cells restrict the diffusion of glutamate, necessitating an enhanced, local uptake activity. Notably, spike coding by the giant endbulb synapses on bushy cells was little affected by EAAT blockade, indicating a cell-type specificity to rapid glutamate uptake. Thus, rapid glutamate uptake enables the intensity coding function of neurons within the auditory system.