Afferent stimulus strengths were adjusted in these experiments so

Afferent stimulus strengths were adjusted in these experiments so that bilateral EPSPs remained subthreshold (Figures S3A and S3C). In both the absence and presence of inhibition, subthreshold summation was remarkably linear, nearly matching the summation predicted from the arithmetic sums of average PSP waveforms (Figures 6E and 6F). ITD functions were generated by measuring the maximal depolarization attained during each coincidence trial

(Figures S3B and S3D). Lacking a MEK pathway threshold mechanism to select for the largest events, subthreshold ITD functions were broader and flatter than spike-based ITD functions. Similar to the spiking responses, inhibition did not alter the mean or median mass of ITD functions (Figures S3E and S3F), whereas physiological inhibition and its hyperpolarizing component significantly decreased the peak and half-width of subthreshold ITD functions (Figures S3G and S3H). These results suggest that the effects of inhibition on spike probability ITD functions are a direct reflection of how inhibition shapes subthreshold summation. ITD computations are usually made within the phase-locking range of input neurons, which extends up to ∼2 kHz (Johnson, 1980; Joris et al., 1994). Given that even brief

sounds generate multiple stimulus cycles, the duration of IPSPs suggests Selleck ZVADFMK that they will sum at higher frequencies, possibly complicating synaptic coincidence detection. To test whether IPSPs sum, we recorded from MSO neurons while using stimulating electrodes to evoke 100–800 Hz trains of ten ipsilateral or contralateral IPSPs. Both ipsilateral and contralateral IPSPs showed clear evidence of temporal summation (Figures 7A and 7B). We quantified Florfenicol this by measuring the amount the membrane potential was hyperpolarized relative to rest at the foot of each IPSP and comparing this to the peak amplitude of the first IPSP in the train. This showed that there was significant summation of ipsilateral IPSPs at frequencies of 300 Hz and greater (Figure 7C) and of contralateral IPSPs at frequencies of 200 Hz and greater (Figure 7D).

Under in vivo conditions, in which inhibition is presumably binaural and subject to more temporal jitter than observed with local afferent stimulation in slice, the summation of IPSPs is probably even greater than observed here. The presence of this summation suggests that IPSPs occurring later in a train will contribute to the temporal dynamics of coincidence detection differently than earlier IPSPs. We also examined how the peak amplitudes of IPSPs, as measured from the foot to the peak of each event, varied during the train relative to the amplitude of the first event. Previous studies have found that IPSCs undergo significant short-term depression during repetitive stimuli at frequencies as low as 0.5 Hz (Couchman et al., 2010; Fischl et al., 2012).

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