Abstract
The inferior colliculus (IC) receives ascending excitatory and inhibitory inputs from multiple sources, but how these auditory inputs converge to generate IC spike patterns is poorly understood. Simulating patterns of in vivo spike train data from cellular and synaptic models creates a powerful framework to identify factors that contribute to changes in IC responses, such as those resulting in age-related loss of temporal processing. A conductance-based single neuron IC model was constructed, and its responses were compared to those observed during in vivo IC recordings in rats. IC spike patterns were evoked using amplitude-modulated tone or noise carriers at 20–40 dB above threshold and were classified as low-pass, band-pass, band-reject, all-pass, or complex based on their rate modulation transfer function tuning shape. Their temporal modulation transfer functions were also measured. These spike patterns provided experimental measures of rate, vector strength, and firing pattern for comparison with model outputs. Patterns of excitatory and inhibitory synaptic convergence to IC neurons were based on anatomical studies and generalized input tuning for modulation frequency. Responses of modeled ascending inputs were derived from experimental data from previous studies. Adapting and sustained IC intrinsic models were created, with adaptation created via calcium-activated potassium currents. Short-term synaptic plasticity was incorporated into the model in the form of synaptic depression, which was shown to have a substantial effect on the magnitude and time course of the IC response. The most commonly observed IC response sub-types were recreated and enabled dissociation of inherited response properties from those that were generated in IC. Furthermore, the model was used to make predictions about the consequences of reduction in inhibition for age-related loss of temporal processing due to a reduction in GABA seen anatomically with age.
Highlights
The inferior colliculus (IC) is a major integrative center of auditory processing, receiving multiple ascending excitatory inputs from the contralateral ventral and dorsal cochlear nuclei (VCN and DCN, respectively) and from the contralateral lateral and medial superior olive (LSO and MSO) to form different functional zones within the IC
CONCLUDING REMARKS The IC model presented here, using realistic voltage-dependent membrane channels and synaptic ion channels, is able to produce all in-vivo rMTF responses described in this study (Figures 4, 5)
There was an intermediate regime between LP and AP responses (Figures 7A–F) where AP inputs (VCN, DCN) coupled with DNLL inhibition produced BR responses
Summary
The inferior colliculus (IC) is a major integrative center of auditory processing, receiving multiple ascending excitatory inputs from the contralateral ventral and dorsal cochlear nuclei (VCN and DCN, respectively) and from the contralateral lateral and medial superior olive (LSO and MSO) to form different functional zones within the IC (reviewed in Kelly and Caspary, 2005). These excitatory input patterns are superimposed upon similar functional zones formed by the inhibitory dorsal and ventral nuclei of the lateral lemniscus (DNLL and VNLL), as well as the superior olivary nucleus (Cant and Benson, 2006; Loftus et al, 2010). This complex interplay of excitatory and inhibitory projections from various nuclei of the auditory pathway makes the IC an important nucleus for understanding how neural representations are transformed as they ascend the auditory pathway
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