The role of A1-MGBv corticothalamic feedback explored with mistuning of harmonic complex tones using ferrets

The A1-MGBv corticothalamic projection is one of the major descending pathways in the auditory system, projecting from the primary auditory cortex (A1) to the ventral division of medial geniculate body (MGBv). Recent evidence suggests that corticothalamic feedback can sharpen the spectral receptive fields of thalamic neurons and modulate the temporal precision of the responses. The aim of the work presented here was to investigate the role of A1-MGBv corticothalamic feedback using harmonic and mistuned complex tones (HCTs and MCTs) in adult ferrets. The MCTs used comprised a mistuned harmonic shifted to a higher frequency in the otherwise HCTs. The harmonic structure of sounds is an important grouping cue in auditory scene analysis. We first measured the ability of ferrets to detect mistuned harmonics using a go/no-go behavioural task paradigm. Psychometric functions plotting sensitivity as a function of degree of mistuning were used to evaluate the behavioural performance using signal detection theory. The threshold for mistuning detection was 0.8 ± 0.1 Hz (mean ± sem), with sensitivity indices and reaction times depending on the degree of mistuning. The threshold range for mistuning in ferrets is similar to that previously described in other species. The responses to MCTs in MGBv neurons were explored using extracellular recordings in anaesthetised animals. The functional organization of the ferret auditory thalamus has not previously been investigated. The ferret MGBv was identified by the short response latency and the sharply tuned frequency response areas of the recorded units and by its tonotopic organization, which was found to be comparable to that of other species. Compared to their responses to HCTs, the firing rates of MGBv neurons were modulated depending on the degree of mistuning and the fundamental frequency of the MCTs. Distinctive temporal response patterns were also observed, phase locked to the periodicities of altered phases of the MCTs. To investigate whether corticofugal modulation contributes to mistuning detection, A1-MGBv corticothalamic neurons were selectively eliminated bilaterally by chromophore-targeted laser photolysis. Using the behavioural paradigm established above, mistuning detection was tested before and after these lesions were made. Animals with corticothalamic lesions were impaired in their ability to detect a mistuned harmonic, as indicated by decreased d’ values, increased thresholds, and a shift of the psychometric curves towards higher mistuning values. Together, these results suggest a possible role for corticothalamic feedback in modulating the firing patterns of MGBv neurons in ways that contribute to accurate recognition of complex auditory stimuli. In other words, this top-down corticothalamic feedback may be important for auditory scene analysis.