First, while previous studies in songbirds (Keller and Hahnloser, 2009 and Lei and Mooney, 2010) and marmosets (Eliades this website and

Wang, 2003, Eliades and Wang, 2005 and Eliades and Wang, 2008) have detected neurons in auditory areas that are sensitive to perturbation of vocalization-related auditory feedback, this study provides the first observation of sensitivity to deafening in any song sensorimotor area and, to our knowledge, offers the first description of the synaptic effects of hearing loss in sensorimotor neurons important to vocal control. Second, deafening selectively affects spines on HVCX neurons, and changes in spine size precede and predict song degradation, implicating HVCX neurons in the processing of auditory feedback-related information. Third, structural changes to dendritic spines were accompanied by functional changes in synaptic strength, intrinsic excitability, and spontaneous action potential output of HVCX neurons, raising the possibility that deafening ultimately affects the singing-related action KPT-330 potential output of these cells. Taken together, these findings indicate

that HVCX neurons are sensitive to deafening and implicate the input stage to the AFP in the processing of feedback-related information. While previous studies employing chronic electrophysiological recordings failed to detect feedback-driven changes in the singing-related activity of HVCX neurons (Kozhevnikov and Fee, 2007 and Prather et al., 2008), in vivo imaging permitted detection of subtle changes in HVCX dendritic spines within the first few days of deafening. By tracking dendritic spines on single HVC neurons, it was possible to characterize the cell-type specificity and time course of deafening-induced changes in synapses with a degree of precision that would be difficult to achieve using electrophysiological methods. However, these findings do not exclude the possibility Metalloexopeptidase that other cells and synapses within HVC are also affected by deafening. Indeed, a previous study in Bengalese finches found that the action potential output of putative HVC interneurons changes subtly and rapidly (∼20 ms)

following acute feedback perturbation (Sakata and Brainard, 2008), raising the possibility that synapses on this cell type are sensitive to deafening in zebra finches. Further, although the structural and functional measurements performed here support the idea that deafening weakens excitatory and inhibitory synapses on HVCX neurons, inhibitory synapses may also change on HVCRA neurons following deafening. Finally, our findings support the idea that deafening-induced changes propagate into HVC but do not exclude the possibility that other song system neurons are sensitive to feedback perturbation. Regardless of these additional possibilities, the fact that structural changes to dendritic spines occurred only in HVCX neurons supports the idea that synapses on this cell type are especially sensitive to deafening.