Deafening Drives Cell-Type-Specific Changes to Dendritic Spines in a Sensorimotor Nucleus Important to Learned Vocalizations

Abstract

Summary Hearing loss prevents vocal learning and causes learned vocalizations to deteriorate, but how vocalization-related auditory feedback acts on neural circuits that control vocalization remains poorly understood. We deafened adult zebra finches, which rely on auditory feedback to maintain their learned songs, to test the hypothesis that deafening modifies synapses on neurons in a sensorimotor nucleus important to song production. Longitudinal in vivo imaging revealed that deafening selectively decreased the size and stability of dendritic spines on neurons that provide input to a striatothalamic pathway important to audition-dependent vocal plasticity, and changes in spine size preceded and predicted subsequent vocal degradation. Moreover, electrophysiological recordings from these neurons showed that structural changes were accompanied by functional weakening of both excitatory and inhibitory synapses, increased intrinsic excitability, and changes in spontaneous action potential output. These findings shed light on where and how auditory feedback acts within sensorimotor circuits to shape learned vocalizations.

Synapse-specific and size-dependent mechanisms of spine structural plasticity accompanying synaptic weakening

“…Several studies demonstrate key roles for mGluRs in regulating experience-dependent circuit plasticity in response to visual experience (40,41), fear conditioning (42), and somatosensory experience (9,43). Moreover, recent studies of mGluR-dependent synaptic plasticity have led to the discovery of novel cellular and molecular mechanisms with implications for diseases such as Fragile X syndrome and Alzheimer's disease (26,44,45).…”

“…Indeed, spine elimination occurs more frequently than does spine formation in young rodents between the first and the third month of age (3)(4)(5), a period when experience-dependent refinement of neural circuitry is in its peak. Furthermore, several in vivo studies demonstrate that manipulations leading to experience-dependent circuit plasticity also increase the rate of spine shrinkage and loss (6)(7)(8)(9). However, it remains unclear how neural activity drives the selective shrinkage and loss of individual dendritic spines in response to sensory experience.…”

“…Small spines are in general more motile and thought to serve as substrates for plasticity, or "learning" spines; large spines are more stable and thought to serve as components of functioning neural circuits, or "memory" spines (12,14). It is the selective shrinkage and loss of individual circuit-incorporated, persistent spines that underlies experience-dependent circuit refinement (6,9,15). Thus, experience-dependent circuit remodeling requires an activity-dependent mechanism that selectively induces shrinkage and retraction of those specific individual dendritic spines that are no longer useful for circuit function.…”

Adult Neurogenesis in the Songbird: Region-Specific Contributions of New Neurons to Behavioral Plasticity and Stability

“…HVC-RA neurons, in particular, have been suggested to provide a metronome-like function in maintaining the precise temporal structure underlying the acoustic unfolding of the song [Hahnloser et al, 2002;Long and Fee, 2008]. At a higher-order level, it has been suggested that the vocal motor pathway more generally promotes song stability [Thompson and Johnson, 2007] relative to the anterior forebrain pathway, which in turn confers song variability [Brainard and Doupe, 2000;Nordeen and Nordeen, 2010;Tschida and Mooney, 2012]. Any of these roles is consistent with the idea that more HVC-RA neurons may correspond to greater song stability.…”

Ultrastructural and electrophysiological analysis of Area X in the untutored and deafened Bengalese finch in relation to normally reared birds

“…It has been shown that deafening adult songbirds decreases the amplitude of spontaneous synaptic activity, alters spontaneous action potential activity in HVC X neurons, and selectively decreases their dendritic spine sizes and stability (Tschida and Mooney, 2012). These changes precede and predict subsequent birdsong degradation.…”