A neural circuit mechanism for regulating vocal variability during song learning in zebra finches

Motor skill learning is characterized by improved performance and reduced motor variability. The neural mechanisms that couple skill level and variability, however, are not known. The zebra finch, a songbird, presents a unique opportunity to address this question because production of learned song and induction of vocal variability are instantiated in distinct circuits that converge on a motor cortex analogue controlling vocal output. To probe the interplay between learning and variability, we made intracellular recordings from neurons in this area, characterizing how their inputs from the functionally distinct pathways change throughout song development. We found that inputs that drive stereotyped song-patterns are strengthened and pruned, while inputs that induce variability remain unchanged. A simple network model showed that strengthening and pruning of action-specific connections reduces the sensitivity of motor control circuits to variable input and neural ‘noise’. This identifies a simple and general mechanism for learning-related regulation of motor variability. DOI: http://dx.doi.org/10.7554/eLife.03697.00

LEARNING-RELATED CHANGES IN THE FUNCTIONAL CONNECTIVITY WITHIN THE ZEBRA FINCH SONG-CONTROL CIRCUIT

Many species-specific sensorimotor behaviors, such as speech in humans, emerge from the interplay between genetically defined developmental programs and sensory experience. How these processes interact during learning to shape motor circuits is not well understood. The zebra finch (Taeniopygia guttata), an oscine bird that learns to imitate the song of its tutor (usually the father), provides a uniquely tractable model for exploring this question. Song learning in zebra finches takes place during a discrete three-month period during which male juveniles progress from producing highly variable rudimentary sounds that are noisy and unstructured, to a highly stereotyped imitation of their tutor's song. Here I characterize learning-related changes in the functional connectivity within a motor cortex-analogue brain area (RA) that control song production

GluN2D-mediated excitatory drive onto medial prefrontal cortical PV+ fast-spiking inhibitory interneurons.

Deficits in fast-spiking inhibitory interneurons (FSINs) within the dorsolateral prefrontal cortex (dlPFC) are hypothesized to underlie cognitive impairment associated with schizophrenia. Though representing a minority of interneurons, this key cell type coordinates broad neural network gamma-frequency oscillations, associated with cognition and cognitive flexibility. Here we report expression of GluN2D mRNA selectively in parvalbumin positive cells of human postmortem dlPFC tissue, but not pyramidal neurons, with little to no GluN2C expression in either cell type. In acute murine mPFC slices the GluN2C/D selective positive allosteric modulator (PAM), CIQ(+), increased the intrinsic excitability as well as enhanced NMDAR-mediated EPSCs onto FSINs. This increase in intrinsic excitability with GluN2C/D PAM was also observed in the Dlx 5/6+/- FSIN developmental deficit model with reported FSIN hypoexcitability. Together these data speak to selective modulation of FSINs by a GluN2D PAM, providing a potential mechanism to counter the FSIN-deficit seen in schizophrenia