Although the brain relies on auditory information to calibrate vocal behavior, the neural substrates of vocal learning remain unclear. Here we demonstrate that lesions of the dopaminergic inputs to a basal ganglia nucleus in a songbird species (Bengalese finches, Lonchura striata var. domestica) greatly reduced the magnitude of vocal learning driven by disruptive auditory feedback in a negative reinforcement task. These lesions produced no measureable effects on the quality of vocal performance or the amount of song produced. Our results suggest that dopaminergic inputs to the basal ganglia selectively mediate reinforcement-driven vocal plasticity. In contrast, dopaminergic lesions produced no measurable effects on the birds' ability to restore song acoustics to baseline following the cessation of reinforcement training, suggesting that different forms of vocal plasticity may use different neural mechanisms.

The polycistronic miR-183/96/182 cluster is preferentially and abundantly expressed in terminally differentiating sensory epithelia. To clarify its roles in the terminal differentiation of sensory receptors in vivo, we deleted the entire gene cluster in mouse germline through homologous recombination. The miR-183/96/ 182 null mice display impairment of the visual, auditory, vestibular, and olfactory systems, attributable to profound defects in sensory receptor terminal differentiation. Maturation of sensory receptor precursors is delayed, and they never attain a fully differentiated state. In the retina, delay in up-regulation of key photoreceptor genes underlies delayed outer segment elongation and possibly mispositioning of cone nuclei in the retina. Incomplete maturation of photoreceptors is followed shortly afterward by early-onset degeneration. Cell biologic and transcriptome analyses implicate dysregulation of ciliogenesis, nuclear translocation, and an epigenetic mechanism that may control timing of terminal differentiation in developing photoreceptors. In both the organ of Corti and the vestibular organ, impaired terminal differentiation manifests as immature stereocilia and kinocilia on the apical surface of hair cells. Our study thus establishes a dedicated role of the miR-183/96/182 cluster in driving the terminal differentiation of multiple sensory receptor cells. M ammalian sensory epithelia, such as those underlying vison, hearing, smell, and balance, consist of ciliated sensory receptor cells. Although highly specialized, similarities in embryonic origin underlie common features in their development (1). Following specification, lineage-restricted postmitotic precursors become structurally and functionally mature through a series of cellular differentiation events, collectively described as terminal differentiation (2). During maturation, sensory receptor cells typically develop microtubule-based primary cilia and in some cases actin-based membrane protrusions on apical membranes, which are sensory organelles, while maintaining apical basal polarity within sensory epithelia. In photoreceptors, for example, the extension of outer segments (OSs), specialized sensory cilia, is central to postmitotic differentiation and necessary for light sensitivity (3). In auditory and vestibular hair cells, the proper formation of hair bundles is indispensable for detecting sound and head positions (4). Similarly, olfactory sensory neurons (OSNs), the odorant receptor cells in the olfactory epithelium, project multiple dendritic cilia into the mucous membrane of the nasal epithelium where olfactory signaling is initiated (5). Mature sensory epithelia are highly structured with specific spatial organization that is tied to their functions. Synchronized planar cell polarity (PCP) of hair cells in the inner ear, for example, provides their directional sensitivity (6), whereas the development of laminar architecture in the retina restricts photoreceptors to proper compartments for efficient wiring with secondary neuro...

The N-methyl-D-aspartate receptor (NMDAR) is thought to be essential for synaptic plasticity and learning. However, recent work indicates that the role of this receptor depends on the prior history of the research subject. For example, animals trained on a hippocampus-dependent learning task are subsequently able to acquire new information in the absence of NMDAR activation. The current experiments were designed to identify the types of experiences that lead to NMDAR-independent learning. Using contextual fear conditioning in mice, we find that NMDAR-independent learning is only observed when (1) animals are trained on the same behavioral task and (2) initial learning is successfully encoded into long-term memory.

Motor learning is a core aspect of human life, and appears to be ubiquitous throughout the animal kingdom. Dopamine, a neuromodulator with a multifaceted role in synaptic plasticity, may be a key signaling molecule for motor skill learning. Though typically studied in the context of reward-based associative learning, dopamine appears to be necessary for some types of motor learning. Mesencephalic dopamine structures are highly conserved among vertebrates, as are some of their primary targets within the basal ganglia, a subcortical circuit important for motor learning and motor control. With a focus on the benefits of cross-species comparisons, this review examines how "model-free" and "model-based" computational frameworks for understanding dopamine's role in associative learning may be applied to motor learning. The hypotheses that dopamine could drive motor learning either by functioning as a reward prediction error, through passive facilitating of normal basal ganglia activity, or through other mechanisms are examined in light of new studies using humans, rodents, and songbirds. Additionally, new paradigms that could enhance our understanding of dopamine's role in motor learning by bridging the gap between the theoretical literature on motor learning in humans and other species are discussed.

The olfactory system depends upon organizational maps that are developmentally refined and maintained, however the cellular and molecular mechanisms that underlie these processes are unknown. Studies have shown that microglia and complement molecules are important for the developmental refinement of circuitry within the visual system, thus we asked whether they played a similar role in the olfactory system through the formation of the olfactory bulb (OB) maps, the glomerular and intrabulbar maps. Our findings revealed that microglia in mature animals