Experience-Dependent Intrinsic Plasticity During Auditory Learning.

Song learning in zebra finches (Taeniopygia guttata) requires exposure to the song of a tutor, resulting in an auditory memory. This memory is the foundation for later sensorimotor learning, resulting in the production of a copy of the tutor's song. The cortical premotor nucleus HVC (proper name) is necessary for auditory and sensorimotor learning as well as the eventual production of adult song. We recently discovered that the intrinsic physiology of HVC neurons changes across stages of song learning, but are those changes the result of learning or are they experience-independent developmental changes? To test the role of auditory experience in driving intrinsic changes, patch-clamp experiments were performed comparing HVC neurons in juvenile birds with varying amounts of tutor exposure. The intrinsic physiology of HVC neurons changed as a function of tutor exposure. Counterintuitively, tutor deprivation resulted in juvenile HVC neurons showing an adult-like phenotype not present in tutor-exposed juveniles. Biophysical models were developed to predict which ion channels were modulated by experience. The models indicate that tutor exposure transiently suppressed the Ih and T-type Ca2+ currents in HVC neurons that target the basal ganglia, whereas tutor exposure increased the resting membrane potential and decreased the spike amplitude in HVC neurons that drive singing. Our findings suggest that intrinsic plasticity may be part of the mechanism for auditory learning in the HVC. More broadly, models of learning and memory should consider intrinsic plasticity as a possible mechanism by which the nervous system encodes the lasting effects of experience.SIGNIFICANCE STATEMENT It is well established that learning involves plasticity of the synapses between neurons. However, the activity of a neural circuit can also be dramatically altered by changes in the intrinsic properties (ion channels) of the component neurons. The present experiments show experience-dependent changes in the intrinsic physiology of neurons in the cortical premotor nucleus HVC (proper name) in juvenile zebra finches (Taeniopygia guttata) during auditory learning of a tutor's song. Tutor deprivation does not "arrest" development of intrinsic properties, but rather results in neurons with a premature adult-like physiological phenotype. It is possible that auditory learning involves a form of nonsynaptic plasticity and that experience-dependent suppression of specific ion channels may work in concert with synaptic plasticity to promote vocal learning.

Neuronal Intrinsic Physiology Changes During Development of a Learned Behavior.

Juvenile male zebra finches learn their songs over distinct auditory and sensorimotor stages, the former requiring exposure to an adult tutor song pattern. The cortical premotor nucleus HVC (acronym is name) plays a necessary role in both learning stages, as well as the production of adult song. Consistent with neural network models where synaptic plasticity mediates developmental forms of learning, exposure to tutor song drives changes in the turnover, density, and morphology of HVC synapses during vocal development. A network's output, however, is also influenced by the intrinsic properties (e.g., ion channels) of the component neurons, which could change over development. Here, we use patch clamp recordings to show cell-type-specific changes in the intrinsic physiology of HVC projection neurons as a function of vocal development. Developmental changes in HVC neurons that project to the basal ganglia include an increased voltage sag response to hyperpolarizing currents and an increased rebound depolarization following hyperpolarization. Developmental changes in HVC neurons that project to vocal-motor cortex include a decreased resting membrane potential and an increased spike amplitude. HVC interneurons, however, show a relatively stable range of intrinsic features across vocal development. We used mathematical models to deduce possible changes in ionic currents that underlie the physiological changes and to show that the magnitude of the observed changes could alter HVC circuit function. The results demonstrate developmental plasticity in the intrinsic physiology of HVC projection neurons and suggest that intrinsic plasticity may have a role in the process of song learning.

Electrophysiological characterization and computational models of HVC neurons in the zebra finch.

The nucleus HVC (proper name) within the avian analog of mammal premotor cortex produces stereotyped instructions through the motor pathway leading to precise, learned vocalization by songbirds. Electrophysiological characterization of component HVC neurons is an important requirement in building a model to understand HVC function. The HVC contains three neural populations: neurons that project to the RA (robust nucleus of arcopallium), neurons that project to Area X (of the avian basal ganglia), and interneurons. These three populations are interconnected with specific patterns of excitatory and inhibitory connectivity, and they fire with characteristic patterns both in vivo and in vitro. We performed whole cell current-clamp recordings on HVC neurons within brain slices to examine their intrinsic firing properties and determine which ionic currents are responsible for their characteristic firing patterns. We also developed conductance-based models for the different neurons and calibrated the models using data from our brain slice work. These models were then used to generate predictions about the makeup of the ionic currents that are responsible for the different responses to stimuli. These predictions were then tested and verified in the slice using pharmacological manipulations. The model and the slice work highlight roles of a hyperpolarization-activated inward current (Ih), a low-threshold T-type Ca(2+) current (ICa-T), an A-type K(+) current (IA), a Ca(2+)-activated K(+) current (ISK), and a Na(+)-dependent K(+) current (IKNa) in driving the characteristic neural patterns observed in the three HVC neuronal populations. The result is an improved characterization of the HVC neurons responsible for song production in the songbird.

Axial organization of a brain region that sequences a learned pattern of behavior.

Neural activity within HVC (proper name), a premotor nucleus of the songbird telencephalon analogous to premotor cortical regions in mammals, controls the temporal structure of learned song in male zebra finches (Taeniopygia guttata). HVC is composed of a superficially isomorphic neuronal mosaic, implying that song is encoded in a distributed network within HVC. Here, we combined HVC microlesions (10% focal ablation) with singing-driven immediate-early gene (IEG) labeling to explore the network architecture of HVC during singing. Microlesions produce a transient disruption of HVC activity that results in a temporary (≈ 1 week) loss of vocal patterning. Results showed an asymmetrical reduction in the density of IEG-labeled cells 3-5 d after microlesions: swaths of unlabeled cells extended rostrally and/or caudally depending on the position of the HVC microlesion. Labeling returned once birds recovered their songs. Axial swaths of unlabeled cells occurred whether microlesions were located at rostral or caudal poles of HVC, indicating that the localized reduction in IEG labeling could not be attributable solely to transection of afferents that enter HVC rostrally. The asymmetrical pattern of reduced IEG labeling could be explained if synaptic connectivity within HVC is organized preferentially within the rostrocaudal axis. In vivo retrograde tracer injections and in vitro stimulation and recording experiments in horizontal slices of HVC confirmed a rostrocaudal organization of HVC neural connectivity. Our findings suggest that HVC contains an axially organized network architecture that may encode the temporal structure of song.