No abstract

Sequences of motor activity are encoded in many vertebrate brains by complex spatio-temporal patterns of neural activity; however, the neural circuit mechanisms underlying the generation of these pre-motor patterns are poorly understood. In songbirds, one prominent site of pre-motor activity is the forebrain robust nucleus of the archistriatum (RA), which generates stereotyped sequences of spike bursts during song and recapitulates these sequences during sleep. We show that the stereotyped sequences in RA are driven from nucleus HVC (high vocal centre), the principal pre-motor input to RA. Recordings of identified HVC neurons in sleeping and singing birds show that individual HVC neurons projecting onto RA neurons produce bursts sparsely, at a single, precise time during the RA sequence. These HVC neurons burst sequentially with respect to one another. We suggest that at each time in the RA sequence, the ensemble of active RA neurons is driven by a subpopulation of RA-projecting HVC neurons that is active only at that time. As a population, these HVC neurons may form an explicit representation of time in the sequence. Such a sparse representation, a temporal analogue of the 'grandmother cell' concept for object recognition, eliminates the problem of temporal interference during sequence generation and learning attributed to more distributed representations.

Songbirds learn their songs by trial-and-error experimentation, producing highly variable vocal output as juveniles. By comparing their own sounds to the song of a tutor, young songbirds gradually converge to a stable song that can be a remarkably good copy of the tutor song. Here we show that vocal variability in the learning songbird is induced by a basal-ganglia-related circuit, the output of which projects to the motor pathway via the lateral magnocellular nucleus of the nidopallium (LMAN). We found that pharmacological inactivation of LMAN dramatically reduced acoustic and sequence variability in the songs of juvenile zebra finches, doing so in a rapid and reversible manner. In addition, recordings from LMAN neurons projecting to the motor pathway revealed highly variable spiking activity across song renditions, showing that LMAN may act as a source of variability. Lastly, pharmacological blockade of synaptic inputs from LMAN to its target premotor area also reduced song variability. Our results establish that, in the juvenile songbird, the exploratory motor behavior required to learn a complex motor sequence is dependent on a dedicated neural circuit homologous to cortico-basal ganglia circuits in mammals.

Summary Many complex behaviors, like speech or music, have a hierarchical organization with structure on many timescales. How does the brain control the timing of behavioral sequences? Do different circuits control different timescales of the behavior? To address these questions, we use temperature to manipulate the biophysical dynamics in different regions of the songbird forebrain involved in song production. We found that cooling premotor nucleus HVC (proper name) slows song speed across all timescales by up to 45% while only slightly altering the acoustic structure, whereas cooling downstream motor nucleus RA (robust nucleus of the arcopallium) has no observable effect on song timing. Our observations suggest that dynamics within HVC are involved in the control of song timing, perhaps through a chain-like organization. Local manipulation of brain temperature should be broadly applicable to identify neural circuitry that controls the timing of behavioral sequences and, more generally, to study the origin and role of oscillatory and other forms of brain dynamics in neural systems.

SummaryIn songbirds, the remarkable temporal precision of song is generated by a sparse sequence of bursts in the premotor nucleus HVC (proper name). To distinguish between two possible classes of models of neural sequence generation, we carried out intracellular recordings of HVC neurons in singing birds. We found that the subthreshold membrane potential is characterized by a large rapid depolarization 5–10 ms prior to burst onset, consistent with a synaptically-connected chain of neurons in HVC. We found no evidence for the slow membrane potential modulation predicted by models in which burst timing is controlled by subthreshold dynamics. Furthermore, bursts ride on an underlying depolarization of ~10ms duration, likely the result of a regenerative calcium spike within HVC neurons that could facilitate the propagation of activity through a chain network with high temporal precision. Our results shed light on the fundamental mechanisms by which neural circuits can generate complex sequential behaviours.

In songbirds, as in mammals, basal ganglia-forebrain circuits are necessary for the learning and production of complex motor behaviors; however, the precise role of these circuits remains unknown. It has recently been shown that a basal ganglia-forebrain circuit in the songbird, which projects directly to vocal-motor circuitry, has a premotor function driving exploration necessary for vocal learning. It has also been hypothesized that this circuit, known as the anterior forebrain pathway (AFP), may generate an instructive signal that improves performance in the motor pathway. Here, we show that the output of the AFP directly implements a motor correction that reduces vocal errors. We use disruptive auditory feedback, contingent on song pitch, to induce learned changes in song structure over the course of hours and find that reversible inactivation of the output of the AFP produces an immediate regression of these learned changes. Thus, the AFP is involved in generating an error-reducing bias, which could increase the efficiency of vocal exploration and instruct synaptic changes in the motor pathway. We also find that learned changes in the song generated by the AFP are incorporated into the motor pathway within 1 day. Our observations support a view that basal gangliarelated circuits directly implement behavioral adaptations that minimize errors and subsequently stabilize these adaptations by training premotor cortical areas.consolidation ͉ LMAN ͉ motor learning ͉ reinforcement learning ͉ anterior forebrain pathway

Young animals engage in variable exploratory behaviors essential for the development of neural circuitry and adult motor control, yet the neural basis of these behaviors is largely unknown. Juvenile songbirds produce subsong-a succession of primitive vocalizations akin to human babbling. We found that subsong production in zebra finches does not require HVC (high vocal center), a key premotor area for singing in adult birds, but does require LMAN (lateral magnocellular nucleus of the nidopallium), a forebrain nucleus involved in learning but not in adult singing. During babbling, neurons in LMAN exhibited premotor correlations to vocal output on a fast time scale. Thus, juvenile singing is driven by a circuit distinct from that which produces the adult behavior-a separation possibly general to other developing motor systems.

Many mammalian species rely on pheromones-semiochemicals produced by other members of the same species-to communicate social status and reproductive readiness. To assess how the central nervous system integrates the complex repertoire of pheromones, we recorded from single neurons in the accessory olfactory bulb, a nucleus that processes pheromonal signals, of male mice engaged in natural behaviors. Neuronal firing was robustly modulated by physical contact with male and female conspecifics, with individual neurons activated selectively by specific combinations of the sex and strain of conspecifics. We infer that mammals encode social and reproductive information by integrating vomeronasal sensory activity specific to sex and genetic makeup.