Samuel D. Gale

Organization of the songbird basal ganglia, including area X

Area X is a songbird basal ganglia nucleus that is required for vocal learning. Both Area X and its immediate surround, the medial striatum (MSt), contain cells displaying either striatal or pallidal characteristics. We used pathway‐tracing techniques to compare directly the targets of Area X and MSt with those of the lateral striatum (LSt) and globus pallidus (GP). We found that the zebra finch LSt projects to the GP, substantia nigra pars reticulata (SNr) and pars compacta (SNc), but not the thalamus. The GP is reciprocally connected with the subthalamic nucleus (STN) and projects to the SNr and motor thalamus analog, the ventral intermediate area (VIA). In contrast to the LSt, Area X and surrounding MSt project to the ventral pallidum (VP) and dorsal thalamus via pallidal‐like neurons. A dorsal strip of the MSt contains spiny neurons that project to the VP. The MSt, but not Area X, projects to the ventral tegmental area (VTA) and SNc, but neither MSt nor Area X projects to the SNr. Largely distinct populations of SNc and VTA dopaminergic neurons innervate Area X and surrounding the MSt. Finally, we provide evidence consistent with an indirect pathway from the cerebellum to the basal ganglia, including Area X. Area X projections thus differ from those of the GP and LSt, but are similar to those of the MSt. These data clarify the relationships among different portions of the oscine basal ganglia as well as among the basal ganglia of birds and mammals. J. Comp. Neurol. 508:840–866, 2008.

A novel basal ganglia pathway forms a loop linking a vocal learning circuit with its dopaminergic input

Dopamine has been implicated in mediating contextual modulation of motor behaviors and learning in many species. In songbirds, dopamine may act on the basal ganglia nucleus Area X to influence the neural activity that contributes to vocal learning and contextual changes in song variability. Neurons in midbrain dopamine centers, the substantia nigra pars compacta (SNc) and ventral tegmental area (VTA), densely innervate Area X and show singing‐related changes in firing rate. In addition, dopamine levels in Area X change during singing. It is unknown, however, how song‐related information could reach dopaminergic neurons. Here we report an anatomical pathway that could provide song‐related information to the SNc and VTA. By using injections of bidirectionally transported fluorescent tracers in adult male zebra finches, we show that Area X and other song control nuclei do not project directly to the SNc or VTA. Instead, we describe an indirect pathway from Area X to midbrain dopaminergic neurons via a connection in the ventral pallidum (VP). Specifically, Area X projects to the VP via axon collaterals of Area X output neurons that also project to the thalamus. Dual injections revealed that the area of VP receiving input from Area X projects to the SNc and VTA. Furthermore, VP terminals in the SNc and VTA overlap with cells that project back to Area X. A portion of the arcopallium also projects to the SNc and VTA and could carry auditory information. These data demonstrate an anatomical loop through which Area X activity could influence its dopaminergic input. J. Comp. Neurol. 508:824–839, 2008.

A Basal Ganglia Pathway Drives Selective Auditory Responses in Songbird Dopaminergic Neurons via Disinhibition

Dopaminergic neurons in mammals respond to rewards and reward-predicting cues, and are thought to play an important role in learning actions or sensory cues that lead to reward. The anatomical sources of input that drive or modulate such responses are not well understood; these ultimately define the range of behavior to which dopaminergic neurons contribute. Primary rewards are not the immediate objective of all goal-directed behavior. For example, a goal of vocal learning is to imitate vocal-communication signals. Here, we demonstrate activation of dopaminergic neurons in songbirds driven by a basal ganglia region required for vocal learning, area X. Dopaminergic neurons in anesthetized zebra finches respond more strongly to the birds own song (BOS) than to other sounds, and area X is critical for these responses. Direct pharmacological modulation of area X output, in the absence of auditory stimulation, is sufficient to bidirectionally modulate the firing rate of dopaminergic neurons. The only known pathway from song control regions to dopaminergic neurons involves a projection from area X to the ventral pallidum (VP), which in turn projects to dopaminergic regions. We show that VP neurons are spontaneously active and inhibited preferentially by BOS, suggesting that area X disinhibits dopaminergic neurons by inhibiting VP. Supporting this model, auditory-response latencies are shorter in area X than VP, and shorter in VP than dopaminergic neurons. Thus, dopaminergic neurons can be disinhibited selectively by complex sensory stimuli via input from the basal ganglia. The functional pathway we identify may allow dopaminergic neurons to contribute to vocal learning.

A major role for zygotic hunchback in patterning the Nasonia embryo

Developmental genetic analysis has shown that embryos of the parasitoid wasp Nasonia vitripennis depend more on zygotic gene products to direct axial patterning than do Drosophila embryos. In Drosophila, anterior axial patterning is largely established by bicoid, a rapidly evolving maternal-effect gene, working with hunchback, which is expressed both maternally and zygotically. Here, we focus on a comparative analysis of Nasonia hunchback function and expression. We find that a lesion in Nasonia hunchback is responsible for the severe zygotic headless mutant phenotype, in which most head structures and the thorax are deleted, as are the three most posterior abdominal segments. This defines a major role for zygotic Nasonia hunchback in anterior patterning, more extensive than the functions described for hunchback in Drosophila or Tribolium. Despite the major zygotic role of Nasonia hunchback, we find that it is strongly expressed maternally, as well as zygotically. Nasonia Hunchback embryonic expression appears to be generally conserved; however, the mRNA expression differs from that of Drosophila hunchback in the early blastoderm. We also find that the maternal hunchback message decays at an earlier developmental stage in Nasonia than in Drosophila, which could reduce the relative influence of maternal products in Nasonia embryos. Finally, we extend the comparisons of Nasonia and Drosophila hunchback mutant phenotypes, and propose that the more severe Nasonia hunchback mutant phenotype may be a consequence of differences in functionally overlapping regulatory circuitry.

Anatomy of a songbird basal ganglia circuit essential for vocal learning and plasticity.

Vocal learning in songbirds requires an anatomically discrete and functionally dedicated circuit called the anterior forebrain pathway (AFP). The AFP is homologous to cortico-basal ganglia-thalamo-cortical loops in mammals. The basal ganglia portion of this pathway, Area X, shares many features characteristic of the mammalian striatum and pallidum, including cell types and connectivity. The AFP also deviates from mammalian basal ganglia circuits in fundamental ways. In addition, the microcircuitry, role of neuromodulators, and function of Area X are still unclear. Elucidating the mechanisms by which both mammalian-like and unique features of the AFP contribute to vocal learning may help lead to a broad understanding of the sensorimotor functions of basal ganglia circuits.

Postsynaptic neural activity regulates neuronal addition in the adult avian song control system.

Significance Neural activity in the adult brain plays a key role in mediating experience-dependent neural plasticity. We show that inhibiting electrical activity in the song nucleus, robust nucleus of the arcopallium, in adult bird brain decreases the number of new projection neurons added to the afferent nucleus HVC. Our results are consistent with the general principle of activity-based target selection of newborn neurons during nervous system development and support the idea that developmental and adult plasticity exploit similar mechanisms. Understanding mechanisms influencing the incorporation of new neurons into established neural circuits in adult brains is critical for our basic understanding of neural plasticity and for exploiting the clinical potential of neuronal replacement to repair damage associated with injury and neurodegenerative diseases. A striking feature of the nervous system is that it shows extensive plasticity of structure and function that allows animals to adjust to changes in their environment. Neural activity plays a key role in mediating experience-dependent neural plasticity and, thus, creates a link between the external environment, the nervous system, and behavior. One dramatic example of neural plasticity is ongoing neurogenesis in the adult brain. The role of neural activity in modulating neuronal addition, however, has not been well studied at the level of neural circuits. The avian song control system allows us to investigate how activity influences neuronal addition to a neural circuit that regulates song, a learned sensorimotor social behavior. In adult white-crowned sparrows, new neurons are added continually to the song nucleus HVC (proper name) and project their axons to its target nucleus, the robust nucleus of the arcopallium (RA). We report here that electrical activity in RA regulates neuronal addition to HVC. Decreasing neural activity in RA by intracerebral infusion of the GABAA receptor agonist muscimol decreased the number of new HVC neurons by 56%. Our results suggest that postsynaptic electrical activity influences the addition of new neurons into a functional neural circuit in adult birds.

Distinct cell types in the superficial superior colliculus project to the dorsal lateral geniculate and lateral posterior thalamic nuclei

The superficial layers of the superior colliculus (sSC) receive retinal input and project to thalamic regions, the dorsal lateral geniculate (dLGN) and lateral posterior (LP; or pulvinar) nuclei, that convey visual information to cortex. A critical step toward understanding the functional impact of sSC neurons on these parallel thalamo-cortical pathways is determining whether different classes of sSC neurons, which are known to respond to different features of visual stimuli, innervate overlapping or distinct thalamic targets. Here, we identified a transgenic mouse line that labels sSC neurons that project to dLGN but not LP. We utilized selective expression of fluorophores and channelrhodopsin in this and previously characterized mouse lines to demonstrate that distinct cell types give rise to sSC projections to dLGN and LP. We further show that the glutamatergic sSC cell type that projects to dLGN also provides input to the sSC cell type that projects to LP. These results clarify the cellular origin of parallel sSC-thalamo-cortical pathways and reveal an interaction between these pathways via local connections within the sSC. NEW & NOTEWORTHY The superficial layers of the superior colliculus (sSC) project to two visual thalamic targets: the dorsal lateral geniculate (dLGN) and lateral posterior (LP) nuclei. We show that distinct excitatory sSC cell types give rise to these projections; stellate cells project to dLGN and wide-field (WF) cells project to LP. Moreover, these pathways interact via a connection within the sSC from stellate to WF cells.