@article {49294, title = {Distinct cell types in the superficial superior colliculus project to the dorsal lateral geniculate and lateral posterior thalamic nuclei.}, journal = {Journal of Neurophysiology}, volume = {120}, year = {2018}, month = {2018 Jun 13}, pages = {1286-92}, abstract = {

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 towards 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.

}, issn = {1522-1598}, doi = {10.1152/jn.00248.2018}, author = {Gale, Samuel D and Murphy, Gabe J} } @article {48468, title = {Active dendritic properties and local inhibitory input enable selectivity for object motion in mouse superior colliculus neurons.}, journal = {The Journal of Neuroscience : the Official Journal of the Society for Neuroscience}, volume = {36}, year = {2016}, month = {2016 Aug 31}, pages = {9111-23}, abstract = {

UNLABELLED: Neurons respond to specific features of sensory stimuli. In the visual system, for example, some neurons respond to motion of small but not large objects, whereas other neurons prefer motion of the entire visual field. Separate neurons respond equally to local and global motion but selectively to additional features of visual stimuli. How and where does response selectivity emerge? Here, we show that wide-field (WF) cells in retino-recipient layers of the mouse superior colliculus (SC) respond selectively to small moving objects. Moreover, we identify two mechanisms that contribute to this selectivity. First, we show that input restricted to a small portion of the broad dendritic arbor of WF cells is sufficient to trigger dendritic spikes that reliably propagate to the soma/axon. In vivo whole-cell recordings reveal that nearly every action potential evoked by visual stimuli has characteristics of spikes initiated in dendrites. Second, inhibitory input from a different class of SC neuron, horizontal cells, constrains the range of stimuli to which WF cells respond. Horizontal cells respond preferentially to the sudden appearance or rapid movement of large stimuli. Optogenetic reduction of their activity reduces movement selectivity and broadens size tuning in WF cells by increasing the relative strength of responses to stimuli that appear suddenly or cover a large region of space. Therefore, strongly propagating dendritic spikes enable small stimuli to drive spike output in WF cells and local inhibition helps restrict responses to stimuli that are both small and moving.

SIGNIFICANCE STATEMENT: How do neurons respond selectively to some sensory stimuli but not others? In the visual system, a particularly relevant stimulus feature is object motion, which often reveals other animals. Here, we show how specific cells in the superior colliculus, one synapse downstream of the retina, respond selectively to object motion. These wide-field (WF) cells respond strongly to small objects that move slowly anywhere through a large region of space, but not to stationary objects or full-field motion. Action potential initiation in dendrites enables small stimuli to trigger visual responses and inhibitory input from cells that prefer large, suddenly appearing, or quickly moving stimuli restricts responses of WF cells to objects that are small and moving.

}, issn = {1529-2401}, doi = {10.1523/JNEUROSCI.0645-16.2016}, author = {Gale, Samuel D and Murphy, Gabe J} } @article {45686, title = {Distinct representation and distribution of visual information by specific cell types in mouse superficial superior colliculus.}, journal = {The Journal of Neuroscience}, volume = {34}, year = {2014}, month = {2014 Oct 1}, pages = {13458-71}, abstract = {

The superficial superior colliculus (sSC) occupies a critical node in the mammalian visual system; it is one of two major retinorecipient areas, receives visual cortical input, and innervates visual thalamocortical circuits. Nonetheless, the contribution of sSC neurons to downstream neural activity and visually guided behavior is unknown and frequently neglected. Here we identified the visual stimuli to which specific classes of sSC neurons respond, the downstream regions they target, and transgenic mice enabling class-specific manipulations. One class responds to small, slowly moving stimuli and projects exclusively to lateral posterior thalamus; another, comprising GABAergic neurons, responds to the sudden appearance or rapid movement of large stimuli and projects to multiple areas, including the lateral geniculate nucleus. A third class exhibits direction-selective responses and targets deeper SC layers. Together, our results show how specific sSC neurons represent and distribute diverse information and enable direct tests of their functional role.

}, issn = {1529-2401}, doi = {10.1523/JNEUROSCI.2768-14.2014}, author = {Gale, Samuel D and Murphy, Gabe J} } @article {1415, title = {Anatomy of a songbird basal ganglia circuit essential for vocal learning and plasticity.}, journal = {Journal of Chemical Neuroanatomy}, volume = {39}, year = {2010}, month = {2010 Mar}, pages = {124-31}, abstract = {

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.

}, keywords = {Animal, Animals, Basal Ganglia, Birds, Brain, Catecholamines, Globus Pallidus, Learning, Neural Pathways, Neuronal Plasticity, Neurons, Thalamus, Vocalization}, issn = {1873-6300}, doi = {10.1016/j.jchemneu.2009.07.003}, author = {Gale, Samuel D and Perkel, David J} } @article {1416, title = {A basal ganglia pathway drives selective auditory responses in songbird dopaminergic neurons via disinhibition.}, journal = {The Journal of Neuroscience: The Official Journal of the Society for Neuroscience}, volume = {30}, year = {2010}, month = {2010 Jan 20}, pages = {1027-37}, abstract = {

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 bird{\textquoteright}s 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.

}, keywords = {Acoustic Stimulation, Action Potentials, Animal, Animals, Auditory Pathways, Basal Ganglia, Discrimination (Psychology), Dopamine, Electric Stimulation, Excitatory Amino Acid Antagonists, Finches, gamma-Aminobutyric Acid, Male, Neural Inhibition, Neurons, Reaction Time, Tyrosine 3-Monooxygenase, Ventral Tegmental Area, Vocalization}, issn = {1529-2401}, doi = {10.1523/JNEUROSCI.3585-09.2010}, author = {Gale, Samuel D and Perkel, David J} } @article {1413, title = {A novel basal ganglia pathway forms a loop linking a vocal learning circuit with its dopaminergic input.}, journal = {The Journal of Comparative Neurology}, volume = {508}, year = {2008}, month = {2008 Jun 10}, pages = {824-39}, abstract = {

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.

}, keywords = {Animal, Animals, Basal Ganglia, Dopamine, Finches, Learning, Male, Nerve Net, Neural Pathways, Vocalization}, issn = {1096-9861}, doi = {10.1002/cne.21700}, author = {Gale, Samuel D and Person, Abigail L and Perkel, David J} } @article {1414, title = {Organization of the songbird basal ganglia, including area X.}, journal = {The Journal of Comparative Neurology}, volume = {508}, year = {2008}, month = {2008 Jun 10}, pages = {840-66}, abstract = {

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.

}, keywords = {Animals, Basal Ganglia, Finches, Male, Neural Pathways, Songbirds}, issn = {1096-9861}, doi = {10.1002/cne.21699}, author = {Person, Abigail L and Gale, Samuel D and Farries, Michael A and Perkel, David J} } @article {1410, title = {Cre recombinase-mediated restoration of nigrostriatal dopamine in dopamine-deficient mice reverses hypophagia and bradykinesia.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {103}, year = {2006}, month = {2006 Jun 6}, pages = {8858-63}, abstract = {

A line of dopamine-deficient (DD) mice was generated to allow selective restoration of normal dopamine signaling to specific brain regions. These DD floxed stop (DDfs) mice have a nonfunctional Tyrosine hydroxylase (Th) gene because of insertion of a NeoR gene flanked by lox P sites targeted to the first intron of the Th gene. DDfs mice have trace brain dopamine content, severe hypoactivity, and aphagia, and they die without intervention. However, they can be maintained by daily treatment with l-3,4-dihydroxyphenylalanine (L-dopa). Injection of a canine adenovirus (CAV-2) engineered to express Cre recombinase into the central caudate putamen restores normal Th gene expression to the midbrain dopamine neurons that project there because CAV-2 efficiently transduces axon terminals and is retrogradely transported to neuronal cell bodies. Bilateral injection of Cre recombinase into the central caudate putamen restores feeding and normalizes locomotion in DDfs mice. Analysis of feeding behavior by using lickometer cages revealed that virally rescued DDfs mice are hyperphagic and have modified meal structures compared with control mice. The virally rescued DDfs mice are also hyperactive at night, have reduced motor coordination, and are thigmotactic compared with controls. These results highlight the critical role for dopamine signaling in the dorsal striatum for most dopamine-dependent behaviors but suggest that dopamine signaling in other brain regions is important to fine-tune these behaviors. This approach offers numerous advantages compared with previous models aimed at examining dopamine signaling in discrete dopaminergic circuits.

}, keywords = {Adenoviridae, Animals, Brain, Dogs, Dopamine, Eating Disorders, Feeding Behavior, Gene Therapy, Hypokinesia, Inbred C57BL, Integrases, Mice, Motor Activity, Tyrosine 3-Monooxygenase, Viral Proteins}, issn = {0027-8424}, doi = {10.1073/pnas.0603081103}, author = {Hnasko, Thomas S and Perez, Francisco A and Scouras, Alex D and Stoll, Elizabeth A and Gale, Samuel D and Luquet, Serge and Phillips, Paul E M and Kremer, Eric J and Palmiter, Richard D} } @article {1407, title = {Physiological properties of zebra finch ventral tegmental area and substantia nigra pars compacta neurons.}, journal = {Journal of Neurophysiology}, volume = {96}, year = {2006}, month = {2006 Nov}, pages = {2295-306}, abstract = {

The neurotransmitter dopamine plays important roles in motor control, learning, and motivation in mammals and probably other animals as well. The strong dopaminergic projection to striatal regions and more moderate dopaminergic projections to other regions of the telencephalon predominantly arise from midbrain dopaminergic neurons in the substantia nigra pars compacta (SNc) and ventral tegmental area (VTA). Homologous dopaminergic cell groups in songbirds project anatomically in a manner that may allow dopamine to influence song learning or song production. The electrophysiological properties of SNc and VTA neurons have not previously been studied in birds. Here we used whole cell recordings in brain slices in combination with tyrosine-hydroxylase immunolabeling as a marker of dopaminergic neurons to determine electrophysiological and pharmacological properties of dopaminergic and nondopaminergic neurons in the zebra finch SNc and VTA. Our results show that zebra finch dopaminergic neurons possess physiological properties very similar to those of mammalian dopaminergic neurons, including broad action potentials, calcium- and apamin-sensitive membrane-potential oscillations underlying pacemaker firing, powerful spike-frequency adaptation, and autoinhibition via D2 dopamine receptors. Moreover, the zebra finch SNc and VTA also contain nondopaminergic neurons with similarities (fast-firing, inhibition by the mu-opioid receptor agonist [d-Ala(2), N-Me-Phe(4), Gly-ol(5)]-enkephalin (DAMGO)) and differences (strong h-current that contributes to spontaneous firing) compared with GABAergic neurons in the mammalian SNc and VTA. Our results provide insight into the intrinsic membrane properties that regulate the activity of dopaminergic neurons in songbirds and add to strong evidence for anatomical, physiological, and functional similarities between the dopaminergic systems of mammals and birds.

}, keywords = {Action Potentials, Ala(2)-MePhe(4)-Gly(5)-, Animals, Cholera Toxin, Dopamine D2, Electrophysiology, Enkephalin, Finches, Lysine, Male, mu, Neurons, Opioid, Patch-Clamp Techniques, Quinpirole, Receptors, Substantia Nigra, Tetrodotoxin, Tyrosine 3-Monooxygenase, Ventral Tegmental Area}, issn = {0022-3077}, doi = {10.1152/jn.01040.2005}, author = {Gale, Samuel D and Perkel, David J} } @article {1409, title = {A major role for zygotic hunchback in patterning the Nasonia embryo.}, journal = {Development }, volume = {132}, year = {2005}, month = {2005 Aug}, pages = {3705-15}, abstract = {

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.

}, keywords = {Animals, Base Sequence, Body Patterning, Developmental, DNA-Binding Proteins, Drosophila Proteins, Gene Expression Regulation, Genetic Linkage, HMGB Proteins, In Situ Hybridization, Insect Proteins, Messenger, Molecular Sequence Data, RNA, Sequence Alignment, Stored, TCF Transcription Factors, Transcription Factor 7-Like 1 Protein, Transcription Factors, Wasps}, issn = {0950-1991}, doi = {10.1242/dev.01939}, author = {Pultz, Mary Anne and Westendorf, Lori and Gale, Samuel D and Hawkins, Kyle and Lynch, Jeremy and Pitt, Jason N and Reeves, Nick L and Yao, Jennifer C Y and Small, Stephen and Desplan, Claude and Leaf, David S} } @article {1405, title = {Properties of dopamine release and uptake in the songbird basal ganglia.}, journal = {Journal of Neurophysiology}, volume = {93}, year = {2005}, month = {2005 Apr}, pages = {1871-9}, abstract = {

Vocal learning in songbirds requires a basal ganglia circuit termed the anterior forebrain pathway (AFP). The AFP is not required for song production, and its role in song learning is not well understood. Like the mammalian striatum, the striatal component of the AFP, Area X, receives dense dopaminergic innervation from the midbrain. Since dopamine (DA) clearly plays a crucial role in basal ganglia-mediated motor control and learning in mammals, it seems likely that DA signaling contributes importantly to the functions of Area X as well. In this study, we used voltammetric methods to detect subsecond changes in extracellular DA concentration to gain better understanding of the properties and regulation of DA release and uptake in Area X. We electrically stimulated Ca(2+)- and action potential-dependent release of an electroactive substance in Area X brain slices and identified the substance as DA by the voltammetric waveform, electrode selectivity, and neurochemical and pharmacological evidence. As in the mammalian striatum, DA release in Area X is depressed by autoinhibition, and the lifetime of extracellular DA is strongly constrained by monoamine transporters. These results add to the known physiological similarities of the mammalian and songbird striatum and support further use of voltammetry in songbirds to investigate the role of basal ganglia DA in motor learning.

}, keywords = {Animals, Basal Ganglia, Dopamine, Male, Neural Pathways, Presynaptic, Receptors, Songbirds}, issn = {0022-3077}, doi = {10.1152/jn.01053.2004}, author = {Gale, Samuel D and Perkel, David J} }