Genetic dissection of dopaminergic and noradrenergic contributions to catecholaminergic tracts in early larval zebrafish

The catecholamines dopamine and noradrenaline provide some of the major neuromodulatory systems with far‐ranging projections in the brain and spinal cord of vertebrates. However, development of these complex systems is only partially understood. Zebrafish provide an excellent model for genetic analysis of neuronal specification and axonal projections in vertebrates. Here, we analyze the ontogeny of the catecholaminergic projections in zebrafish embryos and larvae up to the fifth day of development and establish the basic scaffold of catecholaminergic connectivity. The earliest dopaminergic diencephalospinal projections do not navigate along the zebrafish primary neuron axonal scaffold but establish their own tracts at defined ventrolateral positions. By using genetic tools, we study quantitative and qualitative contributions of noradrenergic and defined dopaminergic groups to the catecholaminergic scaffold. Suppression of Tfap2a activity allows us to eliminate noradrenergic contributions, and depletion of Otp activity deletes mammalian A11‐like Otp‐dependent ventral diencephalic dopaminergic groups. This analysis reveals a predominant contribution of Otp‐dependent dopaminergic neurons to diencephalospinal as well as hypothalamic catecholaminergic tracts. In contrast, noradrenergic projections make only a minor contribution to hindbrain and spinal catecholaminergic tracts. Furthermore, we can demonstrate that, in zebrafish larvae, ascending catecholaminergic projections to the telencephalon are generated exclusively by Otp‐dependent diencephalic dopaminergic neurons as well as by hindbrain noradrenergic groups. Our data reveal the Otp‐dependent A11‐type dopaminergic neurons as the by far most prominent dopaminergic system in larval zebrafish. These findings are consistent with a hypothesis that Otp‐dependent dopaminergic neurons establish the major modulatory system for somatomotor and somatosensory circuits in larval fish. J. Comp. Neurol. 518:439–458, 2010. © 2009 Wiley‐Liss, Inc.

[1]  T. Hattori,et al.  Single thalamic dopaminergic neurons project to both the neocortex and spinal cord , 1988, Brain Research.

[2]  M. Westerfield,et al.  Secondary motoneuron axons localize DM‐GRASP on their fasciculated segments , 1999, The Journal of comparative neurology.

[3]  J. Fetcho,et al.  Relationship of tyrosine hydroxylase and serotonin immunoreactivity to sensorimotor circuitry in larval zebrafish , 2004, The Journal of comparative neurology.

[4]  R. Anadón,et al.  Experimental study of the connections of the telencephalon in the rainbow trout (Oncorhynchus mykiss). II: Dorsal area and preoptic region , 2004, The Journal of comparative neurology.

[5]  W. Smeets,et al.  Origin and development of descending catecholaminergic pathways to the spinal cord in amphibians , 2002, Brain Research Bulletin.

[6]  R. Geisler,et al.  lockjaw encodes a zebrafish tfap2a required for early neural crest development , 2003, Development.

[7]  P. Ma.  Catecholaminergic systems in the zebrafish. IV. Organization and projection pattern of dopaminergic neurons in the diencephalon , 2003, The Journal of comparative neurology.

[8]  Jan Kaslin,et al.  Comparative anatomy of the histaminergic and other aminergic systems in zebrafish (Danio rerio) , 2001, The Journal of comparative neurology.

[9]  C. Collet,et al.  Two tyrosine hydroxylase genes in teleosts. , 2005, Biochimica et biophysica acta.

[10]  K. Rommelfanger,et al.  Norepinephrine: The redheaded stepchild of Parkinson's disease. , 2007, Biochemical pharmacology.

[11]  S. Iversen,et al.  Dopamine: 50 years in perspective , 2007, Trends in Neurosciences.

[12]  L. Puelles,et al.  Prosomeric map of the lamprey forebrain based on calretinin immunocytochemistry, nissl stain, and ancillary markers , 1999, The Journal of comparative neurology.

[13]  M. Wullimann,et al.  Connections of the ventral telencephalon and tyrosine hydroxylase distribution in the zebrafish brain (Danio rerio) lead to identification of an ascending dopaminergic system in a teleost , 2002, Brain Research Bulletin.

[14]  R. Pasterkamp,et al.  Getting connected in the dopamine system , 2008, Progress in Neurobiology.

[15]  A. Björklund,et al.  Dopamine neuron systems in the brain: an update , 2007, Trends in Neurosciences.

[16]  R. Anadón,et al.  An experimental study of the connections of the telencephalon in the rainbow trout (Oncorhynchus mykiss). I: Olfactory bulb and ventral area , 2004, The Journal of comparative neurology.

[17]  J. Fetcho,et al.  Ontogeny and innervation patterns of dopaminergic, noradrenergic, and serotonergic neurons in larval zebrafish , 2004, The Journal of comparative neurology.

[18]  M. T. Shipley,et al.  Surprisingly rich projection from locus coeruleus to the olfactory bulb in the rat , 1985, Brain Research.

[19]  A. Björklund,et al.  Evidence for a major spinal cord projection from the diencephalic A11 dopamine cell group in the rat using transmitter-specific fluorescent retrograde tracing , 1979, Brain Research.

[20]  W. Smeets,et al.  Phylogeny and development of catecholamine systems in the CNS of vertebrates , 1994 .

[21]  S. Sara.  The locus coeruleus and noradrenergic modulation of cognition , 2009, Nature Reviews Neuroscience.

[22]  W. Driever,et al.  Genetic Analysis of the Roles of Hh, FGF8, and Nodal Signaling during Catecholaminergic System Development in the Zebrafish Brain , 2003, The Journal of Neuroscience.

[23]  Chi-Bin Chien,et al.  Pathfinding in a large vertebrate axon tract: isotypic interactions guide retinotectal axons at multiple choice points , 2008, Development.

[24]  M. Wullimann,et al.  Development of the catecholaminergic system in the early zebrafish brain: an immunohistochemical study. , 2002, Brain research. Developmental brain research.

[25]  Wolfgang Driever,et al.  Dopamine transporter expression distinguishes dopaminergic neurons from other catecholaminergic neurons in the developing zebrafish embryo , 2001, Mechanisms of Development.

[26]  M. Wullimann,et al.  Connections of the ventral telencephalon (subpallium) in the zebrafish (Danio rerio) , 2004, Brain Research.

[27]  S. Ryu,et al.  Orthopedia Homeodomain Protein Is Essential for Diencephalic Dopaminergic Neuron Development , 2007, Current Biology.

[28]  J. Y. Kuwada.  Development of the zebrafish nervous system: genetic analysis and manipulation , 1995, Current Opinion in Neurobiology.

[29]  P. Ma,et al.  Consistency in the number of dopaminergic paraventricular organ-accompanying neurons in the posterior tuberculum of the zebrafish brain , 2003, Brain Research.

[30]  O. Lindvall,et al.  Organization of diencephalic dopamine neurones projecting to the spinal cord in the rat , 1985, Brain Research.

[31]  E. Knapik,et al.  Noradrenergic neurons in the zebrafish hindbrain are induced by retinoic acid and require tfap2a for expression of the neurotransmitter phenotype , 2003, Development.

[32]  Keir G. Pearson,et al.  Descending command systems for the initiation of locomotion in mammals , 2008, Brain Research Reviews.

[33]  A. Frazer,et al.  Brain norepinephrine : neurobiology and therapeutics , 2007 .

[34]  A. Chitnis,et al.  Axonogenesis in the brain of zebrafish embryos , 1990, The Journal of neuroscience : the official journal of the Society for Neuroscience.

[35]  A. Graybiel,et al.  Melanized dopaminergic neurons are differentially susceptible to degeneration in Parkinson's disease , 1988, Nature.

[36]  D. O'Malley,et al.  Locomotor repertoire of the larval zebrafish: swimming, turning and prey capture. , 2000, The Journal of experimental biology.

[37]  A. Lang,et al.  Parkinson's disease. Second of two parts. , 1998, The New England journal of medicine.

[38]  C. Kimmel,et al.  Organization of hindbrain segments in the zebrafish embryo , 1990, Neuron.

[39]  P. Ma.  Catecholaminergic systems in the zebrafish. III. organization and projection pattern of medullary dopaminergic and noradrenergic neurons , 1997, The Journal of comparative neurology.

[40]  M. Wullimann,et al.  The teleostean (zebrafish) dopaminergic system ascending to the subpallium (striatum) is located in the basal diencephalon (posterior tuberculum) , 2001, Brain Research.

[41]  Stephen W. Wilson,et al.  The development of a simple scaffold of axon tracts in the brain of the embryonic zebrafish, Brachydanio rerio. , 1990, Development.

[42]  W. Schultz.  Behavioral dopamine signals , 2007, Trends in Neurosciences.

[43]  V. Sallinen,et al.  MPTP and MPP+ target specific aminergic cell populations in larval zebrafish , 2009, Journal of neurochemistry.

[44]  W. Smeets,et al.  Catecholamine systems in the brain of vertebrates: new perspectives through a comparative approach , 2000, Brain Research Reviews.

[45]  Hironobu Ito,et al.  Visual, lateral line, and auditory ascending pathways to the dorsal telencephalic area through the rostrolateral region of the lateral preglomerular nucleus in cyprinids , 2008, The Journal of comparative neurology.

[46]  P. Ma.  Catecholaminergic systems in the zebrafish. I. Number, morphology, and histochemical characteristics of neurons in the locus coeruleus , 1994, The Journal of comparative neurology.

[47]  D. Sulzer,et al.  Multiple hit hypotheses for dopamine neuron loss in Parkinson's disease , 2007, Trends in Neurosciences.

[48]  K. Fuxe,et al.  EVIDENCE FOR THE EXISTENCE OF MONOAMINE-CONTAINING NEURONS IN THE CENTRAL NERVOUS SYSTEM. I. DEMONSTRATION OF MONOAMINES IN THE CELL BODIES OF BRAIN STEM NEURONS. , 1964, Acta physiologica Scandinavica. Supplementum.

[49]  P. Ma.  Catecholaminergic systems in the zebrafish. II. Projection pathways and pattern of termination of the locus coeruleus , 1994, The Journal of comparative neurology.