title: Contexts for dopamine specification by calcium spike activity in the CNS.
abstract: Calcium-dependent electrical activity plays a significant role in neurotransmitter specification at early stages of development. To test the hypothesis that activity-dependent differentiation depends on molecular context, we investigated the development of dopaminergic neurons in the CNS of larval Xenopus laevis. We find that different dopaminergic nuclei respond to manipulation of this early electrical activity by ion channel misexpression with different increases and decreases in numbers of dopaminergic neurons. Focusing on the ventral suprachiasmatic nucleus and the spinal cord to gain insight into these differences, we identify distinct subpopulations of neurons that express characteristic combinations of GABA and neuropeptide Y as cotransmitters and Lim1,2 and Nurr1 transcription factors. We demonstrate that the developmental state of neurons identified by their spatial location and expression of these molecular markers is correlated with characteristic spontaneous calcium spike activity. Different subpopulations of dopaminergic neurons respond differently to manipulation of this early electrical activity. Moreover, retinohypothalamic circuit activation of the ventral suprachiasmatic nucleus recruits expression of dopamine selectively in reserve pool neurons that already express GABA and neuropeptide Y. The results are consistent with the hypothesis that spontaneously active neurons expressing GABA are most susceptible to activity-dependent expression of dopamine in both the spinal cord and brain. Because loss of dopaminergic neurons plays a role in neurological disorders such as Parkinson's disease, understanding how subpopulations of neurons become dopaminergic may lead to protocols for differentiation of neurons in vitro to replace those that have been lost in vivo.
authors.affiliation: Neurobiology Section, Division of Biological Sciences and Center for Neural Circuits, Kavli Institute for Brain and Mind, University of California, San Diego, La Jolla, California 92093-0357, USA.
authors.forename: Norma A
authors.initials: NA
authors.lastname: Velázquez-Ulloa
authors.forename: Nicholas C
authors.initials: NC
authors.lastname: Spitzer
authors.forename: Davide
authors.initials: D
authors.lastname: Dulcis
mesh_terms: D000818:Animals; D020013:Calcium Signaling / Q000502:physiology*; D004298:Dopamine / Q000378:metabolism*; D018507:Gene Expression Regulation, Developmental / Q000502:physiology*; D018398:Homeodomain Proteins / Q000378:metabolism; D006801:Humans; D060850:LIM-Homeodomain Proteins; D007814:Larva; D062551:NAV1.2 Voltage-Gated Sodium Channel; D009419:Nerve Tissue Proteins; D009474:Neurons / Q000502:physiology*; D009478:Neuropeptide Y / Q000378:metabolism; D057126:Nuclear Receptor Subfamily 4, Group A, Member 2 / Q000378:metabolism; D024661:Potassium Channels, Inwardly Rectifying / Q000235:genetics / Q000378:metabolism; D051381:Rats; D015222:Sodium Channels / Q000235:genetics / Q000378:metabolism; D013116:Spinal Cord / Q000166:cytology*; D018709:Statistics, Nonparametric; D013493:Suprachiasmatic Nucleus / Q000166:cytology*; D014157:Transcription Factors; D014446:Tyrosine 3-Monooxygenase / Q000378:metabolism; D014981:Xenopus / Q000033:anatomy & histology; D029867:Xenopus Proteins / Q000378:metabolism; D005680:gamma-Aminobutyric Acid / Q000378:metabolism
chemical_list: D018398:Homeodomain Proteins; C489457:KCNJ2 protein, human; D060850:LIM-Homeodomain Proteins; C543964:Lhx1 protein, Xenopus; D062551:NAV1.2 Voltage-Gated Sodium Channel; D009419:Nerve Tissue Proteins; D009478:Neuropeptide Y; D057126:Nuclear Receptor Subfamily 4, Group A, Member 2; D024661:Potassium Channels, Inwardly Rectifying; C568251:SCN2A protein, human; C568253:Scn2A protein, rat; D015222:Sodium Channels; D014157:Transcription Factors; D029867:Xenopus Proteins; D005680:gamma-Aminobutyric Acid; D014446:Tyrosine 3-Monooxygenase; D004298:Dopamine