Abstract

Despite recent strides in the molecular and biophysical scrutiny of ligand-gated ion channels, the developmental regulation of neuronal receptors has largely eluded analysis. Previous studies by this laboratory revealed that nicotinic acetylcholine receptors (nAChRs) expressed by central and peripheral neurons are profoundly altered during neuronal development, concurrent with synaptogenesis. In view of the complex and reciprocal nature of synapse formation, the investigators hypothesize that the induction and maturation of transmitter gated channels results from coordinate regulation by both presynaptic input and target contact.
Aim I examines the role of presynaptic input in the developmental regulation of nAChRs. The investigators will test if presynaptic activity and/or anterograde signals are required for the expression of mature nAChR channel subtypes. The analysis of input-induced changes in nAChRs combines molecular and biophysical approaches to map nAChR channel distribution and dissect nACnR subunit composition. A candidate presynaptic regulator of neuronal nAChRs has been identified. They will test for changes in nAChR expression in response to this factor and related molecules.
Aim II explores the extent of target-induced changes in nAChRs in detail, examining the mechanism(s) by which target innervation and retrograde signals control the biophysical profile, subunit composition and cellular distribution of neuronal nAChR channels.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Institute of Neurological Disorders and Stroke (NINDS)
Type
Research Project (R01)
Project #
5R01NS029071-08
Application #
2714497
Study Section
Neurological Sciences Subcommittee 1 (NLS)
Program Officer
Leblanc, Gabrielle G
Project Start
1991-01-01
Project End
1999-05-31
Budget Start
1998-06-01
Budget End
1999-05-31
Support Year
8
Fiscal Year
1998
Total Cost
Indirect Cost

  Institution

Name
Columbia University (N.Y.)
Department
Anatomy/Cell Biology
Type
Schools of Medicine
DUNS #
167204994
City
New York
State
NY
Country
United States
Zip Code
10032

  Publications

Jiang, Li; Emmetsberger, Jaime; Talmage, David A et al. (2013) Type III neuregulin 1 is required for multiple forms of excitatory synaptic plasticity of mouse cortico-amygdala circuits. J Neurosci 33:9655-66
Hancock, Melissa L; Nowakowski, Dan W; Role, Lorna W et al. (2011) Type III neuregulin 1 regulates pathfinding of sensory axons in the developing spinal cord and periphery. Development 138:4887-98
Heermann, Stephan; Schmucker, Julia; Hinz, Ursula et al. (2011) Neuregulin 1 type III/ErbB signaling is crucial for Schwann cell colonization of sympathetic axons. PLoS One 6:e28692
Canetta, Sarah E; Luca, Edlira; Pertot, Elyse et al. (2011) Type III Nrg1 back signaling enhances functional TRPV1 along sensory axons contributing to basal and inflammatory thermal pain sensation. PLoS One 6:e25108
Chen, Yachi; Hancock, Melissa L; Role, Lorna W et al. (2010) Intramembranous valine linked to schizophrenia is required for neuregulin 1 regulation of the morphological development of cortical neurons. J Neurosci 30:9199-208
Jiang, Li; Role, Lorna W (2008) Facilitation of cortico-amygdala synapses by nicotine: activity-dependent modulation of glutamatergic transmission. J Neurophysiol 99:1988-99
Hancock, Melissa L; Canetta, Sarah E; Role, Lorna W et al. (2008) Presynaptic type III neuregulin1-ErbB signaling targets {alpha}7 nicotinic acetylcholine receptors to axons. J Cell Biol 181:511-21
Zhong, Chongbo; Du, Chuang; Hancock, Melissa et al. (2008) Presynaptic type III neuregulin 1 is required for sustained enhancement of hippocampal transmission by nicotine and for axonal targeting of alpha7 nicotinic acetylcholine receptors. J Neurosci 28:9111-6
Chen, Ying-Jiun J; Johnson, Madeleine A; Lieberman, Michael D et al. (2008) Type III neuregulin-1 is required for normal sensorimotor gating, memory-related behaviors, and corticostriatal circuit components. J Neurosci 28:6872-83
Talmage, David A (2008) Mechanisms of neuregulin action. Novartis Found Symp 289:74-84;discussion 84-93

Showing the most recent 10 out of 29 publications