Chemical Coding of Neurotransmission

National Institute Of Mental Health

Investigators

Linked publications, trials & patents

Abstract

The eleven publications from the SMN in the past calendar year comprise seven primary reports arising from data obtained in the laboratory, and four reviews or book chapters summarizing recent progress in the neuropeptide field. In aggregate, we and our collaborators are working towards a more detailed understanding of how neuromodulators, including neuropeptides and catecholamines, collaborate at synapses within brain circuits dedicated to behavioral responses to aversive and rewarding stimuli, and stress. Most of our work involves two Gs-coupled receptors, DRD1 (for dopamine) and PAC1 (for PACAP) that signal mainly through elevation of cyclic AMP. We are building a new view of cyclic AMP signaling in which cyclic AMP activates immediate early genes for neuronal plasticity encoding experience by two separate pathways, one dedicated to fos activation and acting through the threonine-serine protein kinase A, and one dedicated to activation of the immediate early gene Egr1/Zif268 via the MAP kinase ERK, and acting through the guanine nucleotide exchanger NCS-RapGEF2. We are exploring iun particular the role of RapGEF2 in mediating hippocampal associative learning during fear conditioning; in mediating hypophagic responses to restraint stress, and in mediating dopamine-dependent cocaine-induced drug seeking behavior.