Principal Investigator: Ted Usdin
Section on Fundamental Neuroscience
Dr. Usdin is a Senior Investigator in the Section on Fundamental Neuroscience of NIMH. He attended college at Johns Hopkins University. His graduate work in the Medical Scientist Training Program at Washington University in St. Louis with Gerald Fischbach focused on the identification of factors responsible for neuromuscular junction development. Dr. Usdin completed a residency in psychiatry at Stanford University and then in 1990 joined the NIMH Laboratory of Cell Biology. Dr. Usdin is exploring the biological role of tuberoinfundibular peptide, a new neuropeptide that his group recently discovered.
Humans and animals are subject to continually changing environmental and internal influences that affect their emotional states and behavior. Appropriate responses likely involve shifts in the activity of multiple regulatory systems. Dr. Usdin’s group is interested in the function of neuropeptide systems, which constitute a major group of neuroregulators. These regulatory systems may be part of the pathways through which drug treatments or other interventions that ameliorate the symptoms of psychiatric disease act.
Current work focuses on a particular neuropeptide system, Tuberoinfundibular Peptide of 39 residues (TIP39) and its receptor, the Parathyroid Hormone 2 (PTH2) receptor. The group identified the PTH2 receptor in a screen for novel receptors expressed within the brain, and then purified TIP39 as the endogenous ligand for this receptor. They have mapped the anatomical distribution of both the peptide and receptor in detail in rat and mouse, and confirmed that they have a similar distribution in non-human primates and humans. The peptide projects from two small discrete groups of neurons to many brain regions, and these regions contain neurons that synthesize its receptor. Several of these areas are involved in mood and anxiety-related functions, pain, stress responses and neuroendocrine function. Techniques used include pharmacology, molecular biology, functional neuroanatomy and behavior. The group has recently begun working with mice with targeted mutations in the genes encoding TIP39 and the PTH2 receptor. Current evidence supports a role for TIP39 signaling in modulation of functions that were implied by the neuroanatomical data, including stress induced anxiety-like behavior and emotional aspects of pain.
Regulation of hypothalamic signaling by tuberoinfundibular peptide of 39 residues is critical for the response to cold: a novel peptidergic mechanism of thermoregulation. Dimitrov EL, Kim YY, Usdin TB. J Neurosci. 2011 Dec 7;31(49):18166-79. doi: 10.1523/JNEUROSCI.2619-11.2011. PMID: 22159128.
Increased fear- and stress-related anxiety-like behavior in mice lacking tuberoinfundibular peptide of 39 residues. Fegley DB, Holmes A, Riordan T, Faber CA, Weiss JR, Ma S, Batkai S, Pacher P, Dobolyi A, Murphy A, Sleeman MW, Usdin TB. Genes Brain Behav. 2008 Nov;7(8):933-42. doi: 10.1111/j.1601-183X.2008.00432.x. Epub 2008 Sep 17. PMID: 18700839.
Distribution of tuberoinfundibular peptide of 39 residues and its receptor, parathyroid hormone 2 receptor, in the mouse brain. Faber CA, Dobolyi A, Sleeman M, Usdin TB. J Comp Neurol. 2007 Jun 1;502(4):563-83. PMID: 17394159.
Anatomical and physiological evidence for involvement of tuberoinfundibular peptide of 39 residues in nociception. Dobolyi A, Ueda H, Uchida H, Palkovits M, Usdin TB. Proc Natl Acad Sci U S A. 2002 Feb 5;99(3):1651-6. Epub 2002 Jan 29. PMID: 11818570.
TIP39: a new neuropeptide and PTH2-receptor agonist from hypothalamus. Usdin TB, Hoare SR, Wang T, Mezey E, Kowalak JA. Nat Neurosci. 1999 Nov;2(11):941-3. PMID: 10526330.
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