Section: Figures

Postdoctoral Position Available

Schahram Akbarian, Ph.D.,M.D.

Academic Role: Associate Professor

Faculty Appointment(s) In:
   Psychiatry

Other Affiliation(s):
   Brudnick Neuropsychiatric Research Institute
   Interdisciplinary Graduate Program
   Program in Neuroscience

Figure

A model whereby cAMP and NMDA receptor pathways modify chromatin in striatal neurons in response to blockade of D₂- or activation of D₁-like signaling. Blockade of D₂-like receptors removes the D₂-mediated inhibition of adenylyl cyclase (AC) activity through G_I subunits. Likewise, activation of D₁ receptors activates AC through G_o and other subunits. As a result, cAMP levels increase, thereby activating cAMP-dependent PKA (cAMP-PKA). Increased cAMP-PKA activity may then phospho-activate the NR1 subunit of the NMDA receptor, thereby activating NMDA receptor-regulated Ca²⁺ -dependent signaling pathways including L-type voltage sensitive Ca²⁺ channels (LVSCC) and Ca²⁺/calmodulin dependent kinases (CAMKs). Activation of LVSCC after inhibition of D₂-like signaling may involve additional cellular messengers other than cAMP-PKA. Furthermore, glutamatergic input from the cerebral cortex and other brain regions may activate postsynaptic NMDA receptors and LVSCC in striatal neurons. It is yet unclear which histone modifying enzymes are regulated by the cAMP-PKA and NMDA receptor and Ca²⁺-dependent pathways. However, both CAMKs and PKA have been shown to phosphorylate histone H3 and both types of kinases are known to phospho-activate CREB. Phospho-activated CREB may recruit histone acetyl-transferases, including CREB binding protein (CBP)  that in concert with other enzymes then could phospho-acetylate H3 at serine 10 and lysine 14.

Phone: 508-856-2674
E-mail: Schahram.Akbarian@umassmed.edu
Keywords: Genetic Systems, Neurobiology

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Postdoctoral Position Available A postdoctoral position is available to study in this laboratory. Contact Dr. Akbarian for additional details.