The main focus of the work in the Schmauss lab is on the expression and function of two members of the D2-class of dopamine receptor subtypes, named D2 and D3.  These receptors are thought to play an important role in modulating locomotor, cognitive, and motivated behavior, and they are targets for psychostimulants as well as neuroleptic drugs.

Among members of the D2-like receptor subtypes, D2 and D3 receptors share the highest degree of similarity in their primary structure and their anatomic expression overlaps substantially.  However, conventional pharmacological approaches to elucidating distinct functional properties of D2 and D3 receptors are greatly limited because of the lack of antagonists selective for each of these receptor subtypes.

In order to dissect the specific roles played by these receptors, we generated mutant mice that lack D2, D3, and D2/D3 receptors.  The figure illustrates gross phenotypic differences between wildtype (WT), D2 single mutants (D2) and D2/D3 double mutants (DM).  At present, our studies aim at investigating the distinct roles that both receptor play in:

1. the control of working memory
2. modulating spontaneous and stereotypic locomotor behavior, and
3. regulating molecular responses to psychostimulants.

Another line of investigation addresses questions relevant to mechanisms involved in modulating the post-transcriptional regulation of expression of neurotransmitter-receptor encoded pre-mRNA.  Specifically, this work focuses an alternative splicing of D3 pre-mRNA and editing of 5-HT2C pre-mRNA.  We found that RNA processing of both transcripts is altered in schizophrenia (D3) and depression (5-HT2C).

The individual projects are described below.

5-HT2C pre-mRNA Editing

Specific projects:

• Regulation of 5-HT2C pre-mRNA editing in human prefrontal cortex and mouse forebrain neocortex
  
  
• Characterization of editing-site specific alteration in depressed and schizophrenic suicide victims
  
  
• Modulation of site-specific editing frequencies in response to sustained changes in serotonergic neurotransmission
  
  
• Mechanisms underlying site-specific alterations in editing-site frequencies
  
  

Recent publications associated with these projects:

• Englander, M.T., Dulawa, Bhansali, P., and Schmauss, C. (2004).  How stress and fluoxetine modulate serotonin 2C receptor pre-mRNA editing.  J. Neurosci., in press.
  
  
• Gurevich I, Tamir H, Arango V, Dwork AJ, Mann JJ, Schmauss C.
  Altered editing of serotonin 2C receptor pre-mRNA in the prefrontal cortex of depressed suicide victims.
  Neuron 2002 Apr 25;34(3):349-56.
  Medline abstract    Full text (210K PDF file)
  
  
• Schmauss C, Howe JR.
  RNA editing of neurotransmitter receptors in the mammalian brain.
  Science's STKE 2002 May 21;2002(133):PE26.  Review.
  Medline abstract    Full text (115K PDF file)
  
  
• Gurevich I, Englander MT, Adlersberg M, Siegal NB, Schmauss C.
  Modulation of Serotonin 2C Receptor Editing by Sustained Changes in Serotonergic Neurotransmission.
  Journal of Neuroscience 2002 Dec 15;22(24):10529-32.
  Medline abstract    Full text (190K PDF file)
  
  

Current projects:

• Working memory
  
  
• Attention
  
  
• Stereotypic behavior
  
  

Recent publications associated with these projects:

• Glickstein SB, Schmauss C.
  Focused motor stereotypies do not require enhanced activation of neurons in striosomes.
  Journal of Comparative Neurology 2004 Feb 2;469(2):227-38.
  Medline abstract    Full text (445K PDF file)
  
  
• Adlersberg M, Hsiung SC, Glickstein SB, Liu KP, Tamir H, Schmauss C.
  Regulation of dopamine D-receptor activation in vivo by protein phosphatase 2B (calcineurin).
  Journal of Neurochemistry 2004 Aug;90(4):865-73.
  Medline abstract    Full text (155K PDF file)
  
  
• Glickstein SB, Desteno DA, Hof PR, Schmauss C.
  Mice Lacking Dopamine D2 and D3 Receptors Exhibit Differential Activation of Prefrontal Cortical Neurons during Tasks Requiring Attention.
  Cerebral Cortex 2004 Nov 10; [Epub ahead of print]
  Medline abstract    Full text (565K PDF file)
  
  
• Jung MY, Hof PR, Schmauss C.
  Targeted disruption of the dopamine D(2) and D(3) receptor genes leads to different alterations in the expression of striatal calbindin-D(28k).
  Neuroscience 2000;97(3):495-504.
  Medline abstract    Full text (1.4 MB PDF file)
  
  
• Schmauss C, Glickstein SB, Adlersberg M, Hsiung SC, Tamir H.
  A single dose of methamphetamine rescues the blunted dopamine D(1)-receptor activity in the neocortex of D(2)- and D(3)-receptor knockout mice.
  Annals of the New York Academy of Sciences 2002 Jun;965:21-7.
  Medline abstract  
  
  
• Schmauss C.  (2000).  Dopamine receptors:  Novel insights from biochemical and genetic studies.  The Neuroscientist 6(2): 125-136. (review)
  
  
• Glickstein SB, Schmauss C.
  Dopamine receptor functions:  lessions from knockout mice.
  Pharmacology and Therapeutics 2001 Jul;91(1):63-83.  Review.
  Medline abstract    Full text (430K PDF file)
  
  
• Glickstein SB, Hof PR, Schmauss C.
  Mice lacking dopamine D2 and D3 receptors have spatial working memory deficits.
  Journal of Neuroscience 2002 Jul 1;22(13):5619-29.
  Medline abstract    Full text (700K PDF file)