Molecular Genetics

<body topmargin=0 leftmargin=0 marginheight=0 marginwidth=0> <table cellpadding=0 cellspacing=0 border=0 height="100%"><tr> <td valign="top" width=12.5% BGCOLOR="#FFFFFF" TEXT="#080000"> <bR> <bR> <bR> </td> <td valign="top" width="100%" style=" border-top: 26px solid #FFFFFF; border-left: 63px solid #FFFFFF;border-right: 63px solid #FFFFFF;" BGCOLOR="#FFFFFF" TEXT="#080000"> <bR> <div> <TABLE BORDER="1" CELLPADDING="0" CELLSPACING="0" WIDTH="785" BORDERCOLORLIGHT="#808080" BORDERCOLORDARK="#FFFFFF" FRAME="BOX" RULES="ALL" HSPACE="0" VSPACE="0" > <tR> <tD VALIGN=TOP BGCOLOR=#DDDDDD HEIGHT= 76 ><NOBR><div> <A HREF="index.htm" TARGET="_top" TITLE="Silvalab"><B><IMG SRC="14860c470.png" border=0 width="780" height="71" ALIGN="BOTTOM" HSPACE="0" VSPACE="0"></B></A></div> </NOBR></tD> </tR> <tR> <tD VALIGN=TOP BGCOLOR=#BBBBBB HEIGHT= 30 ><NOBR><div> <B> </B><A HREF="projects.htm" TARGET="_top" TITLE="Projects "><B><IMG SRC="147e61190.png" border=0 width="97" height="25" ALIGN="BOTTOM" HSPACE="0" VSPACE="0"></B></A><A HREF="approaches.htm" TARGET="_top" TITLE="Approaches"><B><IMG SRC="147f61190.png" border=0 width="97" height="25" ALIGN="BOTTOM" HSPACE="0" VSPACE="0"></B></A><A HREF="publications.htm" TARGET="_top" TITLE="Publications"><B><IMG SRC="148061190.png" border=0 width="97" height="25" ALIGN="BOTTOM" HSPACE="0" VSPACE="0"></B></A><A HREF="personnel.htm" TARGET="_top" TITLE="Lab Members"><B><IMG SRC="148161190.png" border=0 width="97" height="25" ALIGN="BOTTOM" HSPACE="0" VSPACE="0"></B></A><A HREF="alcino.htm" TARGET="_top" TITLE="Alcino J. Silva"><B><IMG SRC="148261190.png" border=0 width="97" height="25" ALIGN="BOTTOM" HSPACE="0" VSPACE="0"></B></A><A HREF="funding.htm" TARGET="_top" TITLE="Awards"><B><IMG SRC="148361190.png" border=0 width="97" height="25" ALIGN="BOTTOM" HSPACE="0" VSPACE="0"></B></A><A HREF="positions.htm" TARGET="_top" TITLE="Open Positions"><B><IMG SRC="148461190.png" border=0 width="97" height="25" ALIGN="BOTTOM" HSPACE="0" VSPACE="0"></B></A><A HREF="aboutus.htm" TARGET="_top" TITLE="aboutus"><B><IMG SRC="148561190.png" border=0 width="97" height="25" ALIGN="BOTTOM" HSPACE="0" VSPACE="0"></B></A></div> </NOBR></tD> </tR> <tR> <tD VALIGN=TOP BGCOLOR=#6666CC HEIGHT= 20 WIDTH="781"><div>        <A HREF="index.htm" TARGET="_top" TITLE="Silvalab"><B>Home</B></A></div> </tD> </tR> </TABLE></div> <div> <TABLE BORDER="0" CELLPADDING="4" CELLSPACING="10" WIDTH="748" BORDERCOLORLIGHT="#330000" BORDERCOLORDARK="#FFFFFF" FRAME="BOX" RULES="ALL" HSPACE="0" VSPACE="0" > <tR> <tD VALIGN=TOP HEIGHT= 52 WIDTH="720"><div> <B>Molecular Genetics</B><B>   ·   </B><A HREF="approaches69.htm" TARGET="_top" TITLE="PRISM">PRISM</A><B>   ·   </B><A HREF="electrophysiology.htm" TARGET="_top" TITLE="Electrophysiology">Electrophysiology</A><B>   ·   </B><A HREF="approaches67.htm" TARGET="_top" TITLE="Neuroanatomy">Neuroanatomy</A><B>   ·   </B><A HREF="approaches339.htm" TARGET="_top" TITLE="in vivo Imaging">in vivo Imaging</A><B>   ·   </B><A HREF="approaches68.htm" TARGET="_top" TITLE="Single Unit Recordings">Single Unit Recordings</A><B>   ·   </B><A HREF="behavior.htm" TARGET="_top" TITLE="Behavioral Analyses">Behavioral Analyses</A><B>   ·   </B><A HREF="mice_to_men.htm" TARGET="_top" TITLE="Bridging Mice and Men">Bridging Mice and Men</A></div> </tD> </tR> <tR> <tD VALIGN=TOP ROWSPAN=2 HEIGHT= 199 WIDTH="720"><div> <IMG SRC="1376cb70.png" border=0 width="364" height="183" ALIGN="BOTTOM" HSPACE="0" VSPACE="0"></div> <div> C<FONT SIZE="2" COLOR="#555555" FACE="Calibri" >A1 and Dentate Gyrus Cre Lines</FONT></div> <div> Molecular Genetics</div> <bR> <div> Our laboratory generates mice with specific genetic changes to test the involvement of certain molecular components in learning and memory.  We also use other molecular strategies to manipulate brain function, including viral vectors and pharmacological manipulations. For example, we have derived genetic mutations that affect learning in mice, and others that only affect memory. We are using information from these studies to develop treatments for <A HREF="ld.htm" TARGET="_top" TITLE="Learning disabilities">genetic disorders</A> that affect learning and memory in humans. For example, we are currently testing treatments of <A HREF="nf1.htm" TARGET="_top" TITLE="Neurofibromatosis Type I"> Neurofibromatosis type I</A> and <A HREF="tsc.htm" TARGET="_top" TITLE="TSC">TSC</A> that derived from our mouse studies of this disorder.</div> <bR> </tD> </tR> <tR> </tR> <tR> <tD VALIGN=TOP HEIGHT= 187 WIDTH="720"><div> Inducible, and region restricted mutations</div> <bR> <div> <B>One of the goals of our molecular genetic studies is to develop strategies that allow us to manipulate gene function at specific times and in defined brain regions.  For example, we have recently used a strategy that takes advantage of the ligand binding domain of the estrogen receptor.  This strategy allows us to regulate the function of a transgenic mutant transcription factor (</B><A HREF="creb.htm" TARGET="_top" TITLE="CREB And Memory"><B>CREB)</B></A><B>. We were able to fully induce the function of this mutant protein in 6 hr. and to completely shut it down in  24 hr. The pictures above show Cre-mediated gene deletions directed specifically to the dentate gyrus or the CA1 region of the hippocampus. These regional-specific genetic deletions will be critical to dissect the function of hippocampal networks</B></div> </tD> </tR> <tR> <tD VALIGN=TOP HEIGHT= 203 ><NOBR><div> <TABLE BORDER="0" CELLPADDING="2" CELLSPACING="1" WIDTH="526" BORDERCOLORLIGHT="#C0C0C0" BORDERCOLORDARK="#808080" FRAME="BOX" RULES="ALL" HSPACE="0" VSPACE="0" > <tR> <tD VALIGN=TOP HEIGHT= 172 WIDTH="520"><div> Viral Vectors</div> <bR> <div> <B>With viral vectors (in collaboration with </B><A HREF="http://www.researchmatters.harvard.edu/people.php?people_id=776" TARGET="_top" TITLE="http://www.researchmatters.harvard.edu/p"><B>Rachael Neve</B></A><B>), we have been able to introduce exogenous CREB into the amygdala (a brain structure key to emotions) of adult CREB mutant mice. After restoring CREB in the amygdala, the mutant mice regained the ability to form certain types of emotional memory, indicating that CREB in the amygdala is required for the establishment of emotional memories. With viral vectors, we also showed that CREB can determine where memories are stored in networks (click here for the PDF)</B></div> </tD> </tR> </TABLE></div> <bR> </NOBR></tD> </tR> <tR> <tD VALIGN=TOP HEIGHT= 76 WIDTH="720"><bR> <bR> <div> <B>Molecular Genetics</B><B>   ·   </B><A HREF="approaches69.htm" TARGET="_top" TITLE="PRISM">PRISM</A><B>   ·   </B><A HREF="electrophysiology.htm" TARGET="_top" TITLE="Electrophysiology">Electrophysiology</A><B>   ·   </B><A HREF="approaches67.htm" TARGET="_top" TITLE="Neuroanatomy">Neuroanatomy</A><B>   ·   </B><A HREF="approaches339.htm" TARGET="_top" TITLE="in vivo Imaging">in vivo Imaging</A><B>   ·   </B><A HREF="approaches68.htm" TARGET="_top" TITLE="Single Unit Recordings">Single Unit Recordings</A><B>   ·   </B><A HREF="behavior.htm" TARGET="_top" TITLE="Behavioral Analyses">Behavioral Analyses</A><B>   ·   </B><A HREF="mice_to_men.htm" TARGET="_top" TITLE="Bridging Mice and Men">Bridging Mice and Men</A></div> </tD> </tR> </TABLE></div> <bR> <bR> <bR> <bR> <bR> </td> </tr></table></body>