Electrostimulation to reduce synaptic scaling driven progression of Alzheimers (Rowan et al. 2014)

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Accession:154096
"... As cells die and synapses lose their drive, remaining cells suffer an initial decrease in activity. Neuronal homeostatic synaptic scaling then provides a feedback mechanism to restore activity. ... The scaling mechanism increases the firing rates of remaining cells in the network to compensate for decreases in network activity. However, this effect can itself become a pathology, ... Here, we present a mechanistic explanation of how directed brain stimulation might be expected to slow AD progression based on computational simulations in a 470-neuron biomimetic model of a neocortical column. ... "
Reference:
1 . Rowan MS, Neymotin SA, Lytton WW (2014) Electrostimulation to reduce synaptic scaling driven progression of Alzheimer's disease. Front Comput Neurosci 8:39 [PubMed]
Model Information (Click on a link to find other models with that property)
Model Type: Realistic Network;
Brain Region(s)/Organism: Neocortex;
Cell Type(s): Neocortex V1 L6 pyramidal corticothalamic cell; Neocortex V1 L2/6 pyramidal intratelencephalic cell; Neocortex V1 interneuron basket PV cell; Neocortex fast spiking (FS) interneuron; Neocortex spiny stellate cell; Neocortex spiking regular (RS) neuron; Neocortex spiking low threshold (LTS) neuron;
Channel(s):
Gap Junctions:
Receptor(s): GabaA; AMPA; NMDA;
Gene(s):
Transmitter(s): Gaba; Glutamate;
Simulation Environment: NEURON; Python;
Model Concept(s): Long-term Synaptic Plasticity; Aging/Alzheimer`s; Deep brain stimulation; Homeostasis;
Implementer(s): Lytton, William [billl at neurosim.downstate.edu]; Neymotin, Sam [samn at neurosim.downstate.edu]; Rowan, Mark [m.s.rowan at cs.bham.ac.uk];
Search NeuronDB for information about:  Neocortex V1 L6 pyramidal corticothalamic cell; Neocortex V1 L2/6 pyramidal intratelencephalic cell; Neocortex V1 interneuron basket PV cell; GabaA; AMPA; NMDA; Gaba; Glutamate;
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RowanEtAl2014
mod
infot.mod *
intf6.mod *
intfsw.mod *
misc.mod *
myfft.mod *
nstim.mod *
place.mod *
sampen.mod *
staley.mod *
stats.mod *
tsa.mod *
updown.mod *
vecst.mod *
bpf.h *
misc.h *
mkmod *
parameters.multi *
                            
#!/usr/bin/perl
# $Id: mkmod,v 1.76 2011/08/17 14:28:56 billl Exp $
# mkmod is the updated version of makemod using nmodl INCLUDE statements
# Most mechanisms can be inserted by using a sparse declaration that utilizes
# INCLUDE.  
#________________________________________________________________
# E.G.
# NEURON {
#   SUFFIX NAME
# }
#
# PARAMETER {
#   param1 = 15
#   ...
# }
#
# INCLUDE "body.inc"
#________________________________________________________________
# 
# mod files that are to simply be compiled as is should use the
# DEFAULT key word 
# 

$file = "parameters.multi";  # default name
$filecreate = 1;
$nsp = $condor = 0;
$nrnmodlflag = 1;
$uname = $ENV{"CPU"};
$neuronhome = $ENV{"NEURON"};

$nrnmodl = "nrnivmodl";
$loadflags="";

if (-f $ARGV[0]) { 
    $file = shift; 
    $nsp = 1;  # new special
    $oldsp="$uname/special"; $newsp=$file; $newsp =~ s/([^.]+).multi/\1/;
    $oldlib="$uname/.libs/libnrnmech.so.0.0.0"; 
    $newlib = "$uname/.libs/libnrnmech.".$newsp;
    $newsp = "$uname/special.".$newsp; 
    if (-f $oldsp) {
      rename($oldsp,"spe.SAV");
      rename($oldlib,"lib.SAV");
    } else { die "$oldsp not found\n"; }
    print "Using $file as input file.\n";
} elsif ($ARGV[0] == 1) { 
    # dummy argument to move on to rest of arg list
    shift;
}

# if first arg is nrnmodl just run nrnmodl else
# take the first arg to be a file name if it exists
if ($ARGV[0] eq "nrnmodl") {
    $filecreate = 0; shift;
} elsif ($ARGV[0] eq "create") { 
    $nrnmodlflag = 0; shift;
} elsif ($ARGV[0] eq "nrnoc") { 
    $nrnmodl = "$neuronhome/bin/nrnocmodl"; shift;
} elsif ($ARGV[0] eq "profile") { 
    $nrnmodl = "/usr/local/src/nrniv/local/bin/nrnivmodl.prof"; shift;
} elsif ($ARGV[0] eq "condor") { 
    $condor = 1;
    $filecreate = 0;
    print "Using $neuronhome/bin/nrnivmodl\n";
    $nrnmodl = "condor_compile $neuronhome/bin/nrnivmodl"; shift;
} elsif ($ARGV[0] eq "condordebug") { 
    $condor = 1;
    $filecreate = 0;
    print "Using $neuronhome/bin/nrnivmodl.condor.debug\n";
    $nrnmodl = "condor_compile $neuronhome/bin/nrnivmodl.condor.debug"; shift;
} elsif ($ARGV[0] eq "localcondor") { 
    $condor = 1;
    $filecreate = 0;
    $nrnmodl = "/usr/local/src/nrniv/local/bin/nrnivmodl.localcondor"; shift;
} elsif ($ARGV[0] eq "ldflags") {
    shift;
    $nrnmodl = qq|nrnivmodl -loadflags "$ARGV[0]"|; shift
} elsif ($ARGV[0] eq "nocmodl") { 
    $nrnmodl = "$neuronhome/bin/nrnocmodl"; 
    $filecreate = 0; shift;
} elsif ($ARGV[0] eq "clean") { 
    $nrnmodlflag = 0; $filecreate = 0; $clean = 1; shift;
} elsif ($ARGV[0] eq "files") {
    shift; $grep = "@ARGV"; $#ARGV=-1; # clear out rest of the args 
    $nrnmodlflag = 0; $filecreate = 0; $fullname=1; 
} elsif ($ARGV[0] eq "tar") {
    shift; @ATAR = @ARGV; $#ARGV=-1; # clear out rest of the args 
    $nrnmodlflag = 0; $filecreate = 0; $fullname=1;  $tar=1;
} elsif ($ARGV[0] eq "zip") {
    shift; 
    if ($ARGV[0] =~ /-f/) { # a list of additional files
      open(F,$ARGV[1]);
      while (<F>) {chop; push(@ATAR,$_);}
    } else {
      @ATAR = @ARGV; $#ARGV=-1; # clear out rest of the args 
    }
    $nrnmodlflag = 0; $filecreate = 0; $fullname=1;  $tar=2;
} elsif ($ARGV[0] eq "grep") {
    shift; $grep = "@ARGV"; $#ARGV=-1; # clear out rest of the args 
    $nrnmodlflag = 0; $filecreate = 0;
} elsif ($ARGV[0] eq "help") { 
    shift;
    die "\nnrnmodl [filename] [flag or [mech1 mech2 ...]]
      if filename is not given assumed to be parameters.multi
      name can be given fully or with .multi assumed

    possible flags are:
      create - produce new .mod files but do not run nrnmodl
      nrnmodl - just run nrnmodl, all .mod files should already be present
      nrnoc or nocmodl  - run $neuronhome/bin/nrnocmodl
      grep - just show the compile command

    if mech names are given only these will be recreated for recompilation
\n";
}

if ($#ARGV > -1) {
    print "Only recompile: @ARGV\n";
    grep($sections{$_}=1,@ARGV); # convert to associative array
}    

# file to read from, usually parameters.multi
if (!open(IN,$file)) { `nrnivmodl`; exit; }

# will use MODL_INCLUDE path to look for .mod files
@modpath = split(/[ :]/,$ENV{MODL_INCLUDE});
$site = ($ENV{SITE} or "/usr/site");
print "Search path for mod files is @modpath\n";

# block starts with NEURON { SUFFIX NAME }
$block_regexp = '^NEURON\s*{\s*((POINT_PROCESS)|(SUFFIX))\s+(\w+)';
@lines = ();			# save lines for blocks of statements
$curfile = "";			# name of file for a given block
(! -l "../$uname") and (symlink("mod/$uname","../$uname") || die "ERROR: Can't create link from ../$uname\n");

while (<IN>) {
  if ($_ =~ /$block_regexp/) {
    $curfile && &printit;	# print the previous block
    $curfile = $4;		# name comes from the 4th parenset in block_regexp
    if ($clean && -f ($objfile = $ENV{"CPU"}."/".$curfile.".o")) {
      print "Remove $objfile.\n"; unlink($objfile);
    }
    push(@lines,$_);

  } elsif ($_ =~ /^LDFLAGS (.+)/) {
    $loadflags .= qq| $1|;
  } elsif ($_ =~ /^DEFAULT/) {
    $curfile && &printit;	# finish off a block if needed
    split; $filename = $_[1].".mod";
    push(@modfiles,$_[1]);	# stem only to run nrnmodl on
    if (($clean || $sections{$_[1]}) && -f ($objfile = $ENV{"CPU"}."/".$_[1].".o")) {
      print "Remove: $objfile.\n"; unlink($objfile);
    }
    if ($_[2] =~ /[0-9]+/ && $filecreate) { # a version number
      $co = 0;			# a flag
      if (-e "RCS/$filename,v") {
	print "Checking out version 1.$_[2] of $filename.\n";
	$co = 1;
	`co -r1.$_[2] $filename`;
      } else {
	foreach $dir (@modpath) { # look for the file and create link
	  if (-e "$dir/RCS/$filename,v") { # save and terminate loop
	    print "Checking out version 1.$_[2] of $dir/$filename.\n";
	    unlink($filename);
	    # must use full RCS path to get file into current dir
	    # instead of into remote directory
	    `co -r1.$_[2] $dir/RCS/$filename,v`;
	    $co = 1;
	    last; 
	  }
	}
      }
      ($co==1) || die "WARNING RCS VERSION FOR $filename NOT FOUND.\n";
      # look for the file in MODL_INCLUDE path
    } elsif (-e $filename) {	
      $co = 1;
    } else {
      $co = 0;
      foreach $dir (@modpath) { # look for the file and create link
	if (-e "$dir/$filename") { # save and terminate loop
	  $co = 1;
	  symlink("$dir/$filename",$filename) || die "can't link to $dir/$filename\n";
	  last;
	}
      }
    }
    if ($co == 0 && $filecreate) { # couldn't find the file so look for RCS
      if (-e "RCS/$filename,v") {
	print "Checking out $filename.\n";
	$co = 1; `co $filename`;
      } else {
	foreach $dir (@modpath) { # look for the file and create link
	  if (-e "$dir/RCS/$filename,v") { # save and terminate loop
	    print "Checking out $dir/$filename.\n";
	    `co $dir/$filename`;
	    symlink("$dir/$filename",$filename);
	    $co = 1;
	    last; 
	  }
	}
      }
    }
    if (`grep -c //@ $filename`+0 > 0) { # look for '//@' which will need processing
      push(@modfiles,pop(@modfiles)."_"); # stem_
      $f1="$modfiles[$#modfiles].mod";
      if ((! -f $f1) || (-M $filename < -M $f1)) {
	&verbatize($filename); # replace //@ with bracketing VERBATIM/ENDVERBATIM
      }
    }
    ($co==1) || die "$filename NOT FOUND; check env variable MODL_INCLUDE.\n";
  } elsif ($#lines >= 0) {  	# only add lines if in a block
    push(@lines,$_);
  }
}

# need to do terminal check
$curfile && &printit;

$nrnmodlflag || print "COMPILATION COMMAND: \n";
# tell user the mod files being included
print "\t$nrnmodl @modfiles\n"; 
if ($grep) {
    grep($_.=".mod",@modfiles); # put .mod back on ends for filenames
    print "grep $grep @modfiles\n";
    system("grep $grep @modfiles");
}
if ($fullname) {
    grep($_.=".mod",@modfiles); # put .mod back on ends for filenames
    open(GREP,"grep INCLUDE @modfiles|");
    while (<GREP>) {
      if (/"/) { 
         s/[^"]+"([^"]+)"/\1/;
	 $filename=$_; chop $filename;
	 if (grep($_ eq $filename,@modfiles)) { next; }
	 push(@modfiles,$filename);
         if (! -e $filename) {	
	   foreach $dir (@modpath) { # look for the file and create link
	     if (-e "$dir/$filename") { # save and terminate loop
	       symlink("$dir/$filename",$filename) || die "can't link to $dir/$filename\n";
	       last;
	     }
	   }
	 }
       }
    }
    print "\n\t@modfiles\n";
    if ($tar) {
      $dstr = "b".`datestring`;
      print (($tar==1)?
	     "Creating $dstr.tar; use 'tar rhf $dstr.tar $dstr/filename' if need to append\n":
	     "Creating $dstr.zip; use 'zip -g $dstr.zip $dstr/filename' if need to append\n");
      symlink(".",$dstr);
      if (-e "../batch_.hoc"){
	symlink("../batch_.hoc","batch_.hoc"); 
	push(@modfiles,"batch_.hoc"); 
      } else {
	print "\tNO batch_.hoc\n";
      }
      symlink("$site/nrniv/local/mod/misc.h","misc.h"); 
      push(@modfiles,"misc.h"); 
      if (! -e "data") {
	mkdir data;
	push(@modfiles,"data"); 
      } else {
	print "data/ dir exists -- not including\n";
      }
      foreach $file (@ATAR) { 
	($d,$f)= ($file =~ m|^(.+)/([^/]+)$|);
	if ($d!~/^$/) {
	  symlink("$file","$f");  
	  push(@links,$f);
	} else {
	  $f=$file;
	}
	push(@modfiles,$f);
      }
      grep($_="$dstr/$_",@modfiles);
      if ($tar==1) {`tar czhf $dstr.tgz @modfiles`;} else {
	unlink $dstr.zip;
	`zip $dstr.zip @modfiles`;
      }
      unlink $dstr;
      unlink @links;
    }
}
if ($nrnmodlflag) {
    if ($loadflags) { $nrnmodl .= qq| -loadflags "$loadflags"|; }
    (system("export DEFAULT_INCLUDES=-I/$site/nrniv/local/mod;$nrnmodl @modfiles") == 0) || 
      die "ERROR IN COMPILATION\n";
}

if ($nsp) {   # new special
  open(IN,$oldsp);
  open(OUT,"> $newsp");
  while (<IN>) {
    $_ =~ /libnrnmech/ and s|$uname/.libs/libnrnmech.so|$newlib|;
    print OUT;
  }
  close IN; close OUT; chmod 0755, $newsp;
  print "\t******** Moving special to $newsp ********\n";
  rename($oldlib,$newlib);
  rename("spe.SAV",$oldsp);
  rename("lib.SAV",$oldlib);
}

# print lines into a new file called $curfile.mod
# clear the lines array and the curfile name
sub printit { 
    push(@modfiles,$curfile);	# name of a file to run nrnmodl on
    if ($filecreate && (! %sections || $sections{$curfile})) {
	$curfile .= ".mod";	# real file name
	if ((! -f $curfile) || (-M $file < -M $curfile)) {
	  print "Creating $curfile\n";
	  open(OUT,"> $curfile") || die "Can't open $curfile.\n";
	  print OUT @lines;
	  close(OUT);
	}
    }
    @lines = ();		# clear the array
    $curfile = "";
}

# verbatize makes a line marked by //@ into a VERBATIM block
# need to sheer off the '{' and anything following so that brackets match for nocmodl
# NB can't use if/else block where the if is VERBATIM since then the else is unprecedented
# for nocmodl
sub verbatize {
  ($in)=@_;
  $out=$in; $out=~s/\.mod/_.mod/;
  open(I,"<$in"); open(O,">$out"); 
  while (<I>) {
    if (m|//@|) {
      if (m|([^{]+)({.+)//.+|) {
	print O "VERBATIM\n$1\nENDVERBATIM\n$2\n";
      } else {
	print O "VERBATIM\n$_\nENDVERBATIM\n";
      }
    } else {
      print O;
    }
  }
}

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