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

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"... 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. ... "
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]
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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 L5/6 pyramidal GLU cell; Neocortex L2/3 pyramidal GLU cell; Neocortex V1 interneuron basket PV GABA cell; Neocortex fast spiking (FS) interneuron; Neocortex spiny stellate cell; Neocortex spiking regular (RS) neuron; Neocortex spiking low threshold (LTS) neuron;
Gap Junctions:
Receptor(s): GabaA; AMPA; NMDA;
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 [bill.lytton at downstate.edu]; Neymotin, Sam [Samuel.Neymotin at nki.rfmh.org]; Rowan, Mark [m.s.rowan at cs.bham.ac.uk];
Search NeuronDB for information about:  Neocortex L5/6 pyramidal GLU cell; Neocortex L2/3 pyramidal GLU cell; Neocortex V1 interneuron basket PV GABA cell; GabaA; AMPA; NMDA; Gaba; Glutamate;
autotune.hoc *
basestdp.hoc *
batch.hoc *
batch2.hoc *
checkirreg.hoc *
col.dot *
col.hoc *
comppowspec.hoc *
condisconcellfig.hoc *
condisconpowfig.hoc *
declist.hoc *
decmat.hoc *
decnqs.hoc *
decvec.hoc *
default.hoc *
drline.hoc *
e2hubsdisconpow.hoc *
e2incconpow.hoc *
filtutils.hoc *
geom.hoc *
graphplug.hoc *
grvec.hoc *
infot.hoc *
init.hoc *
labels.hoc *
load.hoc *
local.hoc *
makepopspikenq.hoc *
matfftpowplug.hoc *
matpmtmplug.hoc *
matpmtmsubpopplug.hoc *
matspecplug.hoc *
network.hoc *
nload.hoc *
nqpplug.hoc *
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nqsnet.hoc *
nrnoc.hoc *
powchgtest.hoc *
python.hoc *
pywrap.hoc *
ratlfp.dat *
redE2.hoc *
setup.hoc *
shufmua.hoc *
simctrl.hoc *
spkts.hoc *
stats.hoc *
syncode.hoc *
vsampenplug.hoc *
xgetargs.hoc *
print "Loading writedata.hoc..."
// writedata.hoc
// Mark Rowan, School of Computer Science, University of Birmingham, UK
// March 2012

// Writes data in vit (and, possibly later, printlist and nqLFP) to disk
// periodically and flushes data from RAM, to enable very long simulations
// Data is stored in grvec format

// ***************************************************************************
// * run.hoc should have SPKSZ at least large enough to hold all the spikes
// generated by the network in "buffertime" ms.
// For the Alzheimer's tests, 1600s of ~20Hz stimulus to 470 cells produces > 3
// million spikes, so SPKSZ should be at least 3500e3 elements, and preferably
// a lot larger (given available RAM) in case there are periods with lots of spikes.
// This may take some experimentation as setting the Vector too large will result in
// running out of memory, but setting it too small means some spikes won't be recorded.
// Check your rasters and see if they contain spikes from start to end.
// * run.hoc should have the last line as prl(0,1) as currently printlist and
// nqLFP writing is not implemented, otherwise RAM usage will grow steadily as
// nqLFP / printlist object lists grow.
// * params.hoc should have "declare("use_nqLFP",0)" to prevent massive nqLFP
// vectors being initialised within each cell in run.hoc:wrecon().
// ***************************************************************************

// Set frequency of write operations
declare("buffertime", 1600e3) //16e3 // Write data to disk every buffertime ms of sim time

// Define objects
objref vitindexfile, vitdatafile // printlistvecfile, printlisttvecfile, nqLFPfile
strdef vitindexfilename, vitdatafilename // printlistvecfilename, printlisttvecfilename, nqLFPfilename
//strdef filepath // Needed if not passing filepath on the commandline. However, must be commented out if passing filepath on the commandline, or the supplied filepath will be overwritten by the strdef!

// Set up filenames
declare("filepath", "data") // Default save path (pass alternative paths to nrniv using '-c "filepath=..."' and ensure that 'strdef filepath' above is commented out)
sprint(vitindexfilename, "%s/%s", filepath, ".spks")
sprint(vitdatafilename, "%s/%s", filepath, "spks")
//sprint(printlistvecfilename, "%s%s%s", filepath, "printlist-vec", datetime)
//sprint(printlisttvecfilename, "%s%s%s", filepath, "printlist-tvec", datetime)
//sprint(nqLFPfilename, "%s%s%s", filepath, "nqLFP", datetime)

// Create files
vitindexfile = new File(vitindexfilename)
vitdatafile = new File(vitdatafilename)
//printlistvecfile = new File(printlistvecfilename)
//printlisttvecfile = new File(printlisttvecfilename)
//nqLFPfile = new File(nqLFPfilename)

proc writedata() { localobj vec

  // Open files for appending
  // Debug printouts (comment out for extra speed during write operations):
  printf("vit.vec has %d elements\n", vit.vec.size())
  vec = vit.vec.where("!=", 0)
  printf("writing %d elements\n", vec.size())

  // Write vitem object to file using grvec format
  // Can't just resize or delete/re-create Vectors, as the Vector pointers
  // are held by intf6.mod and are not reset to zero (so after x elements are
  // written and the Vector is resized, the next element will still be written
  // index x rather than beginning again at index 0).
  // Fortunately, intf6 provides a custom spike-to-file proc spkoutf:
  col.ce.o(0).spkoutf(vitindexfile,vitdatafile) // print spike and time data to file
  col.ce.o(0).spkoutf() // empty the spike data vectors and resize

  // printlist contains vitem objects (just like vit) so we need to loop through
  // printlist and write each object to file.
  // Currently not implemented as this requires a similar mechanism to
  // col.ce.o(0).spkoutf (above) but applied to the printlist objects.
  // nqLFP also currently not implemented.

  // Close files

  // Resize vit vectors to SPKSZ so they don't constantly shrink

  // Empty each of the printlist and nqLFP vectors and reclaim memory
  //prlclr() // Call prlclr() in run.hoc to clear printlist -- may also stop recording though?
  //wrecon() // Call wrecon() in run.hoc which reinitialises nqLFP. Is this correct?

 // Put next data write event onto queue to occur after t + buffertime
 cvode.event(t + buffertime,"writedata()") 

//* seteventqueue - starts off the event queue
proc seteventqueue() {
  // If mytstop is not a direct multiple of buffertime, then some data will remain
  // unsaved at the end of the simulation. So we find the amount by which we bring
  // forward the first write operation, so that the last write operation occurs at
  // the same time as the end of the simulation, meaning that all data is saved.
  // mytstop % buffertime ensures that we catch all the data
  cvode.event(t + buffertime + (mytstop % buffertime),"writedata()") 
declare("fith",new FInitializeHandler("seteventqueue()")) // Called as soon as INIT finishes