Effects of increasing CREB on storage and recall processes in a CA1 network (Bianchi et al. 2014)

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Accession:151126
Several recent results suggest that boosting the CREB pathway improves hippocampal-dependent memory in healthy rodents and restores this type of memory in an AD mouse model. However, not much is known about how CREB-dependent neuronal alterations in synaptic strength, excitability and LTP can boost memory formation in the complex architecture of a neuronal network. Using a model of a CA1 microcircuit, we investigate whether hippocampal CA1 pyramidal neuron properties altered by increasing CREB activity may contribute to improve memory storage and recall. With a set of patterns presented to a network, we find that the pattern recall quality under AD-like conditions is significantly better when boosting CREB function with respect to control. The results are robust and consistent upon increasing the synaptic damage expected by AD progression, supporting the idea that the use of CREB-based therapies could provide a new approach to treat AD.
Reference:
1 . Bianchi D, De Michele P, Marchetti C, Tirozzi B, Cuomo S, Marie H, Migliore M (2014) Effects of increasing CREB-dependent transcription on the storage and recall processes in a hippocampal CA1 microcircuit. Hippocampus 24:165-77 [PubMed]
Model Information (Click on a link to find other models with that property)
Model Type: Realistic Network;
Brain Region(s)/Organism:
Cell Type(s): Hippocampus CA1 pyramidal GLU cell; Hippocampus CA1 interneuron oriens alveus GABA cell; Hippocampus CA1 basket cell;
Channel(s): I Na,t; I A; I K; I M; I h; I K,Ca; I Calcium; I_AHP; I Cl, leak; Ca pump;
Gap Junctions:
Receptor(s): GabaA; GabaB; AMPA; NMDA;
Gene(s):
Transmitter(s): Gaba; Glutamate;
Simulation Environment: NEURON;
Model Concept(s): STDP; Aging/Alzheimer`s; Depolarization block; Storage/recall; CREB;
Implementer(s): Bianchi, Daniela [danielabianchi12 -at- gmail.com]; De Michele, Pasquale [pasquale.demichele at unina.it];
Search NeuronDB for information about:  Hippocampus CA1 pyramidal GLU cell; Hippocampus CA1 interneuron oriens alveus GABA cell; GabaA; GabaB; AMPA; NMDA; I Na,t; I A; I K; I M; I h; I K,Ca; I Calcium; I_AHP; I Cl, leak; Ca pump; Gaba; Glutamate;
% Plot voltage traces from example PC and INs


clear all 
close all

NCELL =235     % number of cells (neurons)
NPCELL = 100; % number of PC (output) cells
SPATT = 20;   % number of active cells per pattern
%init=50     %for serial version
init=100

MOLT_TH=100;  
MOLT_TH1=100;   % =10 for pure recall; =100 for storage
%MOLT_TH=2;   % for serial version
%MOLT_TH1=2;   % for serial version
RTIME = init+(250*MOLT_TH1);    % run time (msecs)
% ----- parallel version
%for storage phase
STIME = init+82*250; % init+250 to see the all interval
ETIME =STIME+1100;  %RTIME  to see the all interval
%for pure recall
%STIME = init+125; 
%ETIME = RTIME;
%--------------------
% ----- serial version
%STIME = init+125; 
%ETIME = STIME+3*125;
%------------------
STDPP= 0.60;
STDPD=0.80;
SETPATT=1;

stdpp=num2str(STDPP, '%.2f');
stdpd=num2str(STDPD,'%.2f');
setp=num2str(SETPATT,'%d');
spat=num2str(SPATT,'%d');
molt_theta=num2str(MOLT_TH);
molt_theta1=num2str(MOLT_TH1); 
creb='';  % write '_CREB' for CREB case
suffix='';  % write '_RECALL' for pure recall
lensuf=length(suffix);
fold='Results/bpattrun2/';   % directory for storage phase
%fold='Results/bpattrun/';      % directory for pure recall

 
NSTORE=1;
npatt=num2str(NSTORE)

ntot=2;   % number of cell to be printed
inp=num2str(6);  % INPR variable

ms=8;
lw=1;
nr = 4;
VMIN = -90;
VMAX = 50;
dt = 0.025;
 
for NPATT =1:1:1 % number of patterns


 if (NPATT==0) NPATT=1; end

   npat=num2str(NPATT)
    %namefold=strcat(fold,'MT_',molt_theta,'_NS_',npat,'_SET_',setp,'_INPR_',inp,suffix,creb);  %for serial version
    namefold=strcat(fold,'MT_',molt_theta,'_NS_',npatt,'_SPATT_',spat,'_STDPP_',stdpp,'_STDPD_',stdpd,'_SET_',setp,'_INPR_',inp,suffix,creb);
   dir2=strcat('../',namefold);
     cd(dir2)

   
     
    for kk=1:NPATT
      
    npat2=num2str(kk)    
    if (lensuf==0)
          FST = 'HAM_P0R'; 
     else
          FST = strcat('HAM_P',npat2,'R');   % spikes file
     end
    
    FSTEM=strcat(FST,npat2,'_')

    subplot(nr,1,1);
    FV = [FSTEM 'AAC.dat'];   % voltage file
    v = load(FV);  % load spike times
    t = (0:length(v)-1)*dt;       % extract times
    hold on;
    plot(t, v, 'k-');   % voltage trace
    title('Axo-axonic cell');
    ylabel('V (mV)');
    axis([STIME ETIME VMIN VMAX]);

    subplot(nr,1,2);
    FV = [FSTEM 'BC.dat'];   % voltage file
    v = load(FV);  % load spike times
    t = (0:length(v)-1)*dt;       % extract times
    hold on;
    plot(t, v, 'k-');   % voltage trace
    title('Basket cell');
    ylabel('V (mV)');
    axis([STIME ETIME VMIN VMAX]);

    subplot(nr,1,3);
    FV = [FSTEM 'BSC.dat'];   % voltage file
    v = load(FV);  % load spike times
    t = (0:length(v)-1)*dt;       % extract times
    hold on;
    plot(t, v, 'k-');   % voltage trace
    title('Bistratified cell');
    ylabel('V (mV)');
    axis([STIME ETIME VMIN VMAX]);

    subplot(nr,1,4);
    FV = [FSTEM 'OLM.dat'];   % voltage file
    v = load(FV);  % load spike times
    t = (0:length(v)-1)*dt;       % extract times
    hold on;
    plot(t, v, 'k-');   % voltage trace
    title('OLM cell');
    ylabel('V (mV)');
    xlabel('Time (msecs)');
    axis([STIME ETIME VMIN VMAX]);

     name1=strcat(FSTEM,'Intern.jpg');
    saveas(gcf,name1)

         for jj=0:ntot-1

                figure;
                ncellp=num2str(jj)

                figure(2)

                subplot(3,1,1);
                FV = [FSTEM 'pvsoma_',ncellp,'.dat'];   % voltage file
                v = load(FV);  % load spike times
                t = (0:length(v)-1)*dt;       % extract times
                hold on;
                plot(t, v, 'k-');   % voltage trace
                title('Pattern pyramidal cell Soma');
                ylabel('V (mV)');
                axis([STIME ETIME VMIN+10 VMAX-30]);

                subplot(3,1,2);
                FV2 = [FSTEM 'pvsr_',ncellp,'.dat'];   % voltage file
                v = load(FV2);  % load spike times
                t = (0:length(v)-1)*dt;       % extract times
                hold on;
                plot(t, v, 'k-');   % voltage trace
                title('Pattern pyramidal cell RadTmed');
                ylabel('V (mV)');
                axis([STIME ETIME VMIN+10 VMAX-30]);

                subplot(3,1,3);
                FV3 = [FSTEM 'pvslm_',ncellp,'.dat'];   % voltage file
                v = load(FV3);  % load spike times
                t = (0:length(v)-1)*dt;       % extract times
                hold on;
                plot(t, v, 'k-');   % voltage trace
                title('Pattern pyramidal cell LM');
                ylabel('V (mV)');
                xlabel('Time (msecs)');
                axis([STIME ETIME VMIN+10 VMAX-30]);

              name=strcat(FSTEM,'Vtraces',ncellp ,'.jpg');
              saveas(gcf,name)
              close all

         end 


    end  % for kk

end

tt=t';
 fid2=fopen('time.txt','w+')
 for i=1:length(tt)
 fprintf(fid2,'%.4f\n', tt(i));
 end
 
    

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