Mesoscopic model of spontaneous synaptic size fluctuations (Hazan & Ziv 2020)

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Accession:262060
Sizes of glutamatergic synapses vary tremendously, even when formed on the same neuron. This diversity is commonly thought to reflect the outcome of activity-dependent forms of synaptic plasticity, yet activity-independent processes might also play some part. Here we show that in neurons with no history of activity whatsoever, synaptic sizes are no less diverse. We show that this diversity is the product of activity-independent size fluctuations, which are sufficient to generate a full repertoire of synaptic sizes at correct proportions. By combining modeling and experimentation we expose reciprocal relationships between size fluctuations, synaptic sizes and synaptic counts, and show how these phenomena might be connected through the dynamics of synaptic molecules as they move in, out and between synapses.
Reference:
1 . Hazan L, Ziv NE (2020) Activity dependent and independent determinants of synaptic size diversity. J Neurosci [PubMed]
Model Information (Click on a link to find other models with that property)
Model Type: Synapse;
Brain Region(s)/Organism:
Cell Type(s):
Channel(s):
Gap Junctions:
Receptor(s):
Gene(s):
Transmitter(s):
Simulation Environment: C or C++ program;
Model Concept(s): Stochastic simulation; Synaptic noise; Reaction-diffusion;
Implementer(s): Ziv, Noam [noamz at netvision.net.il];
/*
------------------------------------------------------------------------------
rand.c: By Bob Jenkins.  My random number generator, ISAAC.  Public Domain.
MODIFIED:
  960327: Creation (addition of randinit, really)
  970719: use context, not global variables, for internal state
  980324: added main (ifdef'ed out), also rearranged randinit()
  010626: Note that this is public domain
------------------------------------------------------------------------------
*/
#ifndef STANDARD
#include "standard.h"
#endif
#ifndef RAND
#include "rand.h"
#endif


#define ind(mm,x)  (*(ub4 *)((ub1 *)(mm) + ((x) & ((RANDSIZ-1)<<2))))
#define rngstep(mix,a,b,mm,m,m2,r,x) \
{ \
  x = *m;  \
  a = (a^(mix)) + *(m2++); \
  *(m++) = y = ind(mm,x) + a + b; \
  *(r++) = b = ind(mm,y>>RANDSIZL) + x; \
}

void     isaac(ctx)
randctx *ctx;
{
   register ub4 a,b,x,y,*m,*mm,*m2,*r,*mend;
   mm=ctx->randmem; r=ctx->randrsl;
   a = ctx->randa; b = ctx->randb + (++ctx->randc);
   for (m = mm, mend = m2 = m+(RANDSIZ/2); m<mend; )
   {
      rngstep( a<<13, a, b, mm, m, m2, r, x);
      rngstep( a>>6 , a, b, mm, m, m2, r, x);
      rngstep( a<<2 , a, b, mm, m, m2, r, x);
      rngstep( a>>16, a, b, mm, m, m2, r, x);
   }
   for (m2 = mm; m2<mend; )
   {
      rngstep( a<<13, a, b, mm, m, m2, r, x);
      rngstep( a>>6 , a, b, mm, m, m2, r, x);
      rngstep( a<<2 , a, b, mm, m, m2, r, x);
      rngstep( a>>16, a, b, mm, m, m2, r, x);
   }
   ctx->randb = b; ctx->randa = a;
}


#define mix(a,b,c,d,e,f,g,h) \
{ \
   a^=b<<11; d+=a; b+=c; \
   b^=c>>2;  e+=b; c+=d; \
   c^=d<<8;  f+=c; d+=e; \
   d^=e>>16; g+=d; e+=f; \
   e^=f<<10; h+=e; f+=g; \
   f^=g>>4;  a+=f; g+=h; \
   g^=h<<8;  b+=g; h+=a; \
   h^=a>>9;  c+=h; a+=b; \
}

/* if (flag==TRUE), then use the contents of randrsl[] to initialize mm[]. */
void randinit(ctx, flag)
randctx *ctx;
word     flag;
{
   word i;
   ub4 a,b,c,d,e,f,g,h;
   ub4 *m,*r;
   ctx->randa = ctx->randb = ctx->randc = 0;
   m=ctx->randmem;
   r=ctx->randrsl;
   a=b=c=d=e=f=g=h=0x9e3779b9;  /* the golden ratio */

   for (i=0; i<4; ++i)          /* scramble it */
   {
     mix(a,b,c,d,e,f,g,h);
   }

   if (flag) 
   {
     /* initialize using the contents of r[] as the seed */
     for (i=0; i<RANDSIZ; i+=8)
     {
       a+=r[i  ]; b+=r[i+1]; c+=r[i+2]; d+=r[i+3];
       e+=r[i+4]; f+=r[i+5]; g+=r[i+6]; h+=r[i+7];
       mix(a,b,c,d,e,f,g,h);
       m[i  ]=a; m[i+1]=b; m[i+2]=c; m[i+3]=d;
       m[i+4]=e; m[i+5]=f; m[i+6]=g; m[i+7]=h;
     }
     /* do a second pass to make all of the seed affect all of m */
     for (i=0; i<RANDSIZ; i+=8)
     {
       a+=m[i  ]; b+=m[i+1]; c+=m[i+2]; d+=m[i+3];
       e+=m[i+4]; f+=m[i+5]; g+=m[i+6]; h+=m[i+7];
       mix(a,b,c,d,e,f,g,h);
       m[i  ]=a; m[i+1]=b; m[i+2]=c; m[i+3]=d;
       m[i+4]=e; m[i+5]=f; m[i+6]=g; m[i+7]=h;
     }
   }
   else
   {
     /* fill in m[] with messy stuff */
     for (i=0; i<RANDSIZ; i+=8)
     {
       mix(a,b,c,d,e,f,g,h);
       m[i  ]=a; m[i+1]=b; m[i+2]=c; m[i+3]=d;
       m[i+4]=e; m[i+5]=f; m[i+6]=g; m[i+7]=h;
     }
   }

   isaac(ctx);            /* fill in the first set of results */
   ctx->randcnt=RANDSIZ;  /* prepare to use the first set of results */
}


#ifdef NEVER
int main()
{
  ub4 i,j;
  randctx ctx;
  ctx.randa=ctx.randb=ctx.randc=(ub4)0;
  for (i=0; i<256; ++i) ctx.randrsl[i]=(ub4)0;
  randinit(&ctx, TRUE);
  for (i=0; i<2; ++i)
  {
    isaac(&ctx);
    for (j=0; j<256; ++j)
    {
      printf("%.8lx",ctx.randrsl[j]);
      if ((j&7)==7) printf("\n");
    }
  }
}
#endif

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