{ "metadata": { "name": "" }, "nbformat": 3, "nbformat_minor": 0, "worksheets": [ { "cells": [ { "cell_type": "code", "collapsed": false, "input": [ "import pickle\n", "import numpy as np\n", "import matplotlib.pyplot as plt\n", "from neuron import h,gui\n", "\n", "####Sections and Connections####\n", "nofsections = 27 # 1soma + 25dendritic sections + 1terminating section \n", "nofspines =1 # number of spines is 1 throughout this simulation\n", "\n", "gc=[h.Section() for i in range(nofsections)]\n", "spineh=[h.Section() for i in range(nofspines)]\n", "spinen=[h.Section() for i in range(nofspines)]\n", "\n", "for i in range(nofsections-1):\n", " gc[i+1].connect(gc[i],1,0)\n", "for i in range(nofspines):\n", " spineh[i].connect(spinen[i],0,1)\n", " \n", "j=0\n", "for i in range(nofspines): #spines start at 100um from soma, on 11th dendritic section\n", " spinen[i].connect(gc[11+j],0.5,1)\n", " j=j+1\n", " \n", "####Morphology and other Parameters#### \n", "h.celsius=22 #temperature\n", "h.dt=0.025 #temporal resolution,ms\n", "\n", "for i in range(nofsections): \n", " gc[i].L=10 #dendrite total length is 260 um\n", " gc[i].nseg=3\n", " gc[i].Ra=200\n", " \n", "gc[0].diam=10 #soma size is 10umx10um, and there are two tapering regimes:\n", "for i in range(1,11):#1.tapering starts at 2.35um, ends at 1.7um , first 10 sections as in Ona-Jodar et al. Front Cell Neurosci 2017 \n", " gc[i].diam=2.35-(i-1)*((2.35-1.7)/9)\n", "for i in range(11,27):#2.tapering starts at 1.7um ends at 1.2um, next 15 sections \n", " gc[i].diam=1.7-(i-10)*((1.7-1.2)/16)\n", " \n", "for i in range(nofspines): \n", " spineh[i].diam=1\n", " spinen[i].diam=0.3 \n", " spineh[i].L=1\n", " spinen[i].L=2.5\n", " spineh[i].nseg=3\n", " spinen[i].nseg=3\n", " spinen[i].Ra=4.9e3 #Ra is normalized as ohmcm.\n", " \n", "presyn=h.Section() #with all other default specifications\n", "presyn.L=10\n", "presyn.diam=10\n", "\n", "####Settings for Ion channels and Synaptic Receptors and their Parameters#### \n", "for i in range(nofsections):\n", " gc[i].insert('constant')#dummy current source\n", " gc[i].insert('cadifusnpumpOGBenddif')#ca and buffers diffusion,ca pumps \n", " gc[i].insert('nax')\n", " gc[i].insert('kamt')\n", " gc[i].insert('pas')\n", " gc[i].g_pas=6e-4 \n", " gc[i].e_pas=-85\n", " gc[i].gbar_nax=0.5\n", " gc[i].gbar_kamt=0.01\n", " gc[i].cm=1\n", " \n", " gc[i].insert('canhem')#HVA Ca2+ channel \n", " gc[i].insert('cathem')#T-type Ca2+ channel\n", " gc[i].q10_cathem=3\n", " gc[i].q10_canhem=3 \n", " gc[i].a0m_cathem=0.055633 #to adjust the opening rate\n", " gc[i].a0m_canhem=0.331432 #to adjust the opening rate \n", " gc[i].gcanbar_canhem=0.0005\n", " gc[i].gcatbar_cathem=0.0003\n", " \n", " gc[i].TotalPump_cadifusnpumpOGBenddif=2e-11 \n", " \n", "for i in range(nofspines): \n", " spineh[i].insert('constant')#dummy current source\n", " spineh[i].insert('cadifusnpumpOGBenddif')#ca and buffers diffusion,ca pumps \n", " spineh[i].insert('nax')\n", " spineh[i].insert('kamt')\n", " spineh[i].insert('pas')\n", " spineh[i].gbar_nax=0.5\n", " spineh[i].gbar_kamt=0.01\n", " spineh[i].g_pas=2e-4\n", " spineh[i].e_pas=-85\n", " spineh[i].cm=1\n", "\n", " spineh[i].insert('canhem')\n", " spineh[i].insert('cathem')\n", " spineh[i].q10_canhem=3\n", " spineh[i].q10_cathem=3\n", " spineh[i].a0m_cathem=0.055633 #to adjust the opening rate\n", " spineh[i].a0m_canhem=0.331432 #to adjust the opening rate\n", " spineh[i].gcatbar_cathem=0.00015 \n", " spineh[i].gcanbar_canhem=0.0004 \n", "\n", " spineh[i].TotalPump_cadifusnpumpOGBenddif=2.2e-11 \n", " \n", "AMPARsyn=[h.AMPA5() for i in range(nofspines)]\n", "NMDARsyn=[h.NMDA5() for i in range(nofspines)]\n", "\n", "for i in range(nofspines): \n", " AMPARsyn[i].loc(spineh[i](0.3))\n", " AMPARsyn[i].gmax=2000\n", " NMDARsyn[i].loc(spineh[i](0.7))\n", " NMDARsyn[i].gmax=383 \n", " NMDARsyn[i].gmax_ca=17 \n", " ##NMDAR Setting##\n", " NMDARsyn[i].Rb= 5e-3\n", " NMDARsyn[i].Ru=12.9e-3\n", " NMDARsyn[i].Rd=8.4e-3\n", " NMDARsyn[i].Rr=6.8e-3\n", " NMDARsyn[i].Ro=46.5e-3\n", " NMDARsyn[i].Rc=73.8e-3 \n", " ####\n", " spinen[i].insert('cadifusnpumpOGBenddif')\n", " spinen[i].TotalPump_cadifusnpumpOGBenddif=0 #there is no active mechanism on the neck\n", "\n", "####Setting Ca Dynamic Global Parameters####\n", "h.DCa_cadifusnpumpOGBenddif=0.6\n", "h.mg_NMDA5=1\n", "##endogenous buffer\n", "for i in range(nofsections):\n", " gc[i].k1buf1_cadifusnpumpOGBenddif=1000\n", " gc[i].k2buf1_cadifusnpumpOGBenddif=1\n", " gc[i].TotalBuffer1_cadifusnpumpOGBenddif=0.12\n", "for i in range(nofspines):\n", " spineh[i].k1buf1_cadifusnpumpOGBenddif=1000\n", " spineh[i].k2buf1_cadifusnpumpOGBenddif=1\n", " spineh[i].TotalBuffer1_cadifusnpumpOGBenddif=0.12\n", "##exogenous buffer \n", "for i in range(nofsections):\n", " gc[i].k1buf2_cadifusnpumpOGBenddif=1000\n", " gc[i].k2buf2_cadifusnpumpOGBenddif=0.2\n", " gc[i].TotalBuffer2_cadifusnpumpOGBenddif=0.1 #for \"no OGB case\", set this to 0\n", "for i in range(nofspines):\n", " spineh[i].k1buf2_cadifusnpumpOGBenddif=1000\n", " spineh[i].k2buf2_cadifusnpumpOGBenddif=0.2\n", " spineh[i].TotalBuffer2_cadifusnpumpOGBenddif=0.1 #for \"no OGB case\", set this to 0\n", "\n", "####Mapping of Ca Concentration to fluorescence signal df/f \u2013 based on experimental data and simulations, see Figure 3C; not valid for \"no OGB case\"####\n", "def spine_fit(x):\n", " y = 14390070 + (-49.1502 - 14390070)/(1 + (x/6632796000)**0.6715641)\n", " return y\n", " \n", "def dend_fit(x): #not calculated and used based on experiment\n", " y = 14390070 + (-49.1502 - 14390070)/(1 + (x/6632796000)**0.6715641)\n", " return y\n", "\n", "####Setting Stimulation####\n", "#Global action potential:\n", "APstim1=h.IClamp(0.5,sec=gc[0])\n", "APstim1.delay=30 \n", "APstim1.dur=3 \n", "APstim1.amp=0 #to produce AP stimulation set this to 1, otherwise to 0 \n", "#Glutamate\n", "Rel=h.STEP_REL(0.75,presyn)\n", "Rel.amplitude=1 #to produce Glu stimulation set this to 1, otherwise to 0\n", "Rel.duration=3\n", "Rel.release_time=30\n", "\n", "for i in range(nofspines):\n", " h.setpointer(Rel._ref_GLU,'C',AMPARsyn[i])\n", " h.setpointer(Rel._ref_GLU,'C',NMDARsyn[i])\n", " \n", "####Simulation Readout####\n", "time_h = h.Vector()\n", "time_h.record(h._ref_t)\n", "vrec_gc=[h.Vector() for i in range(nofsections)] #gc[0] is the soma, gc[10] is the 1th parent dendrite\n", "vrec_spineh=[h.Vector() for i in range(nofspines)] \n", "icaspineh=[h.Vector() for i in range(nofspines)] #overall influx\n", "ccaspineh=[h.Vector() for i in range(nofspines)] #overall concentration\n", "icagc=[h.Vector() for i in range(nofsections)] #overall influx\n", "ccagc=[h.Vector() for i in range(nofsections)] #overall concentration\n", "\n", "icanmdr=[h.Vector() for i in range(nofspines)]\n", "icahvacc=[h.Vector() for i in range(nofspines)]\n", "icattype=[h.Vector() for i in range(nofspines)]\n", "\n", "clampcurrent=h.Vector()\n", "\n", "for i in range(nofsections): \n", " vrec_gc[i].record(gc[i](0.5)._ref_v)\n", "for i in range(nofspines): \n", " vrec_spineh[i].record(spineh[i](0.5)._ref_v) \n", "\n", "clampcurrent.record(APstim1._ref_i)\n", "\n", "for i in range(nofspines): \n", " icahvacc[i].record(spineh[i](0.5)._ref_ica_canhem)\n", " icanmdr[i].record(NMDARsyn[i]._ref_ica)\n", " icattype[i].record(spineh[i](0.5)._ref_ica_cathem)\n", "\n", "for i in range(nofspines): \n", " icaspineh[i].record(spineh[i](0.5)._ref_ica)\n", " ccaspineh[i].record(spineh[i](0.5)._ref_caiav_cadifusnpumpOGBenddif)\n", " \n", "for i in range(nofsections):\n", " icagc[i].record(gc[i](0.5)._ref_ica)\n", " ccagc[i].record(gc[i](0.5)._ref_caiav_cadifusnpumpOGBenddif) \n", "\n", "####Running the Simulation####\n", "h.v_init=-85 #forced resting Vm for granule cells\n", "h.init()\n", "\n", "for l in range(nofsections):# dummy current source to compensate current caused by the forced Vm. \n", " gc[l].ic_constant=-(gc[l].ina+gc[l].ik+gc[l].ica)\n", "for l in range(nofspines): \n", " spineh[l].ic_constant=-(spineh[l].ina+spineh[l].ik+spineh[l].ica)\n", "\n", "if h.cvode.active():\n", " h.cvode.re_init()\n", "else:\n", " h.fcurrent()\n", "\n", "h.tstop =350\n", "h.run()\n", "\n", "#### Vectors and conversion of units (um to nm)####\n", "time_ar=np.asarray(time_h)\n", "clamp=np.asarray(clampcurrent)\n", "v_spineh=np.asarray(vrec_spineh[0])\n", "v_soma=np.asarray(vrec_gc[0])\n", "\n", "icanmdr_show=[np.array for i in range(nofspines)]\n", "icattype_show=[np.array for i in range(nofspines)]\n", "icahvacc_show=[np.array for i in range(nofspines)]\n", "ccaspineh_show=[np.array for i in range(nofspines)]\n", "icaspineh_show=[np.array for i in range(nofspines)]\n", "ccagc_show=[np.array for i in range(nofsections)]\n", "icagc_show=[np.array for i in range(nofsections)]\n", "\n", "for i in range(nofspines):\n", " ccaspineh_show[i]=1e6*np.asarray(ccaspineh[i])#converting to nM\n", " icanmdr_show[i]=(1e2*np.asarray(icanmdr[i]))/3.14 #converting nA to mA/cm2, spine area is (piXe-8)cm2 \n", " icahvacc_show[i]=np.asarray(icahvacc[i]) #mA/cm2\n", " icattype_show[i]=np.asarray(icattype[i]) #mA/cm2\n", " \n", "for i in range(nofsections):\n", " ccagc_show[i]=1e6*np.asarray(ccagc[i])#converting to nM\n", "\n", "####Mapping of Ca Concentration to df/f####\n", "y_dff_spineh=[np.array for i in range(nofspines)]\n", "y_dff_gc=[np.array for i in range(nofsections)]\n", "\n", "for i in range(nofspines): \n", " y_dff_spineh[i]=spine_fit(ccaspineh_show[i])\n", " \n", "for i in range(nofsections): \n", " y_dff_gc[i]=spine_fit(ccagc_show[i]) \n", " \n", "#####Sample Plotting####\n", "plt.subplot(3,2,1).set_title('Soma Vm')\n", "plt.plot(time_h,vrec_gc[0])\n", "plt.ylabel('mV')\n", "\n", "plt.subplot(3,2,2).set_title('Spinehead Vm')\n", "plt.plot(time_h,vrec_spineh[0])\n", "plt.ylabel('mV')\n", "\n", "plt.subplot(3,2,3).set_title('Spinehead icahvacc')\n", "plt.plot(time_h,icahvacc_show[0])\n", "\n", "plt.ylabel('mA/cm2')\n", "\n", "plt.subplot(3,2,4).set_title('Spinehead icanmdr')\n", "plt.plot(time_h,icanmdr_show[0])\n", "plt.ylabel('mA/cm2') \n", "\n", "plt.subplot(3,2,5).set_title('Spinehead icattype')\n", "plt.plot(time_h,icattype_show[0])\n", "plt.ylabel('mA/cm2') \n", "\n", "plt.subplot(3,2,6).set_title('Spinehead df/f')\n", "plt.plot(time_h,y_dff_spineh[0],'g') #for \"no OGB case\" use ccaspineh_show[0] with nM ylabel instead\n", "#plt.plot(time_h,ccaspineh_show[0])\n", "plt.ylabel('%')\n", "plt.show()\n", "\n", "####For saving data vectors use: np.savetxt('file name',vector name, fmt=\"%1.8f\")" ], "language": "python", "metadata": {}, "outputs": [], "prompt_number": 2 }, { "cell_type": "code", "collapsed": false, "input": [], "language": "python", "metadata": {}, "outputs": [] } ], "metadata": {} } ] }
