### Here we find the minimum NaP Gbar that leads to bistability in valid unified models
import os
os.environ["OMP_NUM_THREADS"] = "1" # export OMP_NUM_THREADS=4
import sys
sys.path.insert(1, "../helperScripts")
sys.path.insert(1, "../Kinetics")
import numpy as np
import matplotlib.pyplot as plt
import features as fts
import MOOSEModel as mm
import expcells
import brute_curvefit as bcf
from copy import deepcopy
from tqdm import tqdm
import pandas as pd
from pprint import pprint
from goMultiprocessing import Multiprocessthis_appendsave
import pickle
import json
from scipy import signal
import warnings
import efel
# warnings.simplefilter(action="ignore", category=FutureWarning)
# warnings.simplefilter(action="ignore", category=RuntimeWarning)
# warnings.simplefilter(action="ignore", category=RuntimeError)
warnings.filterwarnings("ignore", category=DeprecationWarning)
Featurelist = [
"CellID",
# "E_rest_0",
# "Input resistance",
# "Cell capacitance",
# "Time constant",
# "sagV_m50",
# "sagrat_m50",
# "AP1_amp_1.5e-10",
# "APp_amp_1.5e-10",
# "AP1_time_1.5e-10",
# "APp_time_1.5e-10",
# "APavgpratio_amp_1.5e-10",
# "AP1_width_1.5e-10",
# "APp_width_1.5e-10",
# "AP1_thresh_1.5e-10",
# "APp_thresh_1.5e-10",
# "AP1_lat_1.5e-10",
# "ISI1_1.5e-10",
# "ISIl_1.5e-10",
# "ISIavg_1.5e-10",
"ISImedian_1.5e-10",
"freq_1.5e-10",
# "Adptn_id_1.5e-10",
# "fAHP_AP1_amp_1.5e-10",
# "DBLO_1.5e-10",
# "DBL_1.5e-10",
# "AP1_amp_3e-10",
# "APp_amp_3e-10",
# "AP1_time_3e-10",
# "APp_time_3e-10",
# "APavgpratio_amp_3e-10",
# "AP1_width_3e-10",
# "APp_width_3e-10",
# "AP1_thresh_3e-10",
# "APp_thresh_3e-10",
# "AP1_lat_3e-10",
# "ISI1_3e-10",
# "ISIl_3e-10",
# "ISIavg_3e-10",
# "ISImedian_3e-10",
# "freq_3e-10",
# "Adptn_id_3e-10",
# "fAHP_AP1_amp_3e-10",
# "DBLO_3e-10",
# "DBL_3e-10",
# "freq300to150ratio",
]
# pasmodelFlist = ['E_rest_0', 'Input resistance', 'Cell capacitance', 'Time constant', 'sagV_m50', 'sagrat_m50', "ISImedian_1.5e-10"]
### get exp cell features ###
LJP = 15e-3
samplingrate = 20000
df_expsummaryactiveF = pd.read_pickle(
"../helperScripts/expsummaryactiveF.pkl"
)
######################################################
stimamp = 30e-12
stim_start_chirp = 0.3
stim_end_chirp = 13.3
stim_start = 0.5
stim_end = 1
tstop = 14.5
stimlist_chirp = [
"soma",
"1",
".",
"inject",
f"(t>{stim_start_chirp} & t<{stim_end_chirp}) * sin(2*3.14159265359*(t-{stim_start_chirp})^3) * {stimamp}",
]
stimlist_chirp2 = [
"soma",
"1",
".",
"inject",
f"(t>{stim_start_chirp} & t<{stim_start_chirp+501}) * sin(2*3.14159265359*(t-{stim_start_chirp})^2) * {stimamp}",
]
stimlist_CC = [
"soma",
"1",
".",
"inject",
f"(t>{stim_start} & t<{stim_start+0.5}) * {-25e-12}",
]
stimlist_epsp = [
"soma",
"1",
".",
"inject",
f"(t>{stim_start} & t<{stim_start+0.5}) * {0e-12}",
]
stimlist_150pA = [
"soma",
"1",
".",
"inject",
f"(t>{stim_start} & t<{stim_start+0.5}) * {150e-12}",
]
stimlist_bis = [
"soma",
"1",
".",
"inject",
f"(t>{stim_start} & t<{stim_start+0.5}) * {150e-12} + (t>{stim_start+1} & t<{stim_start+1.5}) * {-50e-12}",
]
# Load models from the JSON file
basemodels_list = []
file_path = "activemodels_imp_Eb2_NaTallen.json"
with open(file_path, "r") as file:
for line in file:
basemodel = json.loads(line)
if (basemodel["Features"]["AP1_amp_1.5e-10"]>=df_expsummaryactiveF.loc["AP1_amp_1.5e-10", "10th quantile"]) & (basemodel["Features"]["AP1_amp_1.5e-10"]<=df_expsummaryactiveF.loc["AP1_amp_1.5e-10", "90th quantile"]):
if (basemodel["Features"]["AP1_width_1.5e-10"]>=df_expsummaryactiveF.loc["AP1_width_1.5e-10", "10th quantile"]) & (basemodel["Features"]["AP1_width_1.5e-10"]<=df_expsummaryactiveF.loc["AP1_width_1.5e-10", "90th quantile"]):
basemodels_list.append(basemodel)
######################################################################################
def findlowerbound(func, lower, upper, tol=1e-10, bis_lower=None, bis_upper=None, debug=False, **kwargs):
if debug:
print(lower, upper)
if bis_lower is None:
bis_lower = func(lower, **kwargs)
if bis_upper is None:
bis_upper = func(upper, **kwargs)
if upper-lower<tol and bis_lower==0:
print(lower)
return lower
elif upper-lower<tol and bis_upper==0:
print(upper)
return upper
elif upper-lower<tol and bis_lower!=0 and bis_upper!=0:
return None
doesitsatisfy = func((lower+upper)/2, **kwargs)
if doesitsatisfy==0 or doesitsatisfy==1:
return findlowerbound(func, lower, (lower+upper)/2, tol=tol, bis_lower=bis_lower, bis_upper=doesitsatisfy, debug=debug, **kwargs)
elif doesitsatisfy==-1:
return findlowerbound(func, (lower+upper)/2, upper, tol=tol, bis_lower=doesitsatisfy, bis_upper=bis_upper, debug=debug, **kwargs)
def ourfunc(Na_P_Gbar=1e-9, i=0):
model = deepcopy(basemodels_list[i])
# model["Parameters"]["Channels"]["h_Chan"]["Kinetics"] = baseModel["Parameters"]["Channels"]["h_Chan"]["Kinetics"]
# model["Parameters"]["Channels"]["Na_T_Chan"]["Kinetics"] = baseModel["Parameters"]["Channels"]["Na_T_Chan"]["Kinetics"]
# model["Parameters"]["Channels"]["K_DR_Chan"]["Kinetics"] = baseModel["Parameters"]["Channels"]["K_DR_Chan"]["Kinetics"]
model["Parameters"]["Channels"]["Na_P_Chan"] = {
"Gbar": 1e-9,
"Erev": 0.060,
"Kinetics": "../Kinetics/Na_P_Chan_Migliore2018",
"KineticVars": {"mvhalf": -50.4e-3, "mvslope": 4.53e-3}, #Migliore - {"mvhalf": -52.3e-3, "mvslope": 6.8e-3} #Brown1994 - {"mvhalf": -50.4e-3, "mvslope": 4.53e-3}
}
model["Parameters"]["Channels"]["Na_P_Chan"]["Gbar"] = Na_P_Gbar
### Get bis features #####
model["Features"] = {}
tvec, Ivec, Vmvec, Cavec = mm.runModel(
model,
CurrInjection=stimlist_bis,
vClamp=None,
refreshKin=True,
Truntime=2.5,
syn=False,
synwg=0,
synfq=5,
)
# plt.plot(tvec, Vmvec)
# plt.show()
tracebis = {}
tracebis["T"] = tvec * 1e3
tracebis["V"] = Vmvec * 1e3
###### 0pA condition #########
model["Features"]["E_rest"] = np.nanmedian(Vmvec[(tvec>=stim_start-0.1) & ((tvec<stim_start))])
tracebis["stim_start"] = [0]
tracebis["stim_end"] = [(stim_start) * 1e3]
tracebis["stimulus_current"] = [0e-3]
traces_results = efel.getFeatureValues(
[tracebis],
["Spikecount_stimint"],
)
trace_result = traces_results[0]
try:
if trace_result["Spikecount_stimint"][0] > 0: ########## Should not fire at 0pA
return 1 #-1 maane too much firing
if model["Features"]["E_rest"]>-0.070:
return 1
except Exception:
return 1
####### 150pA condition ###########
tracebis_ = {}
tracebis_["T"] = tvec[(tvec>=stim_start) & ((tvec<stim_start+0.5))] * 1e3
tracebis_["V"] = Vmvec[(tvec>=stim_start) & ((tvec<stim_start+0.5))] * 1e3
tracebis_["stim_start"] = [tracebis["T"][0]]
tracebis_["stim_end"] = [tracebis["T"][-1]]
tracebis_["stimulus_current"] = [150e-3]
traces_results = efel.getFeatureValues(
[tracebis_],
["Spikecount_stimint", "AP1_amp", "all_ISI_values", "min_between_peaks_values"],
)
trace_result = traces_results[0]
try:
# if (trace_result["Spikecount_stimint"][0]*2<df_expsummaryactiveF.loc["freq_1.5e-10", "10th quantile"]) or (trace_result["Spikecount_stimint"][0]*2>df_expsummaryactiveF.loc["freq_1.5e-10", "90th quantile"]):
# return [{}]
# if (np.nanmedian(trace_result["all_ISI_values"]) * 1e-3<df_expsummaryactiveF.loc["ISImedian_1.5e-10", "10th quantile"]) or (np.nanmedian(trace_result["all_ISI_values"]) * 1e-3>df_expsummaryactiveF.loc["ISImedian_1.5e-10", "90th quantile"]):
# return [{}]
# if (trace_result["AP1_amp"][0] * 1e-3 < df_expsummaryactiveF.loc["AP1_amp_1.5e-10", "10th quantile"]) or (trace_result["AP1_amp"][0] * 1e-3 > df_expsummaryactiveF.loc["AP1_amp_1.5e-10", "90th quantile"]):
# return [{}]
model["Features"]["freq_1.5e-10"] = trace_result["Spikecount_stimint"][0] * 2
model["Features"]["ISImedian_1.5e-10"] = (
np.nanmedian(trace_result["all_ISI_values"]) * 1e-3
)
model["Features"]["AP1_amp_1.5e-10"] = trace_result["AP1_amp"][0] * 1e-3
model["Features"]["DBLO_1.5e-10"] = (
np.nanmean(trace_result["min_between_peaks_values"]) * 1e-3
- model["Features"]["E_rest"]
)
model["Features"]["DBL_1.5e-10"] = (
np.nanmean(trace_result["min_between_peaks_values"]) * 1e-3
)
if trace_result["Spikecount_stimint"][0]*np.nanmean(trace_result["all_ISI_values"]) * 1e-3<0.45:
return 1 # 1 maane too much firing
# pprint(model["Features"])
except Exception:
return 1
####### second 0pA condition ###########
tracebis["stim_start"] = [(stim_start + 0.5) * 1e3]
tracebis["stim_end"] = [(stim_start + 1) * 1e3]
tracebis["stimulus_current"] = [0e-3]
traces_results = efel.getFeatureValues(
[tracebis],
["Spikecount_stimint"],
)
trace_result = traces_results[0]
try:
if trace_result["Spikecount_stimint"][0] < 2:
return -1
model["Features"]["freq_s0"] = trace_result["Spikecount_stimint"][0] * 2
# pprint(model["Features"])
except Exception:
return -1
######## -50pA condition ##############
tracebis["stim_start"] = [(stim_start + 1) * 1e3]
tracebis["stim_end"] = [(stim_start + 1.5) * 1e3]
tracebis["stimulus_current"] = [-50e-3]
traces_results = efel.getFeatureValues(
[tracebis],
["Spikecount_stimint"],
)
trace_result = traces_results[0]
try:
if (
trace_result["Spikecount_stimint"][0] >= 1
): ########## Should not fire at -50pA. Leeway of 2spikes due to Na resurgent firing
return 1
model["Features"]["freq_m50"] = trace_result["Spikecount_stimint"][0] * 2
# pprint(model["Features"])
except Exception:
return 1
####### third 0pA condition ###########
tracebis["stim_start"] = [(stim_start + 1.5) * 1e3]
tracebis["stim_end"] = [(stim_start + 2) * 1e3]
tracebis["stimulus_current"] = [0e-3]
traces_results = efel.getFeatureValues(
[tracebis],
["Spikecount_stimint"],
)
trace_result = traces_results[0]
try:
if (
trace_result["Spikecount_stimint"][0] >= 1
): ########## Should not fire at -50pA. Leeway of 1spikes due to Na resurgent firing
return 1
model["Features"]["freq_t0"] = trace_result["Spikecount_stimint"][0] * 2
# pprint(model["Features"])
except Exception:
return 1
# print("yoooohooooo", model["Features"]["DBLO_1.5e-10"])
return 0
lowerbound_list = []
def ourfunc_(i):
lowerbound = findlowerbound(ourfunc, 1e-10, 1e-6, tol=1e-12, bis_lower=None, bis_upper=None, debug=True, i=i)
return [lowerbound]
# for i in tqdm(range(len(basemodels_list))):
# lowerbound = ourfunc_(i)[0]
# print('##########################', lowerbound)
# lowerbound_list.append(lowerbound)
lowerbound_list = Multiprocessthis_appendsave(
ourfunc_, range(len(np.array(basemodels_list))), [lowerbound_list], [], seed=1213242, npool=110
)
np.save('Na_P_Gbar_lowerbound_bistable_unified.npy', lowerbound_list[0])