Estimating the modulatory effects of nanoparticles on neuronal circuits using computational upscaling

Figures & data

Figure 1 Schematic description of synaptic interconnections in the simplified computational model of thethalamocortical network.

Abbreviations: IN, interneurons; RTN, reticular thalamic cells; PY, pyramidalneurons; STC, specific thalamic cells; NSTC, nonspecific thalamic cells.

Table 1 Normalized amplitudes of I_Na before and after cAgNP addition (holding potential−70 mV; depolarization potential −20 mV)

cAgNP concentration	x̃abefore cAgNP normalized	x̃ after cAgNP normalized	σbbefore cAgNP normalized	σbafter cAgNP normalized	Δx̃c normalized
13 μMol (1/100)	1	0.91	0.14	0.12	0.09
16 μMol (1/80)	1	0.77	0.19	0.11	0.23
43 μMol (1/30)	1	0.52	0.18	0.09	0.48
130 μMol (1/10)	1	0.47	0.13	0.10	0.53
1.3 mMol (1/1)	1	0.31	0.13	0.23	0.69

Note:

a x̃ = Normalized average amplitude;

b σ = normalized standard deviation;

c Δx̃ = normalized difference between controls and cAgNP exposed cells.

Abbreviations: cAgNP, coated silver nanoparticles; mV, millivolt.

Figure 2 Local application of cAgNP to chromaffin cells. (A) A representativecurrrent-voltage (IV)-curve of a cell before and after application of cAgNP (16 μMol, gray;corresponding control, black). (B) records of I_Na before and after localapplication of cAgNP after 60 seconds (s) and 120 seconds.

Abbreviations: cAgNP, coated silver nanoparticles; I_Na, sodium current;ms, milliseconds; mV, millivolt; NP, nanoparticles; pA, picoampere.

Figure 3 Measured sodium current. Measured sodium current without (A) and with(B) cAgNP (solid lines, holding potential −70 mV, depolarization potential−20 mV), and the curve fits by DE (dashed lines).

Abbreviations: pA, picoampere;I_Na, sodium current; cAgNP, coated silvernanoparticles; NP, nanoparticles; DE, Differential-Evolution Algorithm.

Figure 4 Differences in percentages.

Notes: Differences of model fitted α_h, β_h,α_m, β_m, and G_Namax between the measured sodiumcurrent with cAgNP in 130 (μMol concentration and the corresponding controls. Theξ.13 (stim–time) is not considered.

Abbreviation: cAgNP, coated silver nanoparticles.

Figure 5 Currents for control. DE fittings (dashed lines) utilizing just the seven identifiedHodgkin–Huxley equation parameters (α_h, α_m, andβ_m) and the corresponding electrophysiologically measured currents for control(A) and cAgNP (130 μMol) transfected (B).

Abbreviations: pA, picoampere; I_Na, sodium current; cAgNP, coated silvernanoparticles; NP, nanoparticles; DE, Differential-Evolution Algorithm; ms, milliseconds.

Figure 6 Firing pattern differences of pyramidal neurons.

Note: Differences in firing patterns of PY1, PY2, PY3, and PY4 neuron for 4 secondsbefore and after cAgNP application in thalamic neurons.

Abbreviations: PY, pyramidal neurons; mV, millivolt; cAgNP, coated silvernanoparticles; NP, nanoparticles; ms, milliseconds.

Figure 7 Firing pattern differences in IN, RTN1, RTN, STC, NSTC neurons.

Note: Differences in firing patterns of IN, RTN1, RTN2, STC, and NSTC neuron for 4seconds before and after cAgNP application in RTN and STC neurons.

Abbreviations: IN, interneurons; mV, millivolt; STC, specific thalamic cells; NSTC,nonspecific thalamic cells; RTN, reticular thalamic cells; cAgNP, coated silver nanoparticles; ms,milliseconds, NP, nanoparticles.

Table 2 Changes in neuronal bursting after cAgNPs application

Neuron type	Interburst interval (ms)	σainterburst interval (ms)	~Interburst frequency (Hz)	Intraburst frequency (Hz)	σaintraburst frequency (Hz)
PY1 before cAgNP application	120	19	6.7	291	1
PY1 after cAgNP application	110	32	7.5	278.5	4.5
PY2 before cAgNP application	96	33	6.5	271	4
PY2 after cAgNP application	93	33	7.75	266.5	6.5
PY4 before cAgNP application	139	56	4.75	296	1
PY4 after cAgNP application	125	57	6.7	691.5	2.5
IN before cAgNP application	103	23	7.5	201	15.5
IN after cAgNP application	89	27	8	139	2.5
RTN1 before cAgNP application	68	15	7.5	348.5	49.5
RTN1 after cAgNP application	65	8	7.75	366	72
RTN2 before cAgNP application	75	15	7.5	293.5	35.5
RTN2 after cAgNP application	69	12	7.75	332.5	19.5

Note:

a Standard deviation.

Abbreviations: cAgNP, coated silver nanoparticles; Hz, hertz; ms, milliseconds; PY,pyramidal neurons; IN, interneurons; NP, nanoparticles; RTN, reticular thalamic cells.

Table S1 Amplitudes of I_Na before and after cAgNP addition as total values

cAgNP concentration	x̃abefore cAgNP in pA and (normalized)	x̃ after cAgNP in pA and (normalized)	σbbefore cAgNP in pA and (normalized)	σ after cAgNP in pA and (normalized)	Δx̃c in pA and (normalized)
1/100 (13 μMol)	634.2 (1)	579.3 (0.91)	86 (0.14)	77.5 (0.12)	54.90 (0.09)
1/80 (16 μMol)	613.4 (1)	472.3 (0.77)	116.6 (0.19)	67.5 (0.11)	141.1 (0.23)
1/30 (43 μMol)	731.9 (1)	382.9 (0.52)	129.8 (0.18)	66.6 (0.09)	349 (0.48)
1/10 (130 μMol)	824.7 (1)	384.85 (0.47)	105.6 (0.13)	84.3 (0.10)	439.9 (0.53)
1/1 (1.3 mMol)	609.3 (1)	190.4 (0.31)	81.4 (0.13)	141.28 (0.23)	418.90 (0.69)

Notes:

a x̃ = Average amplitude expressed as median value in pA;

b σ = Standard deviation;

c Δx̃ = Difference in median between controls and cAgNP exposed cells. Amplitudesof I_NA before and after cAgNP addition (holding potential −70 mV, depolarizationpotential −20 mV). The protocols of 80 controls and 45 cAgNP exposed chromaffin cells werecollected to serve as experimental data fundament, in particular 1.3 mMol = 15 controls + 6affected; 13 μMol = 15 controls + 10 affected; 16 μMol = 10.

Abbreviations: cAgNP, silver coated nanoparticles; mV, millivolt; pA,picoampere.