Transient extracellular application of gold nanostars increases hippocampal neuronal activity

Abstract

Background: With the increased use of nanoparticles in biomedical applications there is a growing need to understand the effects that nanoparticles may have on cell function. Identifying these effects and understanding the mechanism through which nanoparticles interfere with the normal functioning of a cell is necessary for any therapeutic or diagnostic application. The aim of this study is to evaluate if gold nanoparticles can affect the normal function of neurons, namely their activity and coding properties. Results: We synthesized star shaped gold nanoparticles of 180 nm average size. We applied the nanoparticles to acute mouse hippocampal slices while recording the action potentials from single neurons in the CA3 region. Our results show that CA3 hippocampal neurons increase their firing rate by 17% after the application of gold nanostars. The increase in excitability lasted for as much as 50 minutes after a transient 5 min application of the nanoparticles. Further analyses of the action potential shape and computational modeling suggest that nanoparticles block potassium channels responsible for the repolarization of the action potentials, thus allowing the cell to increase its firing rate.

Selective Targeting of Neurons with Inorganic Nanoparticles: Revealing the Crucial Role of Nanoparticle Surface Charge

“…For instance, similar NP–neuron interactions were observed for negative carbon black, hematite iron oxide, titanium dioxide, 15 and gold NPs. 18 , 24 However, the interactions in those studies, unlike those reported in this work, were investigated over prolonged time exposure (from few hours to days) and at different concentration ranges within them. In this work, we have conducted a systematic study on different NP materials, of different size, shape composition, and coating, and we have investigated the immediate effects of NPs just after their administration, within the first few minutes and at a rather low-concentration range.…”

“…For example, neurons cultured on multielectrode arrays (MEAs) exposed to carbon black (CB), hematite (Fe 2 O 3 ), and titanium dioxide (TiO 2 ) NPs display an acute, concentration-dependent alteration of spontaneous electrical activity. 15 An increased electrical excitability also occurs in mouse hippocampal slices exposed to star-shaped Au NPs, 18 an observation confirmed at the single neuron level by patch clamp recordings. 24 Moreover, as shown in another study, quantum dots (QDs) with a negative coating were preferentially internalized by neurons with respect to astrocytes, oligodendrocytes, or microglia, suggesting that the surface charge is critical for neuron-specific uptake.…”

“…to their neuronal toxicity and activity. 13 − 18 Since aberrant neuronal electrical activity is associated with most neurological diseases 19 , 20 and can be an early marker of neurotoxicity, 21 it is crucial to understand how NPs can modulate brain electrical function.…”

Neuronal Maturation-dependent Nano-Neuro Interaction and Modulation

“…26 It has been reported that the nano-neuro interaction depolarizes neuronal membrane potential, resulting in increased excitability and firing rate of individual neurons. 40, 41 The increase in the excitability of the neurons results in increased probability of burst discharge instead of single firing event. 42 Consequently, in the present study, as a result of nanoparticle binding to a fraction of neurons in the neuronal network, the excitability of only the neurons tagged with nanoparticles is expected to increase.…”