This content will become publicly available on December 13, 2023
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- Proceedings of the National Academy of Sciences
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- National Science Foundation
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Abstract In biology, heterosynaptic plasticity maintains homeostasis in synaptic inputs during associative learning and memory, and initiates long-term changes in synaptic strengths that nonspecifically modulate different synapse types. In bioinspired neuromorphic circuits, heterosynaptic plasticity may be used to extend the functionality of two-terminal, biomimetic memristors. In this article, we explore how changes in the pH of droplet interface bilayer aqueous solutions modulate the memristive responses of a lipid bilayer membrane in the pH range 4.97–7.40. Surprisingly, we did not find conclusive evidence for pH-dependent shifts in the voltage thresholds ( V* ) needed for alamethicin ion channel formation in the membrane. However, we did observe a clear modulation in the dynamics of pore formation with pH in time-dependent, pulsed voltage experiments. Moreover, at the same voltage, lowering the pH resulted in higher steady-state currents because of increased numbers of conductive peptide ion channels in the membrane. This was due to increased partitioning of alamethicin monomers into the membrane at pH 4.97, which is below the pKa (~5.3–5.7) of carboxylate groups on the glutamate residues of the peptide, making the monomers more hydrophobic. Neutralization of the negative charges on these residues, under acidic conditions, increased the concentration of peptide monomers in the membrane, shifting the equilibrium concentrations of peptide aggregate assemblies in the membrane to favor greater numbers of larger, increasingly more conductive pores. It also increased the relaxation time constants for pore formation and decay, and enhanced short-term facilitation and depression of the switching characteristics of the device. Modulating these thresholds globally and independently of alamethicin concentration and applied voltage will enable the assembly of neuromorphic computational circuitry with enhanced functionality. Impact statement We describe how to use pH as a modulatory “interneuron” that changes the voltage-dependent memristance of alamethicin ion channels in lipid bilayers by changing the structure and dynamical properties of the bilayer. Having the ability to independently control the threshold levels for pore conduction from voltage or ion channel concentration enables additional levels of programmability in a neuromorphic system. In this article, we note that barriers to conduction from membrane-bound ion channels can be lowered by reducing solution pH, resulting in higher currents, and enhanced short-term learning behavior in the form of paired-pulse facilitation. Tuning threshold values with environmental variables, such as pH, provide additional training and learning algorithms that can be used to elicit complex functionality within spiking neural networks. Graphical abstractmore » « less
New parallel computing architectures based on neuromorphic computing are needed due to their advantages over conventional computation with regards to real‐time processing of unstructured sensory data such as image, video, or voice. However, developing artificial neuromorphic system remains a challenge due to the lack of electronic synaptic devices, which can mimic all the functions of biological synapses with low energy consumption. Here it is reported that two‐terminal organometal trihalide perovskite (OTP) synaptic devices can mimic the neuromorphic learning and remembering process. Various functions known in biological synapses are demonstrated in OTP synaptic devices including four forms of spike‐timing‐dependent plasticity (STDP), spike‐rate‐dependent plasticity (SRDP), short‐term plasticity (STP) and long‐term potentiation (LTP)), and learning‐experience behavior. The excellent photovoltaic property of the OTP devices also enables photo‐read synaptic functions. The perovskite synapse has the potential of low energy consumption of femto‐Joule/(100 nm)2per event, which is close to the energy consumption of biological synapses. The demonstration of energy‐efficient OTP synaptic devices opens a new plausible application of OTP materials into neuromorphic devices, which offer the high connectivity and high density required for biomimic computing.
Analysis of long‐term potentiation (LTP) provides a powerful window into cellular mechanisms of learning and memory. Prior work shows late LTP (L‐LTP), lasting >3 hr, occurs abruptly at postnatal day 12 (P12) in the
stratum radiatumof rat hippocampal area CA1. The goal here was to determine the developmental profile of synaptic plasticity leading to L‐LTP in the mouse hippocampus. Two mouse strains and two mutations known to affect synaptic plasticity were chosen: C57BL/6J and Fmr1 −/yon the C57BL/6J background, and 129SVE and Hevin−/−( Sparcl1−/−) on the 129SVE background. Like rats, hippocampal slices from all of the mice showed test pulse‐induced depression early during development that was gradually resolved with maturation by 5 weeks. All the mouse strains showed a gradual progression between P10‐P35 in the expression of short‐term potentiation (STP), lasting ≤1 hr. In the 129SVE mice, L‐LTP onset (>25% of slices) occurred by 3 weeks, reliable L‐LTP (>50% slices) was achieved by 4 weeks, and Hevin−/−advanced this profile by 1 week. In the C57BL/6J mice, L‐LTP onset occurred significantly later, over 3–4 weeks, and reliability was not achieved until 5 weeks. Although some of the Fmr1 −/ymice showed L‐LTP before 3 weeks, reliable L‐LTP also was not achieved until 5 weeks. L‐LTP onset was not advanced in any of the mouse genotypes by multiple bouts of theta‐burst stimulation at 90 or 180 min intervals. These findings show important species differences in the onset of STP and L‐LTP, which occur at the same age in rats but are sequentially acquired in mice.
Recently, several light‐stimulated artificial synaptic devices have been proposed to mimic photonic synaptic plasticity for neuromorphic computing. Here, the photoelectric synaptic plasticity based on 2D lead‐free perovskite ((PEA)2SnI4) is demonstrated. The devices show a photocurrent activation in response to a light stimulus in a neuron‐like way and exhibit several essential synaptic functions such as short‐term plasticity (STP) and long‐term plasticity (LTP) as well as their transmission based on spike frequency control. The strength of synaptic connectivity can be effectively modulated by the duration, irradiance, and wavelength of light spikes. The ternary structure of (PEA)2SnI4causes it to possess varied photoelectric properties by composition control, which enhances the complexity and freedoms required by neuromorphic computing. The physical mechanisms of the memory effect are attributed to two distinct lifetimes of photogenerated carrier trapping/detrapping processes modulated by controlling the proportion of Sn vacancies. This work demonstrates the great potential of (PEA)2SnI4as a platform to develop future multifunctional artificial neuromorphic systems.
Understanding the mechanisms of nanoparticle interaction with cell membranes is essential for designing materials for applications such as bioimaging and drug delivery, as well as for assessing engineered nanomaterial safety. Much attention has focused on nanoparticles that bind strongly to biological membranes or induce membrane damage, leading to adverse impacts on cells. More subtle effects on membrane function mediated via changes in biophysical properties of the phospholipid bilayer have received little study. Here, we combine electrophysiology measurements, infrared spectroscopy, and molecular dynamics simulations to obtain insight into a mode of nanoparticle-mediated modulation of membrane protein function that was previously only hinted at in prior work. Electrophysiology measurements on gramicidin A (gA) ion channels embedded in planar suspended lipid bilayers demonstrate that anionic gold nanoparticles (AuNPs) reduce channel activity and extend channel lifetimes without disrupting membrane integrity, in a manner consistent with changes in membrane mechanical properties. Vibrational spectroscopy indicates that AuNP interaction with the bilayer does not perturb the conformation of membrane-embedded gA. Molecular dynamics simulations reinforce the experimental findings, showing that anionic AuNPs do not directly interact with embedded gA channels but perturb the local properties of lipid bilayers. Our results are most consistent with a mechanism in which anionic AuNPs disrupt ion channel function in an indirect manner by altering the mechanical properties of the surrounding bilayer. Alteration of membrane mechanical properties represents a potentially important mechanism by which nanoparticles induce biological effects, as the function of many embedded membrane proteins depends on phospholipid bilayer biophysical properties.