Search bioRxiv⌕ Search

Biology subjects

Nizamoglu, S.

Publications and source records attributed to Nizamoglu, S..

3 recordsLinked to original sources

Functional Human Retinohypothalamic Tract Assembloid Model for Circadian Rhythm Research

The retinohypothalamic tract (RHT) is the primary pathway for circadian photoentrainment. Rodent models exhibit a significant translational gap for human physiology due to their nocturnal nature. To overcome this, we developed a functional human RHT assembloid by fusing human pluripotent stem cell (hPSC) derived retinal and hypothalamus organoids. Characterization revealed mature retinal brush borders and the preservation of melanopsin-expressing intrinsically photosensitive retinal ganglion cells (ipRGCs) integrated via excitatory glutamatergic synapses. Multielectrode array (MEA) analysis confirmed synchronized network activity across the interface. The development of the human RHT assembloid represents a significant leap forward in chronobiology. The "gold standard" for circadian models--self-sustained gene expression oscillations--was demonstrated using a PER2::Luciferase reporter, showing robust 20- 30 hour rhythms. This validates the hypothalamic component as a functional "clock in a dish". This platform provides a readout to screen drugs or test light-pulse effects on circadian phase, directly modeling jet lag or phase-shifting. Overall, this model offers a high-fidelity system for investigating human-specific chronobiological mechanisms in vitro. Graphical Abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=75 SRC="FIGDIR/small/700761v1_ufig1.gif" ALT="Figure 1"> View larger version (27K): org.highwire.dtl.DTLVardef@1327027org.highwire.dtl.DTLVardef@61183corg.highwire.dtl.DTLVardef@7e280eorg.highwire.dtl.DTLVardef@77e7ce_HPS_FORMAT_FIGEXP M_FIG C_FIG

bioengineering↗

A Retina-inspired Optoelectronic Synapse Using Quantum Dots for Neuromorphic Photostimulation of Neurons

Neuromorphic electronics, inspired by the functions of neurons, have the potential to enable biomimetic communication with cells. Such systems require operation in aqueous environments, generation of sufficient levels of ionic currents for neurostimulation, and plasticity. However, their implementation requires a combination of separate devices, such as sensors, organic synaptic transistors, and stimulation electrodes. Here, we present a compact neuromorphic synapse that combines photodetection, memory, and neurostimulation functionalities all-in-one. The artificial photoreception is facilitated by a photovoltaic device based on cell-interfacing InP/ZnS quantum dots, which induces photo-faradaic charge-transfer mediated plasticity. The device sends excitatory post-synaptic currents exhibiting paired-pulse facilitation and post-tetanic potentiation to the hippocampal neurons via the biohybrid synapse. The electrophysiological recordings indicate modulation of the probability of action potential firing due to biomimetic temporal summation of excitatory post-synaptic currents. Our results pave the way for the development of novel bioinspired neuroprosthetics and soft robotics and highlight the potential of quantum dots for achieving versatile neuromorphic functionality in aqueous environments.

bioengineering↗

Plasmon-Coupled Photocapacitor Neuromodulators

Efficient transduction of optical energy to bioelectrical stimuli is an important goal for effective communication with biological systems. For that plasmonics has significant potential via boosting the light-matter interactions. However, plasmonics has been primarily used for heat-induced cell stimulation due to membrane capacitance change (i.e., optocapacitance). Instead, here we demonstrate that plasmonic coupling to photocapacitor biointerfaces improves safe and efficacious neuromodulating displacement charges for an average of 185% in the entire visible spectrum while maintaining the Faradaic currents below 1%. Hot-electron injection dominantly leads the enhancement of displacement current at blue spectral window, and nanoantenna effect is mainly responsible for the improvement at red-spectral region. The plasmonic photocapacitor facilitates wireless modulation of single cells at 3-orders of magnitude below the maximum retinal intensity levels corresponding to one of the most sensitive optoelectronic neural interfaces. This study introduces a new way of using plasmonics for safe and effective photostimulation of neurons and paves the way toward ultra-sensitive plasmon-assisted neurostimulation devices.

biophysics↗