Biology subjects

Movahed, M.

Publications and source records attributed to Movahed, M..

4 recordsLinked to original sources

bioRxiv2025

Nanophotonic neural probes for in vivo photostimulation, electrophysiology, and microfluidic delivery

Implantable silicon neural probes with integrated optical emitters and electrodes are emerging tools for simultaneous optogenetic stimulation and electrophysiological recording in deep brain regions. In parallel, neural probes with microfluidic channels have been developed for localized drug delivery and neurochemical sampling. However, thus far, such fluidic probes have lacked optical and electrical functionalities or been limited to a low number of optical emitters and/or electrodes, constraining their utility in multimodal investigations of neural circuits. Here, we introduce foundry-fabricated silicon nanophotonic neural probes with monolithically integrated microfluidics. Each probe has 16 silicon nitride grating coupler emitters, 18 titanium nitride microelectrodes, and one embedded microfluidic channel. We evaluate the photonic, electrophysiological, and microfluidic functionalities in vivo in optogenetic, blue-light-sensitive mice. With our multifunctional neural probes, we demonstrate local suppression of epileptic seizure activity (induced by microfluidic injection of 4-aminopyridine) using photostimulation. Through foundry-compatible microfluidics integration, this work advances the versatility of nanophotonic neural probes and presents new possibilities for multimodal neuroscience experiments leveraging this scalable neurotechnology.

neuroscience↗

bioRxiv2025

Hyperpolarization activated cation channel mediated intrinsic plasticity changes underlie the malleability of with-in cell-type electrophysiological heterogeneity

Within cell-type neuronal electrophysiological, morphological, and transcriptomic heterogeneity is the norm in the brain. Although generally considered a fixed property within cell-types, this heterogeneity is malleable and declines in regions of the human brain that generate seizures. Building off this foundational work we hypothesize that such plasticity of cell-type heterogeneity, specifically its decline, arises from the shared history of neuronal activity that drive intrinsic plasticity mechanisms in a concerted fashion. To explore this hypothesis we study neuronal activity in two model systems: human cortical slice cultures from patients with epilepsy as well as slices from the medial prefrontal cortex (mPFC) and subiculum of rodent kainic acid (KA) model of temporal lobe epilepsy. Biophysical properties and spiking dynamics were characterized using whole-cell patch clamp recordings of layer 2 and layer 3 (L2&3) pyramidal neurons in human slice culture as well as deep layer subicular neurons and layer 5 (L5) mPFC of KA mice. We found a significant decline in biophysical heterogeneity and a reduction in information coding in both the KA and slice culture models. In both these models we found a consistent increase in hyperpolarization-activated cation current (HCN) dependent electrophysiological properties, the blockade of which restored electrophysiological heterogeneity and information coding. Our findings demonstrate that within cell-type heterogeneity is malleable, and despite being a complex distributed network property, can be tuned by a single ionic current. These findings emphasize the plasticity of within cell-type heterogeneity, suggesting the potential for targeted interventions to restore neuronal heterogeneity changes that accompany epilepsy and potentially other neurological and neuropsychiatric diseases.

neuroscience↗

bioRxiv2023

Implantable nanophotonic neural probes for integrated patterned photostimulation and electrophysiology recording

Optogenetics has transformed neuroscience by allowing precise manipulation of neural circuits with light [1-5]. However, a central difficulty has been to deliver spatially shaped light and record deep within the brain without causing damage or significant heating. Current approaches form the light beam in free space and record the neural activity using fluorescence imaging or separately inserted electrodes [6-9], but attenuation limits optical penetration to around 1 mm of the brain surface [10]. Here, we overcome this challenge with foundry-fabricated implantable silicon neural probes that combine microelectrodes for electrophysiology recordings with nanophotonic circuits that emit light with engineered beam profiles and minimal thermal impact. Our experiments reveal that planar light sheets, emitted by our neural probes, excited more neurons and induced greater firing rate fatigue in layers V and VI of the motor and somatosensory cortex of Thy1-ChR2 mice at lower output intensities than low divergence beams. In the hippocampus of an epilepsy mouse model, we induced seizures, a network-wide response, with light sheets without exceeding the[~] 1{whitebullet}C limit for thermally induced electrophysiological responses [11-13]. These findings show that optical spatial profiles can be tailored for optogenetic stimulation paradigms and that the probes can photostimulate and record neural activity at single or population levels while minimizing thermal damage to brain tissue. The neural probes, made in a commercial silicon photonics foundry on 200-mm silicon wafers, demonstrate the manufacturability of the technology. The prospect of monolithically integrating additional well-established silicon photonics devices, such as wavelength and polarization multiplexers, temperature sensors, and optical power monitors, into the probes holds the potential of realizing more versatile, implantable tools for multimodal brain activity mapping.

bioengineering↗

bioRxiv2020

Epigenetic Interaction between UTX and DNMT1 Regulates Diet-Induced Myogenic Remodeling in Brown Fat

Brown adipocytes share the same developmental origin with skeletal muscle. Here we find that a brown adipocyte-to-myocyte remodeling also exists in mature brown adipocytes, and is induced by prolonged high fat diet (HFD) feeding, leading to brown fat dysfunction. This process is regulated by the interaction of epigenetic pathways involving histone and DNA methylation. In mature brown adipocytes, the histone demethylase UTX maintains persistent demethylation of the repressive mark H3K27me3 at Prdm16 promoter, leading to high Prdm16 expression. PRDM16 then recruits DNA methyltransferase DNMT1 to Myod1 promoter, causing Myod1 promoter hypermethylation and suppressing its expression. The interaction between PRDM16 and DNMT1 coordinately serves to maintain brown adipocyte identity while repressing myogenic remodeling in mature brown adipocytes, thus promoting their active brown adipocyte thermogenic function. Suppressing this interaction by HFD feeding induces brown adipocyte-to-myocyte remodeling, which limits brown adipocyte thermogenic capacity and compromises diet-induced thermogenesis, leading to the development of obesity.

physiology↗