Biology subjects

Azadi, R.

Publications and source records attributed to Azadi, R..

8 recordsLinked to original sources

bioRxiv2026

A fiducial-based framework for precise MRI-guided stereotaxic targeting in nonhuman primates

Background Accurate MRI-guided stereotaxic targeting in nonhuman primates requires reliable registration between MRI coordinates and stereotaxic space. We evaluated skull-fixed MR-compatible screw fiducials as a practical reference for this registration. Results Using a 3D-printed skull model with 28 fiducials and three internal targets, we compared offset translation, rigid registration, and affine registration under aligned and misaligned conditions. Offset translation was most sensitive to misalignment. Affine registration fit skull-surface fiducials closely, but rigid registration produced lower overall target errors. In vivo validation showed that implanted fiducials could be identified on MRI and re-measured during a later surgery. Comparison with existing methods This approach builds on previous fiducial-based stereotaxic methods by systematically comparing registration transforms, testing misalignment, evaluating fiducial number, and measuring accuracy at independent internal targets. Conclusions Skull-fixed fiducials provide a practical framework for MRI-to-stereotaxic registration. Rigid registration may offer the safest balance between correcting positioning differences and preserving accuracy at internal targets.

neuroscience↗

bioRxiv2025

Discrete interneuron subsets participate in GluN1/GluN3A excitatory glycine receptor (eGlyR)-mediated regulation of hippocampal network activity throughout development and evolution.

Decades of studies implicating GluN3A N-methyl-D-aspartate receptor (NMDAR) subunits in physiological and pathological function have largely been interpreted through direct regulation of conventional glutamatergic NMDARs. However, emerging evidence indicates that GluN3A frequently assembles with GluN1 forming unconventional glutamate-insensitive NMDARs that operate as native excitatory glycine receptors (eGlyRs). Here we demonstrate that hippocampal somatostatin and neurogliaform interneurons (Sst-INs and NGFCs) express functional eGlyRs from early postnatal through adult ages. In the developing hippocampus eGlyR-mediated excitation of NGFCs with ambient glycine dramatically increases GABAergic tone, with consequences for the generation of giant depolarizing potentials (GDPs). In the mature hippocampus, eGlyR- mediated excitation of Sst-INs regulates sharp wave ripples (SWRs). Finally, we reveal evolutionary conservation of hippocampal Sst-IN eGlyRs and eGlyR- mediated SWR regulation in non-human primates confirming functional eGlyR availability for therapeutic potential in higher species. Our findings underscore that eGlyR mediated regulation of cell and circuit excitability through both cell autonomous and cell non-autonomous mechanisms must be considered to understand GluN3A roles in brain development, plasticity, and disease.

neuroscience↗

bioRxiv2024

An enhancer-AAV toolbox to target and manipulate distinct interneuron subtypes

In recent years, we and others have identified a number of enhancers that, when incorporated into rAAV vectors, can restrict the transgene expression to particular neuronal populations. Yet, viral tools to access and manipulate specific neuronal subtypes are still limited. Here, we performed systematic analysis of single cell genomic data to identify enhancer candidates for each of the telencephalic interneuron subtypes. We established a set of enhancer-AAV tools that are highly specific for distinct cortical interneuron populations and striatal cholinergic interneurons. These enhancers, when used in the context of different effectors, can target (fluorescent proteins), observe activity (GCaMP) and manipulate (opto-genetics) specific neuronal subtypes. We also validated our enhancer-AAV tools across species. Thus, we provide the field with a powerful set of tools to study neural circuits and functions and to develop precise and targeted therapy.

neuroscience↗

bioRxiv2024

3D-Printable Non-invasive Head Immobilization System for Non-Human Primates

A critical contribution to understanding the primate brain is our ability to directly record, manipulate, or image the brain in awake, behaving monkeys. A challenge with carrying out these studies is that typically the monkeys head must be fixed in place. While non-invasive head immobilization systems (NHIS) have been demonstrated to be effective, they have not fully replaced the use of surgically applied headposts. Here, we introduce a novel NHIS, with an option for voluntary engagement, for macaques using a widely available resource: the 3D printer. We designed customized 3D-printable head-immobilization masks for monkeys and a docking system using standard CT scans and user-friendly open-source software packages (FLoRIN, Blender, Python). We examined the efficacy and stability of our mask system for collecting eye fixation data by measuring trial-by-trial gaze precision and accuracy in two mask-immobilized monkeys and three headposted monkeys, including a within-subjects comparison. Our results demonstrate that monkeys stabilized by the mask maintain gaze precision and accuracy comparable with their headposted counterparts. While the headpost outperformed the mask, the difference in precision was 0.03{degrees} of visual angle, and the difference in accuracy was less than 0.2{degrees}, well within the acceptable range for most use-cases. Our process allows for the production of 3D-printable masks based on CT or MRI scans with the flexibility to incorporate design modifications for experimental equipment and resizing, potentially serving as a promising and more easily accessible alternative to headposts and other NHISs for primate neuroscience research.

physiology↗

bioRxiv2023

Inactivation of face selective neurons alters eye movements when free viewing faces

During free viewing, faces attract gaze and induce specific fixation patterns corresponding to the facial features. This suggests that neurons encoding the facial features are in the causal chain that steers the eyes. However, there is no physiological evidence to support a mechanistic link between face encoding neurons in high-level visual areas and the oculomotor system. In this study, we targeted the middle face patches of inferior temporal (IT) cortex in two macaque monkeys using an fMRI localizer. We then utilized muscimol microinjection to unilaterally suppress IT neural activity inside and outside the face patches and recorded eye movements while the animals free viewing natural scenes. Inactivation of the face selective neurons altered the pattern of eye movements on faces: the monkeys found faces in the scene but neglected the eye contralateral to the inactivation hemisphere. These findings reveal the causal contribution of the high-level visual cortex in eye movements. SignificanceIt has been shown, for more than half a century, that eye movements follow distinctive patterns when free viewing faces. This suggests causal involvement of the face-encoding visual neurons in the eye movements. However, the literature is scant of evidence for this possibility and has focused mostly on the link between low-level image saliency and eye movements. Here, for the first time, we bring causal evidence showing how face-selective neurons in inferior temporal cortex inform and steer eye movements when free viewing faces.

neuroscience↗

bioRxiv2022

Behavioral detectability of optogenetic stimulation of inferior temporal cortex varies with the size of concurrently viewed objects.

We have previously demonstrated that macaque monkeys can behaviorally detect a subtle optogenetic impulse delivered to their inferior temporal (IT) cortex. We have also shown that the ability to detect the cortical stimulation impulse varies depending on some characteristics of the visual images viewed at the time of brain stimulation, revealing the visual nature of the perceptual events induced by stimulation of the IT cortex. Here we systematically studied the effect of the size of viewed objects on behavioral detectability of optogenetic stimulation of the central IT cortex. Surprisingly, we found that behavioral detection of the same optogenetic impulse highly varies with the size of the viewed object images. Reduction of the object size in four steps from 8 to 1 degree of visual angle significantly decreased detection performance. These results show that identical stimulation impulses delivered to the same neural population induce variable perceptual events depending on the mere size of the objects viewed at the time of brain stimulation.

neuroscience↗

bioRxiv2022

Surgical procedure for implantation of Opto-Array in nonhuman primates

Optogenetics allows precise temporal control of neuronal activity in the brain. Engineered viral vectors are routinely used to transduce neurons with light-sensitive opsins. However, reliable virus injection and light delivery in animals with large brains, such as nonhuman primates, has proven challenging. The Opto-Array is a novel yet simple device that is used to deliver light to extended regions of surface cortex for high-throughput behavioral optogenetics in large brains. Here we present protocols for surgical delivery of virus and implantation of the Opto-Array in two separate surgeries in a rhesus monkeys inferior temporal cortex. As a proof of concept, we measured the behavioral performance of an animal detecting cortical optogenetic stimulations with different illumination power and duration using the Opto-Array. The animal was able to detect the optogenetic stimulation for all tested illumination powers and durations. A regression analysis also showed both power and duration of illumination significantly modulate the detectability of the optogenetic stimulation. The outcome of this approach is superior to the standard practice of injecting and recording through a chamber for large areas of surface cortex. Moreover, the chronic nature of the Opto-Array allows perturbation of neuronal activity of the same site across multiple sessions because it is highly stable, thus data can be pooled over months. The detailed surgical method presented here makes it possible to use optogenetics to modulate neuronal activity across large regions of surface cortex in the nonhuman primate brain.

neuroscience↗

bioRxiv2020

Chronically implantable LED arrays for behavioral optogenetics in primates.

Challenges in behavioral optogenetics in large brains demand development of a chronically implantable platform for light delivery. We have developed Opto-Array, a chronically implantable array of LEDs for high-throughput optogenetic perturbation in non-human primates. We tested the Opto-Array in the primary visual cortex of a macaque monkey, and demonstrated that optogenetic cortical silencing by the Opto-Array results in reliable retinotopic visual deficits on a luminance discrimination task.

neuroscience↗