Biology subjects

Akolkar, H.

Publications and source records attributed to Akolkar, H..

3 recordsLinked to original sources

bioRxiv2025

APP overexpression delays synaptic development and alters neuronal network properties

The amyloid precursor protein (APP) regulates neuronal excitability by altering the structure of the axon initial segment. Using high density multielectrode arrays we compared the electrophysiological consequences of APP overexpression with exposure to {beta}-amyloid (A{beta}) and found that the two manipulations affected neural activity in largely non-overlapping ways. In mature cultures (>18 days in vitro, DIV18), APP reduced the firing probability of individual neurons, while {beta}-amyloid stripped synapses impacting whole-network connectivity. In immature cultures (DIV10), increasing APP - either acutely with lentiviral vectors or genetically by culturing APP transgenic neurons - revealed a separate developmental function. Synaptogenesis and axonal branch formation were blocked. A{beta}, by contrast, interfered primarily with network behavior. Our findings suggest that Alzheimers disease is likely an amalgamation of APP mis-regulation plus the effects of A{beta} accumulation. They also urge consideration of the idea that familial and sporadic forms of Alzheimers may represent distinct disease processes.

neuroscience↗

bioRxiv2025

Tuning of Task-Relevant Stiffness in Multiple Directions

The dynamics of any mechanical system can be described in terms of forces and motions. The interaction of these terms is often captured in the metric of mechanical impedance - a generalization of stiffness - used to describe how a mechanical system resists the application of force. The ability to adaptively change impedance is advantageous when encountering variable environmental conditions. Changing impedance in robotic systems is limited, whereas humans can rapidly and elegantly adapt the impedance of their limbs, especially during initial contact with objects. This is especially true for movements of our arms and hands. Multiple studies have examined the arms response to perturbation with the idea of impedance as a reactive component. In this study, we investigate the ability of humans to predictively set their arm impedance in a contact breaking task to perform fast movements to target positions in different directions. Our findings show that subjects (n=20) predictively co-activate antagonist muscles to primarily adjust one component of the arms impedance - stiffness - to match different task constraints before the movement begins irrespective of movement direction. Interestingly, the subjects performance was limited by the task-dependent stiffness rather than the required force and they tended to generate minimal stiffness to perform the task. With this robust strategy, task success is optimized at the expense of energy efficiency. This type of control is essential for the uniquely human ability to interact with objects.

neuroscience↗

bioRxiv2020

Optogenetic therapy: High spatiotemporal resolution and pattern recognition compatible with vision restoration in non-human primates

Restoring vision using optogenetics is an ideal medical application because the eye offers a direct window to access and stimulate the pathological area: the retina. Optogenetic therapy could be applied to diseases with photoreceptor degeneration such as retinitis pigmentosa. Here, we select the specific optogenetic construct that is now used in the clinical trial and assess the opsin functional efficacy on non-human primates retinal ganglion cells (RGCs). We chose the microbial opsin ChrimsonR and showed that the vector AAV2.7m8 produced greater transfection in RGCs compared to AAV2, and that ChrimsonR attached to tdTomato (ChR-tdT) is more efficiently expressed than ChrimsonR. The 600 nm light activates the RGCs transfected with the vector AAV2.7m8-ChR-tdT from an irradiance of 1015 photons.cm-2.s-1. Vector doses of 5.1010 and 5.1011 vg/eye transfect up to 7000 RGCs/mm2 in the perifovea, with no significant immune reaction. Furthermore, using a multielectrode array we recorded RGCs responses starting from 1ms stimulus duration. Using the recorded activity we were able to decode stimulus information and estimate a theoretical visual acuity of 20/249, above legal blindness. Altogether, our results pave the way for the ongoing clinical trial with the AAV2.7m8-ChrimsonR-tdT vector for vision restoration in patients affected by retinitis pigmentosa. One Sentence SummaryWe select here the vector and genetic construct best suited to provide vision restoration in patients suffering from retinopathies, we demonstrate temporal resolution compatible with high dynamic visual scenes and a visual acuity above legal blindness.

neuroscience↗