Biology subjects

Sharifi, K.

Publications and source records attributed to Sharifi, K..

3 recordsLinked to original sources

bioRxiv2024

Spatially Enhanced Processing for Valuable Objects in Prefrontal Cortex Neurons During Efficient Search

It is recently shown that objects with long-term reward associations can be efficiently located during visual search. The neural mechanism for valuable object pop-out is unknown. In this work, we recorded neuronal responses in the ventrolateral prefrontal cortex (vlPFC) with known roles in visual search and reward processing in macaques while monkeys engaged in efficient vs inefficient visual search for high-value fractal objects (targets). Behavioral results and modeling using multi-alternative attention-modulated drift-diffusion (MADD) indicated that efficient search was concurrent with enhanced processing for peripheral objects. Notably, neural results showed response amplification and receptive field widening to peripherally presented targets in vlPFC during visual search. Both neural effects predict higher target detection and were found to be correlated with it. Our results suggest that value-driven efficient search independent of low-level visual features arises from reward-induced spatial processing enhancement of peripheral valuable objects.

neuroscience↗

bioRxiv2023

Cortical and subcortical substrates of minutes and days-long object value memory in humans

Obtaining valuable objects motivates many of our daily decisions. However, the neural underpinnings of object processing based on human value memory are not yet fully understood. Here, we used whole-brain fMRI to examine activations due to value memory as participants passively viewed objects before, minutes after, and 1-70 days following value training. Significant value memory for objects was evident in the behavioral performance, which nevertheless faded over the days following training. Minutes after training, the occipital, ventral temporal, interparietal, and frontal areas showed strong value discrimination. Days after training, activation in the frontal, temporal, and occipital regions decreased, whereas the parietal areas showed sustained activation. In addition, days-long value responses emerged in certain subcortical regions, including the caudate, ventral striatum, and thalamus. Resting-state analysis revealed that these subcortical areas were functionally connected. Furthermore, the activation in the thalamo-striatal cluster was positively correlated with participants performance in days-long value memory. These findings shed light on the neural basis of value memory in humans with implications for object habit formation and cross-species comparisons.

neuroscience↗

bioRxiv2020

The Cryo-EM structure of AAV2 Rep68 in complex with ssDNA reveals a malleable AAA+ machine that can switch between oligomeric states.

The adeno-associated virus (AAV) Rep proteins use a unique AAA+ domain to catalyze DNA replication, transcription regulation, and genome packaging. Also, they mediate site-specific integration during a latent phase. To understand the mechanisms underlying AAV Rep function, we investigated the cryo-EM and X-ray structures of Rep68-ssDNA complexes. Surprisingly, Rep68 generates hybrid ring structures where the Origin-Binding-Domain (OBD) forms octameric rings while the helicase domain (HD) forms heptamers. Moreover, the binding to ATP{gamma}S promotes a large conformational change in the entire AAA+ domain that leads the HD to form both heptamer and hexamers. The HD oligomerization is driven by an interdomain linker region that acts as a latch to catch the neighboring HD subunit and is flexible enough to permit the formation of different stoichiometric ring structures. Overall, our studies show the structural basis of AAV Reps structural flexibility required to fulfill its multifunctional role during the AAV life cycle.

biochemistry↗