Biology subjects

Samanta, A.

Publications and source records attributed to Samanta, A..

22 records · Page 2Linked to original sources

bioRxiv2019

The Object Space Task reveals a dissociation between semantic-like and episodic-like memory in a mouse model of Kleefstra Syndrome

Kleefstra syndrome is a disorder caused by a mutation in the EHMT1 gene characterized in humans by general developmental delay, mild to severe intellectual disability and autism. Here, we characterized semantic- and episodic-like memory in the Ehmt1+/- mouse model using the Object Space Task. We combined conventional behavioral analysis with automated analysis by deep-learning networks, a session-based computational learning model and a trial-based classifier. Ehmt1 +/- mice showed more anxiety-like features and generally explored objects less, but the difference decreased over time. Interestingly, when analyzing memory-specific exploration, Ehmt1 +/- show increased expression of semantic-like memory, but a deficit in episodic-like memory. A similar dissociation of semantic and episodic memory performance has been previously reported in humans with autism. Using our automatic classifier to differentiate between genotypes, we found that semantic-like memory features are better suited for classification than general exploration differences. Thus, detailed behavioral classification with the Object Space Task produced a more detailed behavioral phenotype of the Ehmt1 +/- mouse model.\n\nOne Sentence SummaryEhmt1 +/- mice show decreased exploration and episodic-like memory but increased semantic-like memory In the Object Space Task. (143 of 150)

neuroscience↗

bioRxiv2019

Molecular mechanism of TRPV2 channel modulation by cannabidiol

Transient receptor potential vanilloid 2 (TRPV2) plays a critical role in neuronal development, cardiac function, immunity, and cancer. Cannabidiol (CBD), the non-psychotropic therapeutically active ingredient of Cannabis sativa, is a potent activator of TRPV2 and also modulates other transient receptor potential (TRP) channels. Here, we determined structures of the full-length TRPV2 channel in a CBD-bound state in detergent and in PI(4,5)P2 enriched nanodiscs by cryo-electron microscopy. CBD interacts with TRPV2 through a hydrophobic pocket located between S5 and S6 helices of adjacent subunits, which differs from known ligand and lipid binding sites in other TRP channels. Comparison between apo- and two CBD-bound TRPV2 structures reveals that the S4-S5 linker plays a critical role in channel gating upon CBD binding. The TRPV2 \"vanilloid\" pocket, which is critical for ligand-dependent gating in other TRPV channels, stays unoccupied by annular lipids, PI(4,5)P2, or CBD. Together these results provide a foundation to further understand TRPV channel gating properties and their divergent physiological functions and to accelerate structure-based drug design.

biophysics↗

bioRxiv2018

The Hex-Maze: A previous knowledge task for mice

New information is rarely learned in isolation, instead most of what we experience can be incorporated into or uses previous knowledge networks in some form. However, most rodent laboratory tasks assume the animal to be naive with no previous experience influencing the results. Previous knowledge in form of a schema can facilitate knowledge acquisition and accelerate systems consolidation: memories become more rapidly hippocampal independent and instead rely more on the prefrontal cortex. Here, we developed a new spatial navigation task where food locations are learned in a large, gangway maze - the HexMaze. Analysing performance across sessions as well as on specific trials, we can show simple memory effects as well as multiple effects of previous knowledge accelerating both online learning and performance increases over offline periods. Importantly, we are the first to show that schema build-up is dependent on how much time passes, not how often the animal is trained.

animal behavior and cognition↗

bioRxiv2018

Structural insights on TRPV5 gating by endogenous modulators

TRPV5 is a transient receptor potential channel involved in calcium reabsorption. Here we investigate the interaction of two endogenous modulators with TRPV5. Both phosphatidylinositol 4,5-bisphosphate (PI(4,5)P2) and calmodulin (CaM) have been shown to directly bind to TRPV5 and activate or inactivate the channel, respectively. Using cryo-electron microscopy (cryo-EM), we determined TRPV5 structures in the presence of dioctanoyl PI(4,5)P2 and CaM. The PI(4,5)P2 structure revealed a novel binding site between the N-linker, S4-S5 linker and S6 helix of TRPV5. These interactions with PI(4,5)P2 induce conformational rearrangements in the lower gate, opening the channel. The CaM structure revealed two TRPV5 C-terminal peptides anchoring a single CaM molecule and that calcium inhibition is mediated through a cation-{pi} interaction between Lys116 on the C-lobe of calcium-activated CaM and Trp583 at the intracellular gate of TRPV5. Overall, this investigation provides insight into the endogenous modulation of TRPV5, which has the potential to guide drug discovery.

biophysics↗