Biology subjects

Gautham, A. K.

Publications and source records attributed to Gautham, A. K..

3 recordsLinked to original sources

bioRxiv2024

Retinoic acid breakdown is required for proximodistal positional identity during amphibian limb regeneration

Regenerating limbs retain their proximodistal (PD) positional identity following amputation. This positional identity is genetically encoded by PD patterning genes that instruct blastema cells to regenerate the appropriate PD limb segment. Retinoic acid (RA) is known to specify proximal limb identity, but how RA signaling levels are established in the blastema is unknown. Here, we show that RA breakdown via CYP26B1 is essential for determining RA signaling levels within blastemas. CYP26B1 inhibition molecularly reprograms distal blastemas into a more proximal identity, phenocopying the effects of administering excess RA. We identify Shox as an RA-responsive gene that is differentially expressed between proximally and distally amputated limbs. Ablation of Shox results in shortened limbs with proximal skeletal elements that fail to initiate endochondral ossification. These results suggest that PD positional identity is determined by RA degradation and RA-responsive genes that regulate PD skeletal element formation during limb regeneration.

developmental biology↗

bioRxiv2024

Molecular control of temporal integration matches decision-making to motivational state

Motivations bias our responses to stimuli, producing behavioral outcomes that match our needs and goals. We describe a mechanism behind this phenomenon: adjusting the time over which stimulus-derived information is permitted to accumulate toward a decision. As a Drosophila copulation progresses, the male becomes less likely to continue mating through challenges. We show that a set of Copulation Decision Neurons (CDNs) flexibly integrates information about competing drives to mediate this decision. Early in mating, dopamine signaling restricts CDN integration time by potentiating CaMKII activation in response to stimulatory inputs, imposing a high threshold for changing behaviors. Later into mating, the timescale over which the CDNs integrate termination-promoting information expands, increasing the likelihood of switching behaviors. We suggest scalable windows of temporal integration at dedicated circuit nodes as a key but underappreciated variable in state-based decision-making.

neuroscience↗

bioRxiv2024

Local desensitization to dopamine devalues recurring behavior

Goal achievement adjusts the relative importance of future behaviors. We use Drosophila to study this form of motivational control, finding that prior matings make males increasingly likely to abandon future copulations when challenged. Repetition-induced devaluation results from a reduction in dopamine reception by the Copulation Decision Neurons (CDNs), which mediate the decision to end matings. Dopamine signaling to the CDNs sustains matings in real time, but also triggers a lasting, {beta}-arrestin-dependent desensitization of the D2R on the CDNs, leaving subsequent matings susceptible to disruption. When D2R desensitization is experimentally prevented, the male treats each mating as if it were his first. These findings provide a generalizable mechanism of motivational control and reveal a natural function for the long-studied susceptibility of the D2R to drug-induced inactivation.

neuroscience↗