Biology subjects

Crickmore, M. A.

Publications and source records attributed to Crickmore, M. A..

5 recordsLinked to original sources

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↗

bioRxiv2020

Biochemical computation underlying behavioral decision-making

Computations in the brain are broadly assumed to emerge from patterns of fast electrical activity. Challenging this view, we show that a male flys decision to persist in mating, even through a potentially lethal threat, hinges on biochemical computations that enable processing over minutes to hours. Each neuron in a recurrent network measuring time into mating contains slightly different internal molecular estimates of elapsed time. Protein Kinase A (PKA) activity contrasts this internal measurement with input from the other neurons to represent evidence that the networks goal has been achieved. When consensus is reached, PKA pushes the network toward a large-scale and synchronized burst of calcium influx, which we call an eruption. The eruption functions like an action potential at the level of the network, transforming deliberation within the network into an all-or-nothing output, after which the male will no longer sacrifice his life to continue mating. We detail the continuous transformation between interwoven molecular and electrical information over long timescales in this system, showing how biochemical activity, invisible to most large scale recording techniques, is the key computational currency directing a life-or-death decision.

neuroscience↗

bioRxiv2020

Behavioural choice emerges from nonlinear all-to-all interactions between drives

Under the right conditions any drive can overcome nearly any other, yet studies of behavioural selection predominantly focus on only one, or occasionally two behaviours. We present an experimental and computational framework that captures and explains the resolution of conflicts between several competing motivations. We characterize neurons that integrate information from all rival drives to generate an aggregate signal that urges male Drosophila to transition out of mating. Experimental investigation of these Drive Integrating Neurons (DINs) revealed time-varying, supralinear interactions among competing drives that stimulate the DINs and induce a change in behaviour. Extending these findings to model the interactions between all of an animals motivations led to the surprising prediction that, under many conditions, all-to-all interactions actually buffer the dominant drive against challengers. We experimentally validated this prediction, showing that weak drives for a variety of tertiary goals can have a profound stabilizing effect on the ongoing behaviour. These results emerge only if non-linear integration of other motivations occurs for each of an animals drives, suggesting the potential universality of this mechanism. Our findings emphasize the interconnectedness of motivational systems and the consequent importance of considering the full motivational state of an animal to understand its behaviour.

neuroscience↗

bioRxiv2019

Hormonal control of motivational circuitry orchestrates the transition to sexuality in Drosophila

Newborns and hatchlings of many species perform incredibly sophisticated behaviors, but all vertebrates and many invertebrates selectively abstain from sexual activity at the beginning of life. Hormonal changes have long been associated with adolescence, but it is not clear how these circulating factors create a new motivation and drive its associated behaviors. We show that the transition to sexuality in male Drosophila is controlled by juvenile hormone, which spikes at eclosion and declines over days as the propensity for courtship gradually increases. Juvenile hormone directly inhibits the activity of at least three courtship-motivating circuit elements, ensuring the complete suppression of sexual motivation and behavior. Blocking or overriding these inhibitory mechanisms evokes immediate and robust sexual behavior from very young and otherwise asexual males. These results provide a first example of hormonal changes gating the transition to sexuality by activating latent, but largely developed and functional, motivational circuitry.

neuroscience↗