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Kirsch, A.

Publications and source records attributed to Kirsch, A..

2 recordsLinked to original sources

Intrinsic Goals for Autonomous Agents: Hierarchical Exploration Captures Future Volitional Action in Drosophila

Animals have a remarkable ability to act autonomously---driven by intrinsic motivation---without external sensory cues or extrinsic objectives, yet the computational mechanisms behind this ability largely remain a mystery. To understand how biological autonomy may emerge from optimizing intrinsic goals, we use recent whole-brain recordings in the fruit fly (\textit{Drosophila melanogaster}) that identify neural representations of spontaneous exploratory decisions more than $10$ seconds in advance. Combined with a neuromechanical digital twin of \textit{Drosophila}, these recordings allow us to test whether intrinsically motivated artificial agents with realistic embodiments quantitatively match fly behavior and internal representations of future volitional action during exploration. We implement a hierarchical, intrinsically motivated agent whose policy operates over a discrete library of motor primitives---fixed low-level controllers that actuate joint dynamics---closely matching ethological theories of behavioral syllables. We train agents with no external reward using $20$ intrinsic motivation algorithms spanning curiosity, entropy, and competency methods. We evaluate frozen policies in a virtual tethered-ball assay modeled after the fruit-fly experiment, allowing us to compare spontaneous locomotor statistics and internal representations and decode future turn direction from both kinematics and neural activations on the same timescales observed in flies. We find that DIAYN---a hierarchical competency algorithm that learns a discrete set of policies maximizing behavioral entropy and the separability of their induced sensory observations---achieves the strongest joint behavioral and neural prospective coding performance with the fruit fly. Surprisingly, DIAYN's learned policies closely capture individual variability in fly exploration strategies, suggesting that this behavioral diversity optimizes a concrete computational goal of maximizing state-space coverage at the \emph{population} level. Furthermore, DIAYN agents' latent activity closely captures the specific sum-difference rule in interhemispheric encoding of future kinematics in biological flies. Together, these results establish hierarchical, intrinsically motivated agents as a powerful framework for reverse-engineering animal autonomy.

neuroscience↗

beta3-adrenergic browning of pericardial adipose tissue controls cardiac function

Dysfunctional adipose tissue (AT) is strongly linked to the development of cardiovascular diseases (CVD). Accumulation of AT around vital organs is detrimental to their respective function and overall health. Although there is strong evidence linking the accumulation of pericardial AT with CVD development, a comprehensive investigation on the adaptation of pAT in obesity is scarce. Here, by applying pair-wise bottom-up proteomics in pAT of humans and mice, we found pAT presents a browning signature, as demonstrated by enrichment of mitochondria, presence of UCP1, and greater metabolic capacity compared to subcutaneous AT. In mice fed a high-fat diet or obese patients, the pAT undergoes whitening, characterized by adipocyte hypertrophy, reduced mitochondrial content, respiratory capacity, and UCP1 levels. Lipectomy of pAT from obese mice decreased pathological ventricular hypertrophy. Conversely, selective {beta}3-adrenergic agonist treatment rescued pAT browning status and is associated with improved heart structure and function, including ventricular thickness, and fibrosis in obese mice. Importantly, lipectomy of pAT abrogated the positive effects of {beta}3-adrenergic agonism in cardiac function of obese mice. Altogether, our work positions pAT as a mechanistic driver of obesity-related cardiac dysfunction and establish {beta}3-adrenergic-mediated browning of pAT as a novel therapeutic treatment strategy.

physiology↗