My group has been pursuing both basic and translational questions of early visual processing using in vivo experimental and computational approaches in the mouse:
1. How does "computation" arise from interactions of neurons?
Neurons form various interconnected circuits to perform diverse computations. We have been taking a theory-driven approach to dissect relationships between structural connectivity and neural dynamics. For example, we developed a biologically plausible – yet computationally tractable – model of the retina, and experimentally validated model predictions on the retinal circuit functions (Real et al., Curr Biol, 2017; Vlasiuk & Asari, PLoS One, 2021). A similar modelling approach was employed to better understand the hypothalamic circuit function underlying mouse innate behavior (Rahy et al., Front Comput Neurosci, 2022). We also analyzed natural image statistics to test the optimality of mouse vision (Abballe & Asari, PLoS One, 2022). These results showcase a power of combining theory and experiments to obtain mechanistic understandings of neuronal information processing.
2. What does the eye tell the brain under different behavioral contexts?
Retinal signaling has been well studied ex vivo (e.g., Asari & Meister, Nat Neurosci, 2012; Neuron, 2014), with an assumption that findings from these studies can be naturally translated to how the retina operates in vivo. Using in vivo optic tract recordings, we directly monitored retinal output in awake mice, and found distinct retinal response properties compared to those in anesthetized or ex vivo conditions (Boissonnet et al., eLife, 2023). This indicates a need to be cautious about that assumption, and led us to further study behavioral modulation of the retinal visual processing. Combining in vivo electrophysiogy with circuit perturbation tools in mice, we recently discoverd that reduced histaminergic signaling – as is observed when animals are less active – facilitates the response dynamics of the retina and the downstream visual pathway (Tripodi & Asari, PLoS Biol, 2025). Thus, adaptive mechanisms to an animal's behavior already exist in the retina, the very first stage of the visual processing.
Using in vivo two-photon axonal imaging, we also functionally mapped how output nerve fibers from the retina are connected to neurons in a target brain area, and revealed precise topographic organizations at a single-cell resolution (Molotkov, Ferrarese, et al., Nat Commun, 2023). This highlights a precision of brain wiring, and raises a possibility that the nervous systems are wired more precisely than previously thought to exploit topographic information for their function.
3. How is visual processing altered in psychiatric conditions?
While an animal’s behavior can modulate visual processing, the visual system in turn can affect behavior by predicting future events based on current sensory information and past experiences. Anomaly in such inference process is thought to underlie various symptoms in psychiatric conditions, and we indeed found sensory expectation mismatch in a mouse model of autism at both neurophysiological and behavioral levels (Ferrarese & Asari, Nat Commun, 2025). Specifically, mice carrying a genetic mutation that causes autism in humans cannot fully exploit past experiences to update visual sensory responses; and this phenotype derives from a deficit in corticotectral feedback in the visual system. These results provide neurophysiological underpinning for atypical learning behavior in autism. We envision that systems neuroscience approach to sensory dysfunction is a promising future direction to find a link between genetic, behavioral, and neurophysiological phenotypes.
