Our research has been centered around the following three questions:
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 and 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 and Asari, PLoS One 2022). These results showcase a power of combining theory and experiments to obtain mechanistic understandings of neural information processing.
2. What does the eye tell the brain in vivo under different behavioral contexts?
Retinal signaling has been well studied ex vivo (e.g., Asari and Meister, Nat Neurosci 2012; Asari and Meister, 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 pharmacological and chemogenetic tools, we subsequently revealed that reduced histaminergic signaling in mice – as is observed when animals are dormant – leads to a significant facilitation of the visual response gain and kinetics in the retina (Tripodi and Asari, PLoS Biol 2025).
Using in vivo two-photon axonal imaging, we also functionally mapped how retinal axons project to the superior colliculus, and revealed precise retinotopic organizations at a single-cell resolution (Molotkov, Ferrarese, et al., Nat Commun 2023). This highlights the 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 disease 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 and 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.
Future projects and goals
Based on the results we obtained in the past years, we will extend our current research program to characterize how an animal’s behavior and internal states affect retinal visual processing, and how such changes in retinal computation affect visual representations in the downstream areas. Everything that the brain sees depends on the retina. Thus, to better understand how our visual percept arises under different behavioral contexts, it is indispensable to characterize retinal signals as an integrated part of the entire nervous system, but not in isolation. The retina shares many common features with the rest of the brain, such as diverse cell types and neuromodulations. Our study will then provide key insights into not only early visual processing, but also how networks and physiological properties of neurons are combined to perform complex and adaptive computations.
We will also continue to analyze disease model mice in our experimental paradigm. We envision that systems neuroscience approach to sensory dysfunction is a promising future direction to find a link between genetic, behavioral, and neurophysiological phenotypes.