Application of advanced imaging technology for cell-type specific neural, neuromodulatory and astrocytic signalling in vivo
March 24, 2026 @ 15:00 – 16:00 CET
Sofie Ährlund-Richter, The Picower Institute for Learning and Memory, Massachusetts Institute of Technology (MIT)
Title: Prefrontal Cortex Feedback Reshapes the Representation and Routing of Visual Information
How does the brain determine which sensory signals are behaviorally relevant, and how are these signals routed across cortical networks? Top-down feedback from the prefrontal cortex (PFC) has long been proposed to play a central role in shaping sensory processing, yet the circuit-level mechanisms by which distinct prefrontal pathways modulate sensory representations remain poorly understood.
Here we investigate how anatomically and functionally distinct prefrontal subregions influence visual processing in primary visual cortex (VISp). Using a combination of axonal tracing, two- photon calcium imaging, and projection-specific chemogenetic perturbations in behaving mice, we show that inputs from the anterior cingulate cortex (ACA) and orbitofrontal cortex (ORB) exert dissociable and context-dependent effects on visual responses. Our findings demonstrate that prefrontal feedback is not a uniform gain signal but instead operates through modular pathways that differentially shape sensory representations according to internal state and behavioral context. Building on these results, we are developing next-generation in vivo approaches to uncover the cell-type-specific logic underlying cortical communication. By combining spectral unmixing–based two-photon imaging, projection-defined labeling, and targeted perturbations, we can simultaneously image multiple, defined VISp neuron populations distinguished by their long-range outputs. This strategy enables direct observation of how prefrontal feedback redistributes visual information across parallel cortical output channels in real time.
Together, this work reveals how top-down control dynamically restructures sensory representations and routing in the cortex. By defining circuit principles of prefrontal modulation, these findings provide a framework for understanding how disruptions in feedback control may contribute to altered perception and cognition in neurodevelopmental disorders.
Talk 2:
Iakovos Lazaridis, McGovern Institute for Brain Research, Massachusetts Institute of Technology (MIT)
Title: Striosomes and astrocytes shape striatal dopamine during behavioral state transitions
Abstract: Basal ganglia circuits, modulated by striatal dopamine, support reinforcement learning, action selection, and behavioral flexibility. Integrating two independent lines of evidence, we propose a framework in which striosomes set nigrostriatal output while dorsal striatal astrocytes gate local dopamine availability during behavioral state transitions. Using projection-defined circuit mapping and perturbations, we show that striosomal D1 spiny projection neurons (SPNs) project directly to the substantia nigra pars compacta (SNpc), whereas striosomal D2 SPNs route indirectly via a central external globus pallidus node, forming opponent pathways whose net influence on dopamine differs from matrix circuits. Astrocytes exhibit Ca²⁺ transients time-locked to SNpc-evoked dopamine release, and selective astrocyte activation reduces subsequent dopamine availability without affecting spontaneous locomotion. In a probabilistic decision task, large astrocytic Ca²⁺ events are enriched during disengagement and precede re-engagement; astrocyte signals predict upcoming state transitions and engagement more strongly than trial outcomes, consistent with state-level regulation rather than action coding. Dopamine-dependent astrocytic adenosine release may provide a local mechanism for regulating dopamine availability while biasing D1/D2 signaling, enabling flexible rebalancing of striatal output across behavioral states. Together, these results link striosomal compartmental architecture to motivational control and reveal a glial gate on dopamine dynamics.
Host: Iskra Pollak Dorocic
Google Calendar 
