Organization of thalamic networks and mechanisms of dysfunction in schizophrenia and autism

Thalamic networks, at the core of thalamocortical and thalamosubcortical communications, underlie processes of perception, attention, memory, emotions, and the sleep-wake cycle, and are disrupted in mental disorders, including schizophrenia and autism. However, the underlying mechanisms of pathology are unknown. I will present novel evidence on key organizational principles, structural, and molecular features of thalamocortical networks, as well as critical thalamic pathway interactions that are likely affected in disorders. This data can facilitate modeling typical and abnormal brain function and can provide the foundation to understand heterogeneous disruption of these networks in sleep disorders, attention deficits, and cognitive and affective impairments in schizophrenia and autism, with important implications for the design of targeted therapeutic interventions

Coordinated hippocampal-thalamic-cortical communication crucial for engram dynamics underneath systems consolidation

Astrocytes contribute to remote memory formation by modulating hippocampal-cortical communication during learning

How is it that some memories fade in a day while others last forever? The formation of long-lasting (remote) memories depends on the coordinated activity between the hippocampus and frontal cortices, but the timeline of these interactions is debated. Astrocytes, star-shaped glial cells, sense and modify neuronal activity, but their role in remote memory is scarcely explored. We manipulated the activity of hippocampal astrocytes during memory acquisition and discovered it impaired remote, but not recent, memory retrieval. We also revealed a massive recruitment of cortical-projecting hippocampal neurons during memory acquisition, a process that is specifically inhibited by astrocytic manipulation. Finally, we directly inhibited this projection during memory acquisition to prove its necessity for the formation of remote memory. Our findings reveal that the foundation of remote memory can be established during acquisition with projection-specific effect of astrocytes.

Mechanisms of cortical communication during decision-making

Regulation of information flow in the brain is critical for many forms of behavior. In the process of sensory based decision-making, decisions about future actions are held in memory until enacted, making them potentially vulnerable to distracting sensory input. Therefore, gating of information flow from sensory to motor areas could protect memory from interference during decision-making, but the underlying network mechanisms are not understood. I will present our recent experimental and modeling work describing how information flow from the sensory cortex can be gated by state-dependent frontal cortex dynamics during decision-making in mice. Our results show that communication between brain regions can be regulated via attractor dynamics, which control the degree of commitment to an action, and reveal a novel mechanism of gating of neural information.