MLRisherLab

Our laboratory investigates how astrocytes regulate synaptic and neural circuit function and how persistent changes in astrocyte state contribute to behavioral dysfunction. A central focus of our work is understanding how peripheral astrocytic process interactions with synapses, intracellular Ca²⁺ signaling, gliotransmission, and mitochondrial and metabolic function interact to regulate neuronal activity and circuit plasticity.

We use a variety of tools to answer these questions, including: super-resolution microscopy, spatial transcriptomics, fiber photometry, viral and chemogenetic approaches, cellular bioenergetics, and behavioral neuroscience, we study astrocyte function across molecular, synaptic, circuit, and behavioral assays (e.g., conditioned place preference, fear conditioning, social interaction, and set-shifting).

Our recent work demonstrates that developmental perturbation can produce persistent remodeling of astrocyte-synaptic interactions are accompanied by altered Ca²⁺ responsivity, homeostatic adaptation, disrupted gliotransmitter signaling, and behavioral dysfunction. Importantly, targeted restoration of astrocyte activity can recover components of downstream signaling and behavioral function, supporting a causal role for astrocytes in regulating circuit-level outcomes.

These findings have led to a broader research direction focused on understanding persistent maladaptive astrocyte states: how they are established and maintained, how they reshape astrocyte-synapse and astrocyte-neuron communication, and what determines their capacity for recovery. Current studies examine mitochondrial bioenergetics and quality control, lipid and redox homeostasis, Ca²⁺ signaling, and molecular mechanisms that may maintain persistent astrocyte dysfunction.

Our long-term goal is to define the mechanisms governing transitions among adaptive, persistent maladaptive, and restored astrocyte states and determine how these transitions influence synaptic organization, neuronal physiology, circuit activity, and behavior. By understanding what makes astrocyte dysfunction persistent, and what makes it reversible, we aim to identify fundamental principles of astrocyte regulation in health and disease and establish astrocytes as therapeutic entry points for restoring dysfunctional neural circuits.

 Projects Include:

- Characterizing structural and functional adolescent tripartite synapse development across the brain

- Understanding the long-term effects of adolescent binge drinking

- Understanding how astrocyte perturbations in adolescence impacts brain recovery after a secondary injury.

- How life-time drinking impacts aging and gut-brain axis

- Identifying and developing novel non-neuronal therapeutic approaches

What We've Achieved