Project Grant F31EY038632

THE ROLE OF ASTROCYTE NEUROMODULATION IN CORTICAL PLASTICITY AND LEARNING - PROJECT SUMMARY ASTROCYTES, ONCE CONSIDERED PASSIVE SUPPORT CELLS IN THE BRAIN, ARE NOW RECOGNIZED AS ACTIVE REGULATORS OF SYNAPTIC FUNCTION AND PLASTICITY. EMERGING EVIDENCE SUGGESTS THAT LARGE-SCALE ASTROCYTIC CALCIUM EVENTS COINCIDE WITH WIDESPREAD NEUROMODULATOR RELEASE THAT CORRELATES WITH BEHAVIORAL MEASURES OF AROUSAL SUCH AS PUPIL DILATION. THE RELEASE OF NEUROMODULATORS IS THOUGHT TO ENHANCE LEARNING EFFICIENCY BY MODULATING HOW SENSORY INFORMATION IS ENCODED. HOWEVER, THE MECHANISMS BY WHICH ASTROCYTIC CALCIUM INFLUENCES SENSORY ENCODING AND LEARNING REMAIN POORLY UNDERSTOOD. THIS PROPOSAL AIMS TO DETERMINE HOW ASTROCYTE CALCIUM ACTIVITY SHAPES LOCAL NEURONAL NETWORK ACTIVITY TO FACILITATE LEARNING. THE PROJECT WILL USE VISUALLY EVOKED EYEBLINK CONDITIONING IN MICE, A BEHAVIOR THAT ENGAGES BOTH THE VISUAL CORTEX AND CEREBELLUM, REGIONS KNOWN FOR PRONOUNCED ASTROCYTE CALCIUM ACTIVITY. IN THE FIRST AIM, I WILL TEST WHETHER MANIPULATING ASTROCYTIC CALCIUM LEVELS IN THE VISUAL CORTEX ALTERS ACQUISITION, DISCRIMINATION, EXTINCTION AND REACQUISITION OF LEARNED ASSOCIATIONS. IN THE SECOND AIM, I WILL USE TWO- PHOTON MICROSCOPY TO IMAGE ASTROCYTES AND NEURONS THROUGHOUT ASSOCIATIVE LEARNING TO INVESTIGATE HOW ASTROCYTIC ACTIVITY CORRELATES WITH AND CAUSALLY INFLUENCES CORTICAL SYNAPTIC PLASTICITY DURING LEARNING. THE FELLOWSHIP TRAINING PLAN EMPHASIZES HANDS-ON EXPERIENCE WITH TWO-PHOTON MICROSCOPY, CHEMOGENETICS, AND BEHAVIORAL ANALYSIS. RESEARCH WILL TAKE PLACE IN A COLLABORATIVE NEUROSCIENCE ENVIRONMENT WITH ACCESS TO ADVANCED OPTICAL AND GENETIC TOOLS. THIS TRAINING WILL PREPARE THE APPLICANT FOR AN INDEPENDENT RESEARCH CAREER FOCUSED ON GLIA-NEURON INTERACTIONS IN SYNAPTIC PLASTICITY AND LEARNING.