Project Grant F31DC022802

THE ROLE OF MOUSE AUDITORY CORTEX AND INFERIOR COLLICULUS IN RECOVERY FROM HEARING LOSS - THE ABILITY TO LOCALIZE SOUND IS VITAL FOR COMMUNICATING WITH OTHER PEOPLE. SOUND LOCALIZATION USUALLY DEPENDS ON INPUT FROM BOTH EARS, AND SO IT IS ESPECIALLY IMPAIRED BY UNILATERAL HEARING LOSS, WHICH IS CAUSED BY COMMON CONDITIONS LIKE EAR INFECTION. THE BRAIN CAN COMPENSATE BY RE-INTERPRETING CUES FROM THE DAMAGED EAR OR FAVORING INPUT FROM THE INTACT EAR. THESE NEURAL MECHANISMS OF RECOVERY ARE INCOMPLETELY UNDERSTOOD BUT THE PROJECTION FROM AUDITORY CORTEX FROM INFERIOR COLLICULUS HAS BEEN SHOWN TO BE NECESSARY FOR SPATIAL HEARING AFTER HEARING LOSS. HOWEVER, THESE STUDIES HAVE NOT EXAMINED THE ELECTROPHYSIOLOGICAL CHANGES THAT OCCUR AFTER HEARING LOSS. THEREFORE, THE EXACT ROLE OF THE SIGNALS BEING SENT FROM AUDITORY CORTEX TO INFERIOR COLLICULUS AFTER HEARING LOSS ARE NOT YET UNDERSTOOD. TO ANSWER THIS QUESTION, MY SPONSOR'S LAB HAS DEVELOPED A SPATIAL HEARING BEHAVIOR PARADIGM IN WHICH MICE MUST LOCATE SOUND. MICE WITH UNILATERAL HEARING LOSS ARE INITIALLY IMPAIRED AT THIS TASK BUT SHOW ROBUST RECOVERY. USING THIS PARADIGM, I WILL RECORD IN AUDITORY CORTEX AND INFERIOR COLLICULUS OF MICE OVER THE COURSE OF BEHAVIORAL RECOVERY TO DETERMINE HOW CHANGES IN NEURAL ACTIVITY DRIVE CHANGES IN BEHAVIOR. MY CENTRAL HYPOTHESIS IS THAT AFTER HEARING LOSS, AUDITORY CORTEX DRIVES RECOVERY OF SPATIAL TUNING IN INFERIOR COLLICULUS NEURONS, ALLOWING RECOVERY OF SPATIAL HEARING DESPITE DEGRADED INFORMATION FROM THE PERIPHERY. THE GOAL OF THIS PROJECT IS TO DETERMINE HOW SPATIAL TUNING OF CORTICAL AND COLLICULAR NEURONS ENABLE BEHAVIORAL RECOVERY, WHICH I WILL ADDRESS THROUGH TWO AIMS. AIM 1 IS TO DETERMINE HOW AUDITORY CORTEX AND INFERIOR COLLICULUS RECOVER SPATIAL TUNING AFTER HEARING LOSS, WHICH I WILL ACHIEVE THROUGH CHRONIC ELECTROPHYSIOLOGICAL RECORDING IN THESE REGIONS BEFORE AND DURING RECOVERY FROM HEARING LOSS AND BY COMPARING BETWEEN MICE PERFORMING THE BEHAVIOR TASK VERSUS ANIMALS PASSIVELY LISTENING TO SOUND. AIM 2 IS TO DETERMINE THE CAUSAL ROLE OF AUDITORY CORTEX IN RECOVERY FROM HEARING LOSS, IN WHICH I WILL USE CHEMOGENETIC MANIPULATIONS TO SUPPRESS AUDITORY CORTEX ACTIVITY AND TO DETERMINE THE EFFECTS ON INFERIOR COLLICULUS SPATIAL TUNING. THIS PROJECT WILL ELUCIDATE THE NEURAL CHANGES THAT ENABLE RECOVERY AFTER SENSORY LOSS IN FREELY MOVING MICE. ULTIMATELY, THIS RESEARCH WILL ALLOW US TO DEVELOP TREATMENTS FOR HEARING LOSS THAT LEVERAGE THE BRAIN'S PLASTICITY. MOREOVER, THIS FELLOWSHIP WILL PROVIDE ME WITH CRUCIAL TRAINING IN AUDITORY NEUROSCIENCE AND ANIMAL BEHAVIOR FROM MY SPONSOR DR. CHRIS RODGERS AND MY CO-SPONSOR DR. ROBERT LIU. I WILL HAVE SUPPORT FROM THE BROAD COMMUNITY OF SYSTEMS NEUROSCIENTISTS AT EMORY, INCLUDING DR. MALAVIKA MURUGAN WHO WRITES A LETTER OF SUPPORT. THIS TRAINING WILL PREPARE ME FOR POSTDOCTORAL RESEARCH AND TO BECOME AN INDEPENDENT INVESTIGATOR.