HDAC1 NEGATIVELY REGULATES BDNF TRANSCRIPTION & PARVALBUMIN INTERNEURON MATURATION IN AN EXPERIENCE-DEPENDENT MODEL OF THE MOUSE BARREL CORTEX

Abstract

DURING EARLY POSTNATAL DEVELOPMENT, NEURONAL CIRCUITS ARE SCULPTED BY SENSORY EXPERIENCE PROVIDED BY THE EXTERNAL ENVIRONMENT. THIS EXPERIENCE-DEPENDENT REGULATION OF CIRCUITRY DEVELOPMENT CONSOLIDATES THE BALANCE OF EXCITATORY-INHIBITORY (E/I) NEURONS IN THE BRAIN. THE CORTICAL BARREL-COLUMN (S1) THAT INNERVATES A SINGLE PRINCIPAL WHISKER IS USED TO PROVIDE A CLEAR REFERENCE FRAME FOR STUDYING THE CONSOLIDATION OF E/I CIRCUITRY. IT IS KNOWN THAT SENSORY DEPRIVATION OF S1 AT BIRTH DISRUPTS THE CONSOLIDATION OF E/I BALANCE BY DECREASING INHIBITORY TRANSMISSION AT LAYER II/III PARVALBUMIN INTERNEURONS TO PYRAMIDAL NEURONS. THE MOLECULAR MECHANISMS UNDERLYING THIS DECREASE IN INHIBITION ARE INCOMPLETELY UNDERSTOOD. THE OBJECTIVE IN THIS THESIS WAS TO ELUCIDATE MOLECULAR MECHANISMS UNDERLYING THE ESTABLISHMENT OF E/I BALANCE. MY FINDINGS SHOWED THAT EPIGENETIC MECHANISMS, IN PARTICULAR HISTONE DEACETYLATION BY HISTONE DEACETYLASES (HDACS), REGULATED THE EXPRESSION OF BRAIN-DERIVED NEUROTRO