Molecular Mechanisms of Synaptic Plasticity in Adult Mammalian Sensory Cortex

Title of Document: MOLECULAR MECHANISMS OF SYNAPTIC PLASTICITY IN ADULT MAMMALIAN SENSORY CORTEX Haiyan He, Doctor of Philosophy, 2007 Directed By: Dr. Elizabeth M Quinlan Department of Biology Experience-dependent changes in synaptic composition and function (synaptic plasticity) underlie many brain functions including learning and memory, formation of sensory maps, as well as the capability to recover from injury. Most of these functions decline with age, supporting the observation that synaptic plasticity is greater in juveniles than in adults. However, it has been known for some time that peripheral deafferentation in adult animals can induce large-scale reorganization of sensory cortex, which suggests that the adult cortex retains a level of synaptic plasticity that is typically masked by normal activity inputs. Here I present a series of experiments in the adult mammalian sensory cortex that examine the mechanisms and methods to enhance experience-dependent synaptic plasticity. The results showed: 1. Peripheral deafferentation of a single digit in the adult raccoon induces progressive modulation of excitation and inhibition in the deafferented somatosensory cortex that might be needed for the reorganization of receptive fields; 2. Visual deprivation in adult rats reverses three molecular mechanisms that have been correlated with the decrease in synaptic plasticity in adult cortex. These include the developmental increase in the level of inhibition relative to excitation, the development switch in NMDA receptor subunit composition from NR2b to NR2a, and the developmental decrease in tPA activity in visual cortex; 3.Visual deprivation rejuvenates ocular dominance plasticity in the adult visual cortex, and promotes the functional recovery of an eye deprived of vision from birth in adulthood. This work provides further understanding of the molecular mechanisms underlying experience-dependent cortical plasticity. In addition, it demonstrates that ocular dominance plasticity can be regulated throughout life, and proposes a non-invasive method to enhance synaptic plasticity in adult cortex. MOLECULAR MECHANISMS OF SYNAPTIC PLASTICITY IN ADULT MAMMALIAN SENSORY CORTEX