Johns Hopkins School of Medicine

Mechanisms of Cortical Modification

Sensory experience has a profound influence in shaping the functional organization of the cerebral cortex. Over 30 years ago, Hubel and Wiesel described a critical period of postnatal development for the formation of binocular connections in cat visual cortex. They demonstrated that thisconnectivity can be dramatically altered by simple forms of sensory deprivation, such as the temporary closure of one eyelid (monoculardeprivation). Besides the obvious relevance of this neural plasticity to the development of visual capabilities in humans and animals, it seems likely hat similar processes form the basis for some forms of learning and memory in the adult brain. Indeed, visual cortical plasticity, like learning andmemory formation decreases with age and depend on the internal state of the animal. The research in this lab is directed toward elucidating thebasic mechanisms by which visual experience can modify cortical connections in the visual cortex, and how those mechanisms are regulated.

We investigate in visual cortical slices two forms of activity-dependent synaptic plasticity: long-term potentiation (LTP) and long-term depression (LTD). These two forms of synaptic plasticity are currently the most comprehensive models of the elementary mechanisms underlying naturallyoccurring plasticity. Research done the past few has established that LTP and LTD have the appropriate properties to account for important features of naturally-occurring synaptic modification in visual cortex. Furthermore, changes in LTP and LTD during development correlate withchanges in naturally-occurring synaptic modification.

We are currently focused on how synaptic inhibition and the action of neuromodulators regulate the induction of LTP and LTD duringdevelopment. The results of these investigation suggest two hypotheses. 1) The development of synaptic inhibition restricts the induction of LTPand LTD, and henceforth, the modification by experience to a short critical period. 2) The action of neuromodulators released during arousal is to enhance the induction LTP and LTD by orders of magnitude, thus enabling experience to modify the visual cortex. Our expectation is that by testing these specific hypothesis we are stand to gain a better understanding of how naturally occurring plasticity is regulated.