Prof. Martha Constantine-Paton

The development of the vertebrate brain involves a phase of synaptogenesis during which the activity patterns of young neurons mediate a competition that allows only highly effective synapses to survive. These activity-dependent developmental events are responsible for many of the adaptive changes in brain wiring as children mature and it is also likely to be responsible for some of the devastating and permanent behavioral effects of genetically or environmentally caused disruptions in normal early brain activity. We are investigating the mechanisms involved in this developmental synaptic plasticity. Specifically we are trying to dissect the signaling cascades through which synaptic activity determines which young synapses will be withdrawn and which ones will be retained to mediate adult brain function. Our approach is to work both in vivo and in vitro allowing normal developmental changes in brain structure or function to identify key molecular players that can subsequently be systematically studied in brain slices, dissociated primary neuron cultures and in intact animals with important synaptic molecules either "knocked out" or knocked down with with short inhibitory RNAs. Most of our work concentrates on the glutamatergic and GABAergic neurotransmitter systems in the midbrain optic lobes, (the superior colliculus) and the visual cortex of rodents. Recently we have been focusing on the events that rapidly follow an important event in visual pathway development: namely eye opening. We have shown that the ability to produce long duration increases in synaptic strength develops rapidly in the visual regions of the superior collciulus. Moreover, in layer IV of the visual cortex, these neurons that receive visual axons from the thalamus behave as if their synapses suddenly become fully potentiated: their post-synaptic evoked currents are generally larger than before eye opening and, in response to low frequency long trains of stimulation, the cells show high levels of synaptic depression. Along with these functional changes we have found that the cortical projection to the superior colliculus refines within 2 days of eye opening and the onset of pattern vision. This brings the 2 maps of visual space in the cortex and in the superior colliculus into register allowing the colliculus to initiate visually quided behavior. By contrast maintaining the eyes closed for 3-4 days beyond normal eye opening causes the corticocollicular axons to lose all branches! However, if eyes are opened on the 4th day after normal eye opening and the pups are examined several days later than the cortical neuron axon terminals in the colliculus start sprouting again. Obviously there is a continued activity-dependent structural (and also a functional plasticity) that is maintained for at least a week after eye opening and we are in the process of dissecting the mechanisms underlying this plasticity.