My research is focused on understanding the mechanisms by which experience controls the development of the brain. My lab addresses this fundamental question by examining the development of the visual system in albino Xenopus tadpoles and the development of the spinal cord in Zebrafish. The visual system of Xenopus is well known for its experience-dependent plasticity. We have established this preparation as an excellent experimental system in which to conduct in vivo time lapse imaging studies of neuronal development and synaptogenesis, combined with both gene transfer and electrophysiological studies of visual system function. Over the past 15 years we have demonstrated a role for afferent coactivity, postsynaptic NMDA receptor activity, and downstream activation of calcium-dependent enzymes including CaMKII in controlling retinotectal synaptic maturation, optic tectal cell structural plasticity and topographic map formation (Wu et al., 1996; Zou and Cline, 1996; Wu and Cline, 1998; Zou and Cline, 1999; Ruthazer et al., 2003, 2006; Haas et al 2006). More recently, we have demonstrated that visual experience has multiple effects on visual system development. A relatively brief period, 4 hours, of visual experience enhances the growth rate of tectal cell dendritic arbors through a mechanism that requires glutamatergic transmission and the RhoA GTPases (Li et al., 2000; Li et al., 2002; Sin et al., 2002). This same brief period of visual experience increases the excitability of tectal neurons and their sensitivity to visual stimuli, through a mechanism that requires intracellular polyamines, the modulation of AMPA receptor function and compensatory changes in sodium channel activity (Aizenman et al., 2002, 2003).

          The finding that we can use visual stimulation to modify the development and properties of the retinotectal system has spurred our interest in determining the function of activity-induced genes on visual system plasticity. For instance, our studies of Homer, Arc and CPG15 demonstrate that each has distinct roles in controlling neuronal plasticity. Homer is a widely expressed scaffold protein, which affects calcium signaling and metabotropic glutamate receptor (mGluR) signaling. In addition to finding a role in axon guidance (Foa et al., 2001; Foa et al., 2005), our more recent work indicates that experience-dependent changes in postsynaptic Homer expression regulates mGluR-mediated plasticity of retinotectal transmission (Jensen, 2006). This is particularly interesting in light of recent work suggesting that mGluR-mediated potentiation and depression of synaptic transmission may play a role in developmental neurological disorders such as Fragile X. CPG15, another activity-induced protein, is noteworthy because it a GPI-linked signaling molecule whose expression results in a large increase in dendritic arbor development, coupled with an increase in glutamatergic retinotectal synaptic maturation and a coordinated elaboration of presynaptic retinal axon arbors (Nedivi et al., 1998; Cantallops et al., 2000; Nedivi et al., 2001). We have recently shown that CPG15 mediates these changes by promoting synapse formation, which in turn enhances axonal arbor growth (Javaherian and Cline, 2005). These data suggest that CPG15 is akin to an activity-induced targeted growth factor. It now appears that many activity induced genes function in a homeostatic manner to maintain synaptic strength within a functional operating range, despite experience-dependent increases or decreases in synaptic strength. This is the case for Arc (Rial Verde et al., 2006) and Homer, as well as ornithine decarboxylase, which generates polyamines and thereby regulates neuronal excitability and the strength of glutamatergic synaptic transmission.