UC San Diego

Within a neuron, calcium can depolarize the membrane to initiate or propagate an action potential and can serve as a second messenger to influence gene transcription or cytoskeletal arrangement. In these capacities, calcium plays diverse roles during neuronal development. Here I describe novel roles that calcium plays in neurotransmitter specification, neurite outgrowth, and sensory innervation. Neurotransmitters are essential for interneuronal signaling, and the specification of appropriate transmitters in differentiating neurons has been related to intrinsic neuronal identity and to extrinsic signaling proteins. Altering the distinct patterns of Ca²⁺ spike activity spontaneously generated by different classes of embryonic spinal neurons in vivo changes the transmitter that neurons express without affecting the expression of markers of cell identity. Regulation seems to be homeostatic: suppression of activity leads to an increased number of neurons expressing excitatory transmitters and a decreased number of neurons expressing inhibitory transmitters; the reverse occurs when activity is enhanced. The imposition of specific spike frequencies in vitro does not affect labels of cell identity but again specifies the expression of transmitters that are inappropriate for the markers they express, during an early critical period. These results identify a new role of patterned activity in development of the central nervous system. Axons and dendrites of developing neurons establish distributed innervation patterns enabling precise discrimination in sensory systems. I describe the role of the extracellular matrix molecule, laminin [beta]-2, interacting with the CaV2.2 calcium channel in establishing appropriate sensory innervation. In vivo, CaV2.2 is expressed on the growth cones of Xenopus laevis sensory neurites and laminin [beta]-2 is expressed in the skin. Culturing neurons on a laminin beta-2 substrate inhibits neurite outgrowth in a specific and calcium-dependent manner. Blocking signaling between laminin beta-2 and CaV2.2 leads to increased numbers of sensory terminals in vivo. These findings suggest that interactions between extracellular matrix molecules and calcium channels regulate connectivity in the developing nervous system