Gaboxadol Normalizes Behavioral Abnormalities in a Mouse Model of Fragile X Syndrome.

Fragile X syndrome (FXS) is the most common inherited form of intellectual disability and autism. FXS is also accompanied by attention problems, hyperactivity, anxiety, aggression, poor sleep, repetitive behaviors, and self-injury. Recent work supports the role of γ-aminobutyric-acid (GABA), the primary inhibitory neurotransmitter in the brain, in mediating symptoms of FXS.

Semaphorin 3A induces CaV2.3 channel-dependent conversion of axons to dendrites.

Polarized neurites (axons and dendrites) form the functional circuitry of the nervous system. Secreted guidance cues often control the polarity of neuron migration and neurite outgrowth by regulating ion channels. Here, we show that secreted semaphorin 3A (Sema3A) induces the neurite identity of Xenopus spinal commissural interneurons (xSCINs) by activating Ca(V)2.

Cyclic GMP-gated CNG channels function in Sema3A-induced growth cone repulsion.

Cyclic nucleotide-gated channels (CNGCs) transduce external signals required for sensory processes, e.g., photoreception, olfaction, and taste.

Membrane potential shifts caused by diffusible guidance signals direct growth-cone turning.

Plasma membrane potentials gate the ion channel conductance that controls external signal-induced neuronal functions. We found that diffusible guidance molecules caused membrane potential shifts that resulted in repulsion or attraction of Xenopus laevis spinal neuron growth cones. The repellents Sema3A and Slit2 caused hyperpolarization, and the attractants netrin-1 and BDNF caused depolarization.