RhoGTPase Regulators Orchestrate Distinct Stages of Synaptic Development

Small RhoGTPases regulate changes in post-synaptic spine morphology and density that support learning and memory. They are also major targets of synaptic disorders, including Autism. Here we sought to determine whether upstream RhoGTPase regulators, including GEFs, GAPs, and GDIs, sculpt specific stages of synaptic development. The majority of examined molecules uniquely regulate either early spine precursor formation or later matura- tion. Specifically, an activator of actin polymerization, the Rac1 GEF β-PIX, drives spine pre- cursor formation, whereas both FRABIN, a Cdc42 GEF, and OLIGOPHRENIN-1, a RhoA GAP, regulate spine precursor elongation. However, in later development, a novel Rac1 GAP, ARHGAP23, and RhoGDIs inactivate actomyosin dynamics to stabilize mature synap- ses. Our observations demonstrate that specific combinations of RhoGTPase regulatory pro- teins temporally balance RhoGTPase activity during post-synaptic spine development

A-, T-, and H-type Currents Shape Intrinsic Firing of Developing Rat Abducens Motoneurons

During postnatal development, profound changes take place in the excitability of nerve cells, including modification in the distribution and properties of receptor-operated channels and changes in the density and nature of voltage-gated channels. We studied here the firing properties of abducens motoneurons (aMns) in transverse brainstem slices from postnatal day (P) 1–13 rats. Recordings were made from aMNs in the whole-cell configuration of the patch-clamp technique. Two main types of aMn could be distinguished according to their firing profile during prolonged depolarizations. Both types were identified as aMns by their fluorescence following retrograde labelling with the lipophilic carbocyanine DiI in the rectus lateralis muscle. The first type (BaMns) exhibited a burst of action potentials (APs) followed by an adaptation of discharge and were encountered in ∼70 % of aMns. Their discharge profile resembled that of adult aMns and was encountered in all aMns after P9. BaMns exhibited a hyperpolarization-induced rebound potential that was blocked by low concentrations of Ni2+ or by Ca2+-free external solution. This current had the properties of the T-type current. Action potentials of BaMns showed a complex afterhyperpolarization (AHP). An inward rectification was evidenced following hyperpolarization and was blocked by external application of caesium or ZD7288, indicating the presence of the hyperpolarization-activated cationic current (IH). Blocking the IH current almost doubled the input resistance of BaMns. The second class of aMns (DaMns) displayed a delayed excitation that was mediated by A-type K+ currents and was observed only between P4 and P9. DaMns exhibited immature characteristics: an action potential with a simple AHP, a linear current-voltage relation and a large input resistance. The number of aMns remained unchanged when both types were present (P5–P6) and later in development when only BaMns were encountered (P19), suggesting that DaMns mature into BaMns during postnatal development. We conclude that aMns display profound reorganization in their intrinsic excitability during postnatal development