In neurons, perisynaptic or dendritic translation is implicated in synapse-wide alterations of function and morphology triggered by neural activity. The molecular mechanisms controlling local translation activation, however, have yet to be elucidated. Here, we show that local protein synthesis and translational activation in neuronal dendrites are upregulated by brain-derived neurotrophic factor (BDNF) in a rapamycin and small interfering RNA specific for mammalian target of rapamycin (mTOR)-sensitive manner. In parallel, BDNF induced the phosphorylation of tuberin and the activation of mTOR in dendrites and the synaptoneurosome fraction. mTOR activation stimulated translation initiation processes involving both eIF4E/4E-binding protein (4EBP) and p70S6 kinase/ribosomal S6 protein. BDNF induced phosphorylation of 4EBP in isolated dendrites. Moreover, local puff application of BDNF to dendrites triggered S6 phosphorylation in a restricted area. Taken together, these data indicate that mTOR-dependent translation activation is essential for the upregulation of local protein synthesis in neuronal dendrites.

No abstract

Coordination of limb movements: three types of intersegmental interneurons in the swimmeret system and their responses to changes in excitation. During forward locomotion, the movements of swimmerets on different segments of the crayfish abdomen are coordinated so that more posterior swimmerets lead their anterior neighbors by approximately 25%. This coordination is accomplished by mechanisms within the abdominal nerve cord. Here we describe three different types of intersegmental swimmeret interneurons that are necessary and sufficient to accomplish this coordination. These interneurons could be identified both by their structures within their home ganglion and by their physiological properties. These interneurons occur as bilateral pairs in each ganglion that innervates swimmerets, and their axons traverse the minuscule tract (MnT) of their home ganglion before leaving to project to neighboring ganglia. Two types, ASCE and ASCL, projected an axon anteriorly; the third type, DSC, projected posteriorly. Each type fires a burst of impulses starting at a different phase of the swimmeret cycle in its home ganglion. In active preparations, excitation of individual ASCE or DSC interneurons at different phases in the cycle affected the timing of the next cycle in the interneuron's target ganglion. The axons of these interneurons that projected between two ganglia ran close together, and their firing often could be recorded by the same electrode. Experiments in which either this tract or the rest of the intersegmental connectives was cut bilaterally showed that these interneurons were both necessary and sufficient for coordination of neighboring swimmerets. When the level of excitation of the swimmeret system was increased by bath application of carbachol, the period of the system's cycle shortened, but the characteristic phase difference within and between ganglia was preserved. Each of these interneurons responded to this increase in excitation by increasing the frequency of impulses within each burst, but the phases and relative durations of their bursts did not change, and their activity remained coordinated with the cycle in their home ganglion. The decrease in duration of each burst was matched to the increase in impulse frequency within the burst so that the mean numbers of impulses per burst did not change significantly despite a threefold change in period. These three types of interneurons appear to form a concatenated intersegmental coordinating circuit that imposes a particular intersegmental phase on the local pattern generating modules innervating each swimmeret. This circuit is asymmetric, and forces posterior segments to lead each cycle of output.

No abstract

Neuregulin-1 (NRG1) signaling is thought to contribute to both neuronal development and schizophrenia neuropathology. Here, we describe the developmental effects of excessive peripheral NRG1 signals on synaptic activity and AMPA receptor expression of GABAergic interneurons in postnatal rodent neocortex. A core peptide common to all NRG1 variants (eNRG1) was subcutaneously administered to mouse pups. Injected eNRG1 penetrated the blood-brain barrier and activated ErbB4 NRG1 receptors in the neocortex, in which ErbB4 mRNA is predominantly expressed by parvalbumin-positive GABAergic interneurons. We prepared neocortical slices from juvenile mice that were receiving eNRG1 subchronically and recorded inhibitory synaptic activity from layer V pyramidal neurons. Postnatal eNRG1 treatment significantly enhanced polysynaptic IPSCs, although monosynaptic IPSCs were not affected. Examination of excitatory inputs to parvalbumin-containing GABAergic interneurons revealed that eNRG1 treatment significantly increased AMPA-triggered inward currents and the amplitudes and frequencies of miniature EPSCs (mEPSCs). Similar effects on mEPSCs were observed in mice treated with a soluble, full-length form of NRG1 type I. Consistent with the electrophysiologic data, expression of the AMPA receptor GluA1 (i.e., GluR1, GluRA) was upregulated in the postsynaptic density/cytoskeletal fraction prepared from eNRG1-treated mouse neocortices. Cortical GABAergic neurons cultured with eNRG1 exhibited a significant increase in surface GluA1 immunoreactivity at putative synaptic sites on their dendrites. These results indicate that NRG1 circulating in the periphery influences postnatal development of synaptic AMPA receptor expression in cortical GABAergic interneurons and may play a role in conditions characterized by GABA-associated neuropathologic processes.