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Astrocytes promote the formation and function of excitatory synapses in the CNS. However, whether and how astrocytes modulate inhibitory synaptogenesis are essentially unknown. We asked whether astrocytes regulate the formation of inhibitory synapses between hippocampal neurons during maturation in vitro. Neuronal coculture with astrocytes or treatment with astrocyte-conditioned medium (ACM) increased the number of inhibitory presynaptic terminals, the frequency of miniature IPSCs, and the number and synaptic localization of GABA A receptor (GABA A R) clusters during the first 10 d in vitro. We asked whether neurotrophins, which are potent modulators of inhibitory synaptic structure and function, mediate the effects of astrocytes on inhibitory synapses. ACM from BDNF-or tyrosine receptor kinase B (TrkB)-deficient astrocytes increased inhibitory presynaptic terminals and postsynaptic GABA A R clusters in wild-type neurons, suggesting that BDNF and TrkB expression in astrocytes is not required for these effects. In contrast, although the increase in the number of inhibitory presynaptic terminals persisted, no increase was observed in postsynaptic GABA A R clusters after ACM treatment of hippocampal neurons lacking BDNF or TrkB. These results suggest that neurons, not astrocytes, are the relevant source of BDNF and are the site of TrkB activation required for postsynaptic GABA A R modulation. These data also suggest that astrocytes may modulate postsynaptic development indirectly by stimulating Trk signaling between neurons. Together, these data show that astrocytes modulate inhibitory synapse formation via distinct presynaptic and postsynaptic mechanisms.

The results of temperature-dependent dc conductivity, EPR magnetic susceptibility, and X-ray photoelectron spectroscopy (XPS) experiments are compared for electrochemically and chemically synthesized polypyrrole (PPy) samples. For chemically synthesized PPy samples soluble in organic solvent with large size dopants such as dodecylbenzenesulfonic acid (DBSA) or naphthalenesulfonic acid (NSA), dc conductivity (σ dc) is e0.1 S/cm at room temperature, and its temperature dependence [σdc(T)] shows strong localization behavior, while σdc(T) of the electrochemically synthesized PPy samples doped with hexafluorophosphate (PF6) is in the critical or the metallic regime. The density of states of chemically prepared PPy-DBSA samples is less than one-fourth that of electrochemically synthesized PPy-PF6 samples. The g values and temperature dependence of the line width obtained from EPR experiments show that the paramagnetic signals in both electrochemically and chemically synthesized PPy samples are mainly due to the polarons in π-conjugated polymer chains. We observe the existence of one dopant per three pyrrole rings in PPy-DBSA and PPy-PF6 samples. From the XPS experiments, one-fifth of the pyrrole rings of chemically prepared PPy-DBSA are incorporated into interchain links or side chains, while for electrochemically prepared PPy-PF6, one-third of the pyrrole units are in side chains or crosslinks. We analyze that the side chains or cross-links of chemically synthesized PPy samples are relatively reduced, and subsequently the interchain interaction weakens. For chemically synthesized PPy samples, the synthesis method using large size dopants is one of the important roles for the reduction of side chains or cross-links and for the increase of solubility. The weakness of the interchain interaction and the reduction of side chains or interchain links for PPy systems play an important role for charge transport.

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