No abstract

In photoemission spectra of strongly correlated systems one usually observes a satellite structure below the main peak. Description of such satellite structures in the commonly used GW approximation has been found to be insufficient. To account for these satellite structures that originate from shortrange correlations, we have developed a T -matrix formalism for performing ab initio calculations on real systems. The method is applied to Ni and we obtain a satellite structure below the Fermi level as well as a reduced exchange splitting. We also found a new interesting satellite structure above the Fermi level, which can be ascribed to particle-particle scattering. [S0031-9007(98)05337-X]

Key pointsr The synaptic organization of paravertebral sympathetic ganglia enables them to relay activity from the spinal cord to the periphery and thereby control autonomic functions, including blood pressure and body temperature.r The present experiments were done to reconcile conflicting observations in tissue culture, intact isolated ganglia and living animals. By recording intracellularly from dissociated neurons and intact ganglia, we found that when electrode damage makes cells leaky it could profoundly distort cellular excitability and the integration of synaptic potentials.r The experiments relied on the dynamic clamp method, which allows the creation of virtual ion channels by injecting current into a cell based upon a mathematical model and using rapid feedback between the model and cell.r The results support the hypothesis that sympathetic ganglia can produce a 2.4-fold amplification of presynaptic activity. This could aid understanding of the neural hyperactivity that is believed to drive high blood pressure in some patients. AbstractThe excitability of rat sympathetic neurons and integration of nicotinic EPSPs were compared in primary cell culture and in the acutely isolated intact superior cervical ganglion using whole cell patch electrode recordings. When repetitive firing was classified by Hodgkin's criteria in cultured cells, 18% displayed tonic class 1 excitability, 36% displayed adapting class 2 excitability and 46% displayed phasic class 3 excitability. In the intact ganglion, 71% of cells were class 1 and 29% were class 2. This diverges from microelectrode reports that nearly 100% of superior cervical ganglion neurons show phasic class 3 firing. The hypothesis that the disparity between patch and microelectrode data arises from a shunt conductance was tested using the dynamic clamp in cell culture. Non-depolarizing shunts of 3-10 nS converted cells from classes 1 and 2 to class 3 dynamics with current-voltage relations that replicated microelectrode data. Primary and secondary EPSPs recorded from the intact superior cervical ganglion were modelled as virtual synapses in cell culture using the dynamic clamp. Stimulating sympathetic neurons with virtual synaptic activity, designed to replicate in vivo recordings of EPSPs in muscle vasoconstrictor neurons, produced a 2.4-fold amplification of presynaptic activity. This gain in postsynaptic output did not differ between neurons displaying the three classes of excitability. Mimicry of microelectrode damage by virtual leak channels reduced and eventually obliterated synaptic gain by inhibiting summation of subthreshold EPSPs. These results provide a framework for interpreting sympathetic activity recorded from intact animals and support the hypothesis that paravertebral ganglia function as activity-dependent amplifiers of spinal output from preganglionic circuitry.

Plexiform neurofibroma, a benign peripheral nerve tumor, is associated with the biallelic loss of function of the NF1 tumor suppressor in Schwann cells. Here, we show that FLLL32, a small molecule inhibitor of JAK/STAT3 signaling, reduces neurofibroma growth in mice with conditional, biallelic deletion of Nf1 in the Schwann cell lineage. FLLL32 treatment or Stat3 deletion in tumor cells reduced inflammatory cytokine expression and tumor macrophage numbers in neurofibroma. Although STAT3 inhibition down-regulated the chemokines CCL2 and CCL12, which can signal through CCR2 to recruit macrophages to peripheral nerves, deletion of Ccr2 did not improve survival or reduce macrophage numbers in neurofibroma-bearing mice. Interestingly, macrophages accounted for ~20-40% of proliferating cells in untreated tumors. FLLL32 suppressed this proliferation, as well as Schwann cell proliferation, implicating STAT3-dependent, local proliferation in neurofibroma macrophage accumulation. The functions of STAT3 signaling in neurofibroma Schwann cells and macrophages, and its relevance as a therapeutic target in neurofibroma, merit further investigation.