Array tomography of physiologically-characterized CNS synapses.

BACKGROUND: The ability to correlate plastic changes in synaptic physiology with changes in synaptic anatomy has been very limited in the central nervous system because of shortcomings in existing methods for recording the activity of specific CNS synapses and then identifying and studying the same individual synapses on an anatomical level. NEW METHOD: We introduce here a novel approach that combines two existing methods: paired neuron electrophysiological recording and array tomography, allowing for the detailed molecular and anatomical study of synapses with known physiological properties. RESULTS: The complete mapping of a neuronal pair allows determining the exact number of synapses in the pair and their location. We have found that the majority of close appositions between the presynaptic axon and the postsynaptic dendrite in the pair contain synaptic specializations. The average release probability of the synapses between the two neurons in the pair is low, below 0.2, consistent with previous studies of these connections. Other questions, such as receptor distribution within synapses, can be addressed more efficiently by identifying only a subset of synapses using targeted partial reconstructions. In addition, time sensitive events can be captured with fast chemical fixation. COMPARISON WITH EXISTING METHODS: Compared to existing methods, the present approach is the only one that can provide detailed molecular and anatomical information of electrophysiologically-characterized individual synapses. CONCLUSIONS: This method will allow for addressing specific questions about the properties of identified CNS synapses, even when they are buried within a cloud of millions of other brain circuit elements.

Role of vanadium ions, oxygen vacancies, and interstitial zinc in room temperature ferromagnetism on ZnO-V2O5 nanoparticles.

In this work, we present the role of vanadium ions (V+5 and V+3), oxygen vacancies (VO), and interstitial zinc (Zni) to the contribution of specific magnetization for a mixture of ZnO-V2O5 nanoparticles (NPs). Samples were obtained by mechanical milling of dry powders and ethanol-assisted milling for 1 h with a fixed atomic ratio V/Zn?=?5% at. For comparison, pure ZnO samples were also prepared. All samples exhibit a room temperature magnetization ranging from 1.18?×?10-3 to 3.5?×?10-3 emu/gr. Pure ZnO powders (1.34?×?10-3 emu/gr) milled with ethanol exhibit slight increase in magnetization attributed to formation of Zni, while dry milled ZnO powders exhibit a decrease of magnetization due to a reduction of VO concentration. For the ZnO-V2O5 system, dry milled and thermally treated samples under reducing atmosphere exhibit a large paramagnetic component associated to the formation of V2O3 and secondary phases containing V+3 ions; at the same time, an increase of VO is observed with an abrupt fall of magnetization to σ?~?0.7?×?10-3 emu/gr due to segregation of V oxides and formation of secondary phases. As mechanical milling is an aggressive synthesis method, high disorder is induced at the surface of the ZnO NPs, including VO and Zni depending on the chemical environment. Thermal treatment restores partially structural order at the surface of the NPs, thus reducing the amount of Zni at the same time that V2O5 NPs segregate reducing the direct contact with the surface of ZnO NPs. Additional samples were milled for longer time up to 24 h to study the effect of milling on the magnetization; 1-h milled samples have the highest magnetizations. Structural characterization was carried out using X-ray diffraction and transmission electron microscopy. Identification of VO and Zni was carried out with Raman spectra, and energy-dispersive X-ray spectroscopy was used to verify that V did not diffuse into ZnO NPs as well to quantify O/Zn ratios.

The functional nature of synaptic circuitry is altered in area CA3 of the hippocampus in a mouse model of Down's syndrome.

Down's syndrome (DS) is the most common cause of mental retardation, and memory impairments are more severe in DS than in most if not all other causes of mental retardation. The Ts65Dn mouse, a genetic model of DS, exhibits phenotypes of DS, including memory impairments indicative of hippocampal dysfunction. We examined functional synaptic connectivity in area CA3 of the hippocampus of Ts65Dn mice using organotypic slice cultures as a model. We found reductions in multiple measures of synaptic function in both excitatory and inhibitory inputs to pyramidal neurons in CA3 of the Ts65Dn hippocampus. However, associational synaptic connections between pyramidal neurons were more abundant and more likely to be active rather than silent in the Ts65Dn hippocampus. Synaptic potentiation was normal in these associational connections. Decreased overall functional synaptic input onto pyramidal neurons expressed along with the specific hyperconnectivity of associational connections between pyramidal neurons will result in predictable alterations of CA3 network function, which may contribute to the memory impairments seen in DS.