Presynaptic pH and vesicle fusion in Drosophila larvae neurones.

Both intracellular pH (pHi) and synaptic cleft pH change during neuronal activity yet little is known about how these pH shifts might affect synaptic transmission by influencing vesicle fusion. To address this we imaged pH- and Ca(2+) -sensitive fluorescent indicators (HPTS, Oregon green) in boutons at neuromuscular junctions. Electrical stimulation of motor nerves evoked presynaptic Ca(2+) i rises and pHi falls (∼0.1 pH units) followed by recovery of both Ca(2+) i and pHi. The plasma-membrane calcium ATPase (PMCA) inhibitor, 5(6)-carboxyeosin diacetate, slowed both the calcium recovery and the acidification. To investigate a possible calcium-independent role for the pHi shifts in modulating vesicle fusion we recorded post-synaptic miniature end-plate potential (mEPP) and current (mEPC) frequency in Ca(2+) -free solution. Acidification by propionate superfusion, NH(4)(+) withdrawal, or the inhibition of acid extrusion on the Na(+)/H(+) exchanger (NHE) induced a rise in miniature frequency. Furthermore, the inhibition of acid extrusion enhanced the rise induced by propionate addition and NH(4)(+) removal. In the presence of NH(4)(+), 10 out of 23 cells showed, after a delay, one or more rises in miniature frequency. These findings suggest that Ca(2+) -dependent pHi shifts, caused by the PMCA and regulated by NHE, may stimulate vesicle release. Furthermore, in the presence of membrane permeant buffers, exocytosed acid or its equivalents may enhance release through positive feedback. This hitherto neglected pH signalling, and the potential feedback role of vesicular acid, could explain some important neuronal excitability changes associated with altered pH and its buffering.

Changing the terms of psychoanalysis. From object to space and the nature of the transition

This paper examines the two versions of DWW’s paper on transitional objects and transitional phenomena and compares the 1951 paper with other papers of the period to argue for the significant shift heralded by Winnicott and his approach. The paper goes on to discuss the extensive use of Winnicott’s ideas in a range of different disciplines and clinical conditions and argues for a careful rereading of Winnicott himself and his fundamental contribution.

Este artigo examina as duas versões do artigo de DWW sobre os objetos e fenômenos transicionais e compara a versão de 1951 com outros artigos do mesmo período, para discutir as mudanças feitas por Winnicott. O artigo pretende discutir o uso extensivo das idéias de Winnicott numa ampla escala de disciplinas diferentes e de circunstâncias clínicas, fazendo uma releitura cuidadosa destas duas versões e de sua contribuição fundamental.