In vitro and in vivo physiology of low nanomolar concentrations of Zn(2+) in artificial cerebrospinal fluid

Artificial cerebrospinal fluid (ACSF), i.e., brain extracellular medium, which includes Ca(2+) and Mg(2+), but not other divalent cations such as Zn(2+), has been used for in vitro and in vivo experiments. The present study deals with the physiological significance of extracellular Zn(2+) in ACSF. Spontaneous presynaptic activity is suppressed in the stratum lucidum of brain slices from young rats bathed in ACSF containing 10 nM ZnCl(2), indicating that extracellular Zn(2+) modifies hippocampal presynaptic activity. To examine the in vivo action of 10 nM ZnCl(2) on long-term potentiation (LTP), the recording region was perfused using a recording electrode attached to a microdialysis probe. The magnitude of LTP was not modified in young rats by perfusion with ACSF containing 10 nM ZnCl(2), compared to perfusion with ACSF without Zn(2+), but attenuated by perfusion with ACSF containing 100 nM ZnCl(2). Interestingly, the magnitude of LTP was not modified in aged rats even by perfusion with ACSF containing 100 nM ZnCl(2), but enhanced by perfusion with ACSF containing 10 mM CaEDTA, an extracellular Zn(2+) chelator. The present study indicates that the basal levels of extracellular Zn(2+), which are in the range of low nanomolar concentrations, are critical for synaptic activity and perhaps increased age-dependently.