In vitro and in vivo physiology of low nanomolar concentrations of Zn2+ 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.