SIMULTANEOUS SINGLE-CELL RECORDING AND MICRODIALYSIS WITHIN THE SAME BRAIN SITE IN FREELY BEHAVING RATS - A NOVEL NEUROBIOLOGICAL METHOD

We present a method for performing intracerebral microdialysis in free ly behaving rats while recording the firing of neurons within the dial ysis site. Studying hippocampal theta cells and complex-spike cells wi th this technique, it has been found that: (1) when the microdialysis fluid contained only artificial cerebrospinal fluid, both types of neu rons displayed normal electrical activity, (2) the simultaneous single -cell recording/microdialysis procedure could be readily performed for as long as 3 days, and (3) inclusion of drugs into the microdialysis fluid, at appropriate concentrations, caused clear changes in firing p attern. For example, microdialysis with 1% lidocaine completely abolis hed, whereas that with 50 mM K+ markedly increased, the neuronal elect rical activity. These cellular changes developed without apparent EEG or behavioral manifestations and were reversible. In some of the exper iments, the extracellular concentrations of glutamate and aspartate in the recording/dialysis site were also measured. The described method allows the extracellular environment of recorded brain cells to be man ipulated by drugs delivered through the microdialysis probe and simult aneously allows determination of the neurochemical composition of that environment over a remarkably long period of time and in intact, phys iologically functioning, neural networks. Such studies will provide ne w insights into the molecular basis of neuronal activity in the brain in the context of behavior, including learning.