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 freely behaving rats while recording the firing of neurons within the dialysis site. Studying hippocampal theta cells and complex-spike cells with this technique, it has been found that: (1) when the microdialysis fluid contained only artificial cerebrospinal fluid, both types of neurons 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 pattern. For example, microdialysis with 1% lidocaine completely abolished, whereas that with 50 mM K+ markedly increased, the neuronal electrical activity. These cellular changes developed without apparent EEG or behavioral manifestations and were reversible. In some of the experiments, 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 manipulated by drugs delivered through the microdialysis probe and simultaneously allows determination of the neurochemical composition of that environment over a remarkably long period of time and in intact, physiologically functioning, neural network. Such studies will provide new insights into the molecular basis of neuronal activity in the brain in the context of behavior, including learning.