Abstract

Slice preparations are typically used to study the effects of pharmacological manipulations on the electrophysiological activity of mature neurons. However, the severing of afferent inputs is known to significantly change the natural membrane activity of the neuron. To study the effects of local pharmacological manipulations on neurons in the intact brain, we combined the methods of microdialysis and intracellular recording in vivo. After implantation of a microdialysis probe into the prefrontal cortex (PFC) or striatum, intracellular recordings were conducted within ∼500 μm of the active surface of the probe. The spontaneous membrane activity, passive membrane properties, and intracellularly and synaptically evoked responses of striatal and cortical neurons recorded during perfusion of artificial cerebral spinal fluid were not different from that of neurons recorded in intact animals. Moreover, in the PFC, local perfusion with glutamate orN-methyl-d-aspartate depolarized neurons and increased spike activity. Conversely, local perfusion of tetrodotoxin hyperpolarized neurons while markedly reducing spontaneous membrane depolarizations and eliminating spike activity. In the striatum, local perfusion of the γ-aminobutyric acid_A receptor antagonist bicuculline rapidly depolarized neurons and increased spontaneous spike activity. Given that striatal and PFC neurons recorded in animals undergoing microdialysis in the current study exhibited electrophysiological properties similar to those recorded in intact controls, it is likely that the effects of local microdialysis on ongoing synaptic activity, neuronal excitability, and endogenous neurotransmitter levels are minimal. We conclude that the use of local microdialysis with intracellular recording is a powerful method for studying local receptor regulation of synaptic activity in vivo.