Direct examination of lacal regualtion of membrane activityin striatal and prefrontal cortical neurons in vivousing simultaneous intracellular recording and microdialysis

摘要

Slice preparations are typically used tostudy the efects of pharmacological manipulations on the electrophysiological activity of mature neurons.However,the severing of afferent inputs is known to singnificantly change the natural membrane activity of the neuron.Tostudy the effects of local pharmacological manipulatios on neurons in theintact brain,we combined the methods of microdialysis and intracellular recording in vivo.After implantatin of a microdialysis probe into the prefrontal cortex(PFC) or striatum,intracellular recordings were conducted within approx500 #mu#m of the active surface of the active surface of the probe.The spontaneous memrane activity,passive membrane properties,and intracellularly and synaptically evoked responses of striatal and corticalneurons recorded during perfusionof artificial cerebralspinal fluid were not different from that of neurons recorded in intact animals.Moreover,in the PFC,local perfusion with glutamate or N-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 #gamma#-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 electrophy siological properties similar to those recorded in intact controls,it is likely that the effects of local icrodialysis on on going 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.