Cortical Pyramidal Cells and Fast-spiking Interneurons

21 Tonically-activated neuronal currents mediated by N-methyl-D-aspartate receptors (NMDARs) 22 have been hypothesized to contribute to normal neuronal function as well as to neuronal 23 pathology resulting from excessive activation of glutamate receptors (e.g., excitotoxicity). While 24 cortical excitatory cells are very vulnerable to excitotoxic insult, the data regarding resistance of 25 inhibitory cells (or interneurons) are inconsistent. Types of neurons with more pronounced tonic 26 NMDAR current potentially associated with the activation of extrasynaptic NMDARs could be 27 expected to be more vulnerable to excessive activation by glutamate. In this study, we compare 28 tonic activation of NMDARs in excitatory pyramidal cells and inhibitory fast-spiking 29 interneurons in prefrontal cortical slices. We assessed tonic NMDAR current by measuring 30 holding current shift as well as noise reduction following NMDAR blockade after removal of 31 spontaneous glutamate release. In addition, we compared NMDAR miniature EPSCs in both cell 32 types. We demonstrate for the first time that tonic NMDAR currents are present in inhibitory 33 fast-spiking interneurons. We found that the magnitude of tonic NMDAR current is similar in 34 pyramidal cells and fast-spiking interneurons, and that quantal release of glutamate does not 35 significantly impact tonic NMDAR current. 36 37