Injecting the NMDAR antagonist MK-801 into mice produced a 10-fold higher density of c-Fos—a marker of neuronal activity—in the medial entorhinal cortex (MEC) compared to other forebrain regions. c-Fos was concentrated in layer 3 of the dorsal MEC. Parvalbumin (PV)-positive inhibitory neurons showed a spatial correlation with c-Fos: high and medium PV neurons correlated positively with c-Fos density, while low PV neurons correlated negatively. During postnatal development, PV expression appeared on day 12, two days before c-Fos emerged on day 16. The findings suggest that specific subtypes of inhibitory and excitatory neurons in local circuits are critical for sustained neuronal responses to NMDAR antagonists, and that dense PV input may be necessary for inducing c-Fos in MEC principal neurons.
Burst firing in the lateral habenula (LHb) is linked to depression, and ketamine blocks this firing to produce rapid antidepressant effects. This study investigated whether NMDA receptors (NMDARs) are necessary for burst firing in LHb neurons. Using brain slices from adult male mice, researchers recorded spontaneous and rebound burst firing while applying NMDAR antagonists D-AP5 and MK-801. Neither antagonist altered spontaneous or rebound burst firing: the percentage of neurons showing burst firing, burst frequency, and spikes per burst remained unchanged. The results indicate that NMDARs are not required for generating burst firing in LHb neurons, though they may modulate it under certain conditions.