NMDA receptors are not necessary for burst firing of lateral habenula neurons in mice.

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.

Study at a glance

Abstract

Burst firing in the lateral habenula (LHb) is enhanced under stress and depression, and ketamine blocks burst firing in LHb to exert a rapid antidepressant effect. Thus, burst firing in LHb may serve as a cellular mechanism of depression and a promising therapeutic target for developing novel antidepressants. However, the mechanisms underlying burst firing in LHb are not fully understood. The present study aims to investigate the contribution of N-methyl-D-aspartate receptor (NMDAR) to burst firing in LHb. C57BL/6J male mice aged 8 to 10 weeks were used in the present study. Whole-cell recording was performed in brain slices containing LHb. Spontaneous and rebound burst firings were recorded in current-clamp mode. The effect of NMDAR antagonists, D-2-Amino-5-phosphonovaleric acid (D-AP5) and dizocilpine (MK-801), on burst firing was assessed. Spontaneous burst firing in LHb neurons persisted in the presence of a specific NMDAR antagonist, D-AP5. The percentages of neurons with spontaneous burst firing, burst firing frequency, and spike number per burst were not different between in D-AP5-containing bath solution and in control bath solution. D-AP5 also did not affect ongoing spontaneous burst firing. Rebound burst firing was not affected in the presence of D-AP5, nor was ongoing rebound burst firing. Likewise, MK-801, a use-dependent, non-competitive NMDAR antagonist, did not affect rebound burst firing. NMDARs are not necessary for the generation of burst firing in LHb neurons, although they may play a modulating role under certain states.