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

Background 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. Methods 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. Results 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. Conclusions NMDARs are not necessary for the generation of burst firing in LHb neurons, although they may play a modulating role under certain states.