Research Article: NMDA receptors are not necessary for burst firing of lateral habenula neurons in mice
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.
Introduction:
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.
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