Dr. Minmin Luo’s lab found that the nucleus incertus control locomotor speed, arousal, and hippocampal theta rhythms

On January 14, 2020, Dr. Minmin Luo’s laboratory published an article entitled “Control of Locomotor Speed, Arousal, and Hippocampal Theta Rhythms by the Nucleus Incertus” in Nature Communications. This work identified a key brain subcortical center that integratively controls locomotor speed, arousal, and memory-related hippocampal theta rhythms.

When navigating at fast speed through a complex environment, an animal requires high arousal to sustain an attentive state and actively uses spatial memory to update its awareness of environmental cues. Previous studies have provided many insights into the vertebrate neural circuits involved in locomotion, arousal, and memory. It remains unclear how these behavioral and physiological processes are coordinately organized.

Figure 1. The activity of NI NMB neurons is positive correlated with animal’s locomotor speed, arousal level, and hippocampal theta rhythms. We measured arousal level by monitoring pupil diameter, which is widely used in the field. Considering that hippocampal theta rhythms with a frequency range of 6-10 Hz, become more pronounced during spatial memory integration, we monitored theta rhythms to measure spatial memory.

Lu et al. found that Neuromedin B (NMB) neurons in the brainstem nucleus incertus (NI) control locomotor speed, arousal, and hippocampal theta rhythms by using a combination of fiber photometry of Ca²⁺ signals, optogenetic activation and inhibition, transsynaptic circuit mapping, electrophysiological recordings, and behavioral tests. They found that the activity of NI NMB neurons is significantly correlated with locomotor speed, arousal levels, and hippocampal theta power. Moreover, these processes were suppressed by optogenetic inhibition and were facilitated by optogenetic stimulation of NI NMB neuron activity. In a food chasing task, optogenetic inhibition of NI NMB neurons significantly disrupt animal’s locomotor speed and success rate of chasing food, suggesting that the NI is crucial for animal’s foraging and survival. Moreover, they demonstrated pharmacologically that the effect of NI activation on arousal and hippocampal theta are not secondary to locomotion nor arousal. Finally, they found that NI NMB neurons coordinately control locomotor speed, arousal, and hippocampal theta rhythms by sending out projections to a number of brain areas associated with these behavior and physiology.

These findings provide new insights into the neural circuit underlying coordinate control of locomotor speed, arousal, and spatial memory. Lihui Lu and Yuqi Ren from Minmin Luo’s lab are co-first authors of this paper. Other contributors include Tao Yu, Dr. Zhixiang Liu, Sice Wang, Dr. Lubin Tan, Dr. Jiawei Zeng, Qiru Feng, Dr. Rui Lin, Yang Liu from Minmin Luo’s lab, and Dr. Qingchun Guo from Chinese Institute for Brain Research, Beijing (CIBR), Beijing. Dr. Minmin Luo is the corresponding author. The work was supported by the Ministry of Science and Technology of China, National Natural Science Foundation of China, and Beijing Municipal Government, and was carried out at the National Institute of Biological Sciences, Beijing.

Original link: https://www.nature.com/articles/s41467-019-14116-y