Item

Abstract

Introduction. Lateral hypothalamus (LH) plays a crucial role in regulating the brain state, which is reflected in pupil dynamics that serve as a specific arousal indicator. The activation of awake promoting neurons in the LH leads to brain state changes that depend on stimulation frequencies. Animal behavior also varies depending on optogenetic stimulation frequencies of neurons in the LH. Although LH activation modulates both brain states and pupil dynamics, the influence of frequency-specific LH activation on brain state and pupil size regulations is under-examined. Since the LH also regulates the autonomic system, it is important to examine the relationship between LH-mediated brain state and pupil dynamic changes, which will help elucidate the dual regulatory roles played by the LH. Here, we activated CaMKII+ neurons in the LH of anesthetized rats and recorded pupil size changes and local field potentials (LFP) in the anterior cingulate cortex (ACC). Optogenetic activation of the LH induced stimulation frequency-dependent pupil dilation and cortical LFP power changes. These results suggest that the LH can modulate both brain state and pupil dynamics with similar frequency-dependent regulatory mechanisms. Methods. We performed optogenetic stimulation on CaMKII+ neurons of the LH in five adult Sprague-Dawley rats under anesthesia and concurrently recorded LFP signals in the ACC and pupil size (Fig. 1a). All acquired data were processed with Matlab and DeepLabCut. Results. LH activation evoked robust LFP changes in the ACC (Fig. 1b) and pupil dilation (Fig. 1c). In particular, we observed LFP delta (1-4Hz) power reduction in the ACC with an exponential decay feature (Fig. 1d) and logarithmic growth of the maximum pupil diameter (Fig. 1e) as a function of optogenetic stimulation frequencies from 1 to 20Hz at the LH. Conclusion. This work shows that frequency-dependent optogenetic activation of the LH can induce pupil dilation and brain state modulation simultaneously in a similar manner, suggesting a distinctive up-regulatory role of the LH on both brain state and pupil dynamics.