Neural correlates of multidimensional motor outputs in an excitatory parafascicular-zona incerta circuit.

The parafascicular nucleus (Pf) in medial thalamus is interconnected with prefrontal cortex and basal ganglia. Though much research has determined its importance in cognitive regulation of behaviour, its projections to regions in subthalamus remain less known. Such connections include those to zona incerta (ZI), located immediately dorsal to subthalamic nuclei (STN) regulating motor output, and whose role in a motor context is only beginning to be investigated. We thus examined circuits from parafascicular (Pf) thalamus to ZI, and its activity during locomotion and spontaneous behaviours in mice. We found that a distinct group of CaMKIIα-positive excitatory parafascicular neurons, separated from VGLUT2-positive excitatory neurons, project widely into ZI, more than adjacent STN. Our results from fibre photometry and decoding with general linear model (GLM) indicate that PF-ZI pathways do not specifically correlate with amount of locomotion or movement velocity, but instead show more specified activity during relative directional changes of movements observed in turning, sniffing behaviours. These results hint at the PF-ZI pathway having a distinct role in directing action specificity and have implications for subcortical bases in dimensional control of behaviours.

Protocol for in vivo dual-color fiber photometry in the mouse thalamus.

In vivo calcium imaging of neural activity is an indispensable approach for understanding the mechanisms and functions of neural system. Development of advanced imaging tools and various genetically encoded calcium indicators allows us to simultaneously record the activity of different neural populations. Here, we present a protocol for acquiring neural activity of two discrete neural populations in mice using dual-color fiber photometry. We describe steps for injecting viral constructs and implanting the fiber optic through stereotaxic surgery, calcium signal acquisition, and data analysis. We also describe the incorporation of electroencephalogram and electromyography recordings with dual-color fiber photometry analysis. For complete details on the use and execution of this protocol, please refer to Shin et al.1.

A brainstem-to-mediodorsal thalamic pathway mediates sound-induced arousal from slow-wave sleep.

Auditory-induced arousal is a defense mechanism of animals against potential dangers. Although the thalamus is the neural substrate that relays sensory information to the cortex, its function is reduced during slow-wave sleep (SWS), also known as deep sleep. Despite this, animals are capable of waking up in response to external sensory stimuli, suggesting the existence of neural circuits that are involved in this response. Here, we report that kainate-class-type ionotropic glutamate receptor subunit 4 (GRIK4)-positive mediodorsal (MD) thalamic neurons act as a neural substrate for arousals from SWS. These neurons become active during arousal from SWS and their photoactivation can induce arousal from SWS. Moreover, we show that these neurons are influenced by glutamatergic neurons in the brainstem, the activity of which increases during auditory-induced arousals. These results suggest that this brainstem-MD pathway can mediate wakefulness from SWS.