The preoptic area (POA) is necessary for sleep, but the fundamental POA circuits have remained elusive. Previous studies showed that galanin (GAL)- and GABA-producing neurons in the ventrolateral preoptic nucleus (VLPO) express cFos after periods of increased sleep and innervate key wake-promoting regions. Although lesions in this region can produce insomnia, high frequency photostimulation of the POAGAL neurons was shown to paradoxically cause waking, not sleep. Here we report that photostimulation of VLPOGAL neurons in mice promotes sleep with low frequency stimulation (1–4 Hz), but causes conduction block and waking at frequencies above 8 Hz. Further, optogenetic inhibition reduces sleep. Chemogenetic activation of VLPOGAL neurons confirms the increase in sleep, and also reduces body temperature. In addition, chemogenetic activation of VLPOGAL neurons induces short-latency sleep in an animal model of insomnia. Collectively, these findings establish a causal role of VLPOGAL neurons in both sleep induction and heat loss.

The ability to learn that a stimulus no longer signals danger is known as extinction. A major characteristic of extinction is that it is context-dependent, which means that fear reduction only occurs in the same context as extinction training. In other contexts, there is re-emergence of fear, known as contextual renewal. The ability to properly extinguish fear memories and generalize safety associations to multiple contexts provides therapeutic potential, but little is known about the specific neural pathways that mediate fear renewal and extinction generalization. The ventral hippocampus (VH) is thought to provide a contextual gating mechanism that determines whether fear or safety is expressed in particular contexts through its projections to areas of the fear circuit, including the infralimbic (IL) and prelimbic (PL) cortices. Moreover, VH principal cells fire in large, overlapping regions of the environment, a characteristic that is ideal to support generalization; yet it is unclear how different projection cells mediate this process. Using a pathway-specific (intersectional) chemogenetic approach, we demonstrate that selective activation of VH cells projecting to PL attenuates fear renewal without affecting fear expression. These results have implications for anxiety disorders since they uncover a neural pathway associated with extinction generalization.

BackgroundPrior studies of oculomotor function in Parkinson’s disease (PD) have either focused on saccades without considering smooth pursuit, or tested smooth pursuit while excluding saccades. The present study investigated the control of saccadic eye movements during pursuit tasksand assessed the quality of binocular coordinationas potential sensitive markers of PD.MethodsObservers fixated on a central cross while a target moved toward it. Once the target reached the fixation cross, observers began to pursue the moving target. To further investigate binocular coordination, the moving target was presented on both eyes (binocular condition), or on one eye only (dichoptic condition).ResultsThe PD group made more saccades than age-matched normal control adults (NC) both during fixation and pursuit. The difference between left and right gaze positions increased over time during the pursuit period for PD but not for NC. The findings were not related to age, as NC and young-adult control group (YC) performed similarly on most of the eye movement measures, and were not correlated with classical measures of PD severity (e.g., Unified Parkinson’s Disease Rating Scale (UPDRS) score).DiscussionOur results suggest that PD may be associated with impairment not only in saccade inhibition, but also in binocular coordination during pursuit, and these aspects of dysfunction may be useful in PD diagnosis or tracking of disease course.

Highlights d Sleep deprivation improves memory in old mice but worsens it in young ones d Sleep deprivation decreases hippocampal flexibility and spindle counts in young mice d Increased spindle counts are associated with improved memory in old mice d Sleep deprivation improves the quality of hippocampal representations in old mice