It has long been known that orofacial movements for feeding can be triggered, coordinated, and often rhythmically organized at the level of the brainstem, without input from higher centers. We uncover two nuclei that can organize the movements for ingesting fluids in mice. These neuronal groups, IRtPhox2b and Peri5Atoh1, are marked by expression of the pan-autonomic homeobox gene Phox2b and are located, respectively, in the intermediate reticular formation of the medulla and around the motor nucleus of the trigeminal nerve. They are premotor to all jaw-opening and tongue muscles. Stimulation of either, in awake animals, opens the jaw, while IRtPhox2b alone also protracts the tongue. Moreover, stationary stimulation of IRtPhox2b entrains a rhythmic alternation of tongue protraction and retraction, synchronized with jaw opening and closing, that mimics lapping. Finally, fiber photometric recordings show that IRtPhox2b is active during volitional lapping. Our study identifies one of the subcortical nuclei underpinning a stereotyped feeding behavior.

Registration of data to a common frame of reference is an essential step in the analysis and integration of diverse neuroscientific data modalities. To this end, volumetric brain atlases enable histological datasets to be spatially registered and analysed, yet accurate registration remains expertise-dependent and slow. We have trained a neural network, DeepSlice, to register mouse brain histology to the Allen Brain Atlas, retaining accuracy while improving speed by >1000 fold.

Background: The incentive sensitisation theory of addiction posits that drug-associated stimuli become imbued with incentive motivational properties, driving pathological drug seeking. However, pre-existing variability in the incentive salience to non-drug reward cues (‘sign trackers’ (STs); ‘goal trackers’ (GTs)) is also predictive of the desire for and relapse to cocaine and opioids. Here, we asked whether variation in propensity to attribute incentive salience to a food cue is predictive of reinstatement to the highly addictive psychostimulant methamphetamine (METH), and whether treatment with the promising anti-addiction therapy oxytocin differentially reduces METH behaviour between STs and GTs. Methods: Rats were trained to associate a Pavlovian cue with delivery of a sucrose pellet over 8 days. They then received jugular vein catheters for intravenous METH self-administration, followed by behavioural extinction, and cue-induced and METH-primed reinstatement to METH-seeking behaviours. Oxytocin was administered prior to self-administration and reinstatement tests. Results: Despite the self-administration of similar amounts of METH, STs reinstated more to METH cues than did GTs, yet METH-priming reinstated STs and GTs similarly. Furthermore, oxytocin attenuated cue-induced reinstatement more so in STs than in GTs, and reduced METH-primed reinstatement to a greater extent in the top quartile of reinstaters, indicating that oxytocin treatment may be most effective for those at highest risk of addiction. Conclusions: This pre-existing bias towards reward cues presents a possible tool to screen for METH addiction susceptibility and may be useful for understanding the neurobiology of addiction and for pharmacotherapeutic discovery.

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