Summary Abnormal nuclear size and shape are hallmarks of aging and cancer [1, 2]. However, the mechanisms regulating nuclear morphology and nuclear envelope (NE) expansion are poorly understood. In metazoans, the NE disassembles prior to chromosome segregation and reassembles at the end of mitosis [3]. In budding yeast, the NE remains intact. The nucleus elongates as chromosomes segregate and then divides at the end of mitosis to form two daughter nuclei without NE disassembly. The budding yeast nucleus also undergoes remodeling during a mitotic arrest; the NE continues to expand despite the pause in chromosome segregation, forming a nuclear extension, or “flare”, that encompasses the nucleolus [4]. The distinct nucleolar localization of the mitotic flare indicates that the NE is compartmentalized and that there is a mechanism by which NE expansion is confined to the region adjacent to the nucleolus. Here we show that mitotic flare formation is dependent on the yeast polo kinase, Cdc5. This function of Cdc5 is independent of its known mitotic roles, including rDNA condensation. High-resolution imaging revealed that following Cdc5 inactivation, nuclei expand isometrically rather than forming a flare, indicating that Cdc5 is needed for NE compartmentalization. Even in an uninterrupted cell cycle, a small NE expansion occurs adjacent to the nucleolus prior to anaphase in a Cdc5-dependent manner. Our data provides the first evidence that polo kinase, a key regulator of mitosis [5], plays a role in regulating nuclear morphology and NE expansion.

Critical animal behaviors, especially among rodents, are guided by odors in remarkably well-coordinated manners, yet many extramodal sensory cues compete for cognitive resources in these ecological contexts. That rodents can engage in such odor-guided behaviors suggests that they can selectively attend to odors. Indeed, higher-order cognitive processes-such as learning, memory, decision making, and action selection-rely on the proper filtering of sensory cues based on their relative salience. We developed a behavioral paradigm to reveal that rats are capable of selectively attending to odors in the presence of competing extramodal stimuli. We found that this selective attention facilitates accurate odor-guided decisions, which become further strengthened with experience. Further, we uncovered that selective attention to odors adaptively sharpens their representation among neurons in the olfactory tubercle, an olfactory cortex region of the ventral striatum that is considered integral for evaluating sensory information in the context of motivated behaviors. Odor-directed selective attention exerts influences during moments of heightened odor anticipation and enhances odorant representation by increasing stimulus contrast in a signal-to-noise-type coding scheme. Together, these results reveal that rats engage selective attention to optimize olfactory outcomes. Further, our finding of attention-dependent coding in the olfactory tubercle challenges the notion that a thalamic relay is integral for the attentional control of sensory coding.

Rodent premotor cortex (M2) integrates information from sensory and cognitive networks for action selection and planning during goal-directed decision making. M2 function is regulated by cortical inputs and ascending neuromodulators, including norepinephrine (NE) released from the locus coeruleus (LC). LC-NE has been shown to modulate the signal to noise ratio of neural representations in target regions prior to decision execution, to increase the salience of relevant stimuli. Using rats performing a two-alternative forced choice task after administration of an adrenergic antagonist (propranolol), we show that action planning in M2 is mediated by adrenergic signaling. Loss of adrenergic signaling results in failure to suppress irrelevant action plans in M2 that disrupts decoding of cue related information, delays decision times, and increases trial omissions, particularly in females. Furthermore, we identify a potential mechanism for the sex bias in behavioral and neural changes after propranolol administration via differential expression of receptors across sexes, particularly on local inhibitory neurons. Overall, we show a critical role for adrenergic signaling in M2 during decision making by suppressing irrelevant information to enable efficient action planning and decision execution.

Critical animal behaviors, especially among rodents, are guided by odors in remarkably well-coordinated manners. While many extramodal sensory cues compete for cognitive resources in these ecological contexts, that rodents can engage in such odor-guided behaviors suggests that they selectively attend to odors. We developed an operant task to reveal that rats are indeed capable of selectively attending to odors in the presence of competing extramodal stimuli and found that this selective attention facilitates accurate odor-guided behavior. Further, we uncovered that attention to odors adaptively sharpens their representation among individual neurons in a brain region considered integral for odor-driven behaviors. Thus, selective attention contributes to olfaction in rodents in a manner analogous to that observed for other sensory systems in more cognitively-advanced animals. Main Text:From neonatal attachment and suckling responses (1-3), to selecting mates, finding food sources, and avoiding predators (4-6), rodent behavior is guided by olfactory stimuli in remarkably well-coordinated manners. The fact that these behaviors can be successfully orchestrated lends reason to believe that rodents must selectively attend to odors in these contexts at the expense of competing extramodal cues. For instance, during foraging for food and sniffing out food odors, a rat must simultaneously 'filter' out competing auditory and visual stimuli arising from irrelevant sources. While we know that rodents readily display shifting of attentional sets, including those involving odors (7), and even that they can display attention towards information from other modalities (8,9), whether selective attention regulates olfactory perception and odor coding remains unresolved. This question is of great importance given the prevalence of rodents as models for olfactory function and due to the fact that we know odordirected attention shapes olfaction in humans (10, 11).Given the aforementioned importance of olfaction for survival, we reasoned that olfactory brain centers would adaptively encode odor information in manners dependent upon attentional demands. Further, while there are many locations within the olfactory system which are modulated by attention in humans (10, 12) as a starting place to uncover cellular modulation by attention, we predicted that selective attention would shape the representation of odors within the ventral striatum (VS). This is reasonable given that the VS is a collection of brain regions important for evaluating sensory information in the context of motivated behaviors (13), a function considered integral for attention (14). Offering precedence for this is evidence provided by human functional imaging for increased hemodynamic responses to odors in the VS during attention (10,12), particularly in the olfactory tubercle region of the VS, which is extensively innervated by olfactory input (15,16). Notably, the olfactory system does not have a classic thalamic relay, a component widely considered to be integral to a...