Orchestrating appropriate behavioral responses in the face of competing signals that predict either rewards or threats in the environment is crucial for survival. The basolateral amygdala (BLA) and prelimbic (PL) medial prefrontal cortex (mPFC) have been implicated in reward-seeking and fear-related responses, but how information flows between these reciprocally-connected structures to coordinate behavior is unknown. We recorded neuronal activity from the BLA and PL while rats performed a task where in shock- and sucrose-predictive cues were simultaneously presented to induce competition. The correlated firing primarily displayed a BLA→PL directionality during the shock-associated cue. Furthermore, the majority of optogenetically-identified PL-projecting BLA neurons recorded encoded the shock-associated cue, and more accurately predicted behavioral responses during competition than unidentified BLA neurons. Finally, BLA→PL photostimulation increased freezing, whereas both chemogenetic and optogenetic inhibition reduced freezing. The BLA→PL circuit plays a critical role in governing the selection of behavioral responses in the face of competing signals.
Despite abundant evidence that dopamine (DA) modulates medial prefrontal cortex (mPFC) activity to mediate diverse behavioral functions 1,2 , the precise circuit computations remain elusive. One potentially unifying model by which DA can underlie a diversity of functions is to modulate the signal-to-noise ratio (SNR) in subpopulations of mPFC neurons [3][4][5][6] , where neural activity conveying sensory information (signal) is amplified relative to spontaneous firing (noise). Here, we demonstrate that DA increases the SNR of responses to aversive stimuli in mPFC neurons projecting to the dorsal periaqueductal gray (dPAG). Using electrochemical approaches, we reveal the precise time course of pinch-evoked DA release in the mPFC, and show that mPFC DA biases behavioral responses to aversive stimuli. Activation of mPFC-dPAG neurons is sufficient to drive place avoidance and defensive behaviors. mPFC-dPAG neurons displayed robust shock-induced excitations, as visualized by single-cell, projection-defined microendoscopic calcium imaging. Finally, photostimulation of DA terminals in the mPFC revealed an increase in SNR in mPFC-dPAG responses to aversive stimuli. Together, these data highlight how mPFC DA can route sensory information in a valence-specific manner to different downstream circuits.Users may view, print, copy, and download text and data-mine the content in such documents, for the purposes of academic research, subject always to the full Conditions of use:http://www.nature.com/authors/editorial_policies/license.html#termsReprints and permissions information is available at www.nature.com/reprints.
What individual differences in neural activity predict the future escalation of alcohol drinking from casual to compulsive? The neurobiological mechanisms that gate the transition from moderate to compulsive drinking remain poorly understood. We longitudinally tracked the development of compulsive drinking across a binge-drinking experience in male mice. Binge drinking unmasked individual differences, revealing latent traits in alcohol consumption and compulsive drinking despite equal prior exposure to alcohol. Distinct neural activity signatures of cortical neurons projecting to the brainstem before binge drinking predicted the ultimate emergence of compulsivity. Mimicry of activity patterns that predicted drinking phenotypes was sufficient to bidirectionally modulate drinking. Our results provide a mechanistic explanation for individual variance in vulnerability to compulsive alcohol drinking.
The postoperative delirium in older adults guideline project was initiated by selecting an interdisciplinary, multi-specialty 23 member panel. The panel was chosen by the American Geriatrics Society's Geriatrics-for-Specialists Initiative (AGS-GSI) council with additional input from the panel co-chairs, with the goal of selecting participants with special interest and expertise in postoperative delirium. Represented disciplines included the fields of geriatric medicine, general surgery, anesthesiology, emergency medicine, geriatric surgery, gynecology, hospital medicine, critical care medicine, neurology, neurosurgery, nursing, obstetrics and gynecology, orthopedic surgery, ophthalmology, otolaryngology, palliative care, pharmacy, psychiatry, physical medicine and rehabilitation, thoracic surgery, urology, and vascular surgery.Additional ex officio panel members included a representative from the National Committee for Quality Assurance (NCQA), a quality measures expert, and a caregiver representative. The following panel members served on the writing group for this best practices statement: Stacie Deiner, MD;Conflicts of interest were disclosed initially and updated three times during guideline development. Disclosures were reviewed by the entire panel and potential conflicts resolved by the co-chairs (see Appendix 1). LITERATURE REVIEWThe methods for postoperative delirium risk factors, screening (case finding), and diagnosis (Table 1, Topics I to III) were distinct from the other aims, because these topics were thoroughly addressed in recent high-quality guideline statements and systematic reviews upon which the recommendation statements in these sections were based. 4,20-22 Additionally, these topics were considered outside the scope of the main literature search, which focused on prevention and treatment of delirium in the perioperative setting. Key citations were included in the section summaries. Sections were drafted by panel groups and then refined with the committee co-chairs. Subsequently, full consensus of the panel was achieved for all recommendation statements and summary sections.The methods for the literature search for the aims addressing the pharmacologic and nonpharmacologic interventions for the prevention or treatment of postoperative delirium in older adults (Table 1, Topics IV to X) included comprehensive searches, targeted searches, and focused searches. A more detailed description of the search methods is found in the accompanying clinical guideline document. 19 Comprehensive searches (1988( to December 2013 in PubMed, Embase, and CINAHL used the search terms delirium, organic brain syndrome, and acute confusion and resulted in a total of 6,504 articles. Additional, alternative terms included for the prevention and treatment of delirium were the words prevention, management, treatment, intervention, therapy, therapeutic, and drug therapy. Two additional targeted searches using the U.S. Library of National Medicine PubMed Special Queries on Comparative EffectivenessResearch and PubMed Cli...
Editor’s Perspective What We Already Know about This Topic What This Article Tells Us That Is New Background Postoperative delirium and postoperative cognitive dysfunction share risk factors and may co-occur, but their relationship is not well established. The primary goals of this study were to describe the prevalence of postoperative cognitive dysfunction and to investigate its association with in-hospital delirium. The authors hypothesized that delirium would be a significant risk factor for postoperative cognitive dysfunction during follow-up. Methods This study used data from an observational study of cognitive outcomes after major noncardiac surgery, the Successful Aging after Elective Surgery study. Postoperative delirium was evaluated each hospital day with confusion assessment method–based interviews supplemented by chart reviews. Postoperative cognitive dysfunction was determined using methods adapted from the International Study of Postoperative Cognitive Dysfunction. Associations between delirium and postoperative cognitive dysfunction were examined at 1, 2, and 6 months. Results One hundred thirty-four of 560 participants (24%) developed delirium during hospitalization. Slightly fewer than half (47%, 256 of 548) met the International Study of Postoperative Cognitive Dysfunction-defined threshold for postoperative cognitive dysfunction at 1 month, but this proportion decreased at 2 months (23%, 123 of 536) and 6 months (16%, 85 of 528). At each follow-up, the level of agreement between delirium and postoperative cognitive dysfunction was poor (kappa less than .08) and correlations were small (r less than .16). The relative risk of postoperative cognitive dysfunction was significantly elevated for patients with a history of postoperative delirium at 1 month (relative risk = 1.34; 95% CI, 1.07–1.67), but not 2 months (relative risk = 1.08; 95% CI, 0.72–1.64), or 6 months (relative risk = 1.21; 95% CI, 0.71–2.09). Conclusions Delirium significantly increased the risk of postoperative cognitive dysfunction in the first postoperative month; this relationship did not hold in longer-term follow-up. At each evaluation, postoperative cognitive dysfunction was more common among patients without delirium. Postoperative delirium and postoperative cognitive dysfunction may be distinct manifestations of perioperative neurocognitive deficits.
The abstracted set of recommendations presented here provides essential guidance both on the prevention of postoperative delirium in older patients at risk of delirium and on the treatment of older surgical patients with delirium, and is based on the 2014 American Geriatrics Society (AGS) Guideline. The full version of the guideline, American Geriatrics Society Clinical Practice Guideline for Postoperative Delirium in Older Adults is available at the website of the AGS. The overall aims of the study were twofold: first, to present nonpharmacologic and pharmacologic interventions that should be implemented perioperatively for the prevention of postoperative delirium in older adults; and second, to present nonpharmacologic and pharmacologic interventions that should be implemented perioperatively for the treatment of postoperative delirium in older adults. Prevention recommendations focused on primary prevention (i.e., preventing delirium before it occurs) in patients who are at risk for postoperative delirium (e.g., those identified as moderate-to-high risk based on previous risk stratification models such as the National Institute for Health and Care Excellence (NICE) guidelines, Delirium: Diagnosis, Prevention and Management. Clinical Guideline 103; London (UK): 2010 July 29). For management of delirium, the goals of this guideline are to decrease delirium severity and duration, ensure patient safety and improve outcomes.
We examined the ability of neuronal ensembles from rat motor cortex to predict behavioral performance during a reaction time task. We found that neurons that were the best individual predictors of task performance were not necessarily the neurons that contributed the most predictive information to an ensemble of neurons. To understand this result, we applied a framework for quantifying statistical relationships between neurons (Schneidman et al., 2003) to all possible combinations of neurons within our ensembles. We found that almost all neurons (96%) contributed redundant predictive information to the ensembles. This redundancy resulted in the maintenance of predictive information despite the removal of many neurons from each ensemble. Moreover, the balance of synergistic and redundant interactions depended on the number of neurons in the ensemble. Small ensembles could exhibit synergistic interactions (e.g., 23 Ϯ 9% of ensembles with two neurons were synergistic). In contrast, larger ensembles exhibited mostly redundant interactions (e.g., 99 Ϯ 0.1% of ensembles with eight neurons were redundant). We discuss these results with regard to constraints on interpreting neuronal ensemble data and with respect to motor cortex involvement in reaction time performance.
Successful foragers respond flexibly to environmental stimuli. Behavioral flexibility depends on a number of brain areas that send convergent projections to the medial striatum, such as the medial prefrontal cortex, orbital frontal cortex, and amygdala. Here, we tested the hypothesis that neurons in the medial striatum are involved in flexible action selection, by representing changes in stimulus-reward contingencies. Using a novel Go/No-go reaction-time task, we changed the reward value of individual stimuli within single experimental sessions. We simultaneously recorded neuronal activity in the medial and ventral parts of the striatum of rats. The rats modified their actions in the task after the changes in stimulus-reward contingencies. This was preceded by dynamic modulations of spike activity in the medial, but not the ventral, striatum. Our results suggest that the medial striatum biases animals to collect rewards to potentially valuable stimuli and can rapidly influence flexible behavior.
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