A neural circuit for competing approach and defense underlying prey capture.

Predators must frequently balance competing approach and defensive behaviors elicited by a moving and potentially dangerous prey. Several brain circuits supporting predation have recently been localized. However, the mechanisms by which these circuits balance the conflict between approach and defense responses remain unknown. Laboratory mice initially show alternating approach and defense responses toward cockroaches, a natural prey, but with repeated exposure become avid hunters. Here, we used in vivo neural activity recording and cell-type specific manipulations in hunting male mice to identify neurons in the lateral hypothalamus and periaqueductal gray that encode and control predatory approach and defense behaviors. We found a subset of GABAergic neurons in lateral hypothalamus that specifically encoded hunting behaviors and whose stimulation triggered predation but not feeding. This population projects to the periaqueductal gray, and stimulation of these projections promoted predation. Neurons in periaqueductal gray encoded both approach and defensive behaviors but only initially when the mouse showed high levels of fear of the prey. Our findings allow us to propose that GABAergic neurons in lateral hypothalamus facilitate predation in part by suppressing defensive responses to prey encoded in the periaqueductal gray. Our results reveal a neural circuit mechanism for controlling the balance between conflicting approach and defensive behaviors elicited by the same stimulus.

The neuroscience of sugars in taste, gut-reward, feeding circuits, and obesity.

Throughout the animal kingdom sucrose is one of the most palatable and preferred tastants. From an evolutionary perspective, this is not surprising as it is a primary source of energy. However, its overconsumption can result in obesity and an associated cornucopia of maladies, including type 2 diabetes and cardiovascular disease. Here we describe three physiological levels of processing sucrose that are involved in the decision to ingest it: the tongue, gut, and brain. The first section describes the peripheral cellular and molecular mechanisms of sweet taste identification that project to higher brain centers. We argue that stimulation of the tongue with sucrose triggers the formation of three distinct pathways that convey sensory attributes about its quality, palatability, and intensity that results in a perception of sweet taste. We also discuss the coding of sucrose throughout the gustatory pathway. The second section reviews how sucrose, and other palatable foods, interact with the gut-brain axis either through the hepatoportal system and/or vagal pathways in a manner that encodes both the rewarding and of nutritional value of foods. The third section reviews the homeostatic, hedonic, and aversive brain circuits involved in the control of food intake. Finally, we discuss evidence that overconsumption of sugars (or high fat diets) blunts taste perception, the post-ingestive nutritional reward value, and the circuits that control feeding in a manner that can lead to the development of obesity.

The hypothalamus at the crossroads of psychopathology and neurosurgery.

The neurosurgical endeavor to treat psychiatric patients may have been part of human history since its beginning. The modern era of psychosurgery can be traced to the heroic attempts of Gottlieb Burckhardt and Egas Moniz to alleviate mental symptoms through the ablation of restricted areas of the frontal lobes in patients with disabling psychiatric illnesses. Thanks to the adaptation of the stereotactic frame to human patients, the ablation of large volumes of brain tissue has been practically abandoned in favor of controlled interventions with discrete targets. Consonant with the role of the hypothalamus in the mediation of the most fundamental approach-avoidance behaviors, some hypothalamic nuclei and regions, in particular, have been selected as targets for the treatment of aggressiveness (posterior hypothalamus), pathological obesity (lateral or ventromedial nuclei), sexual deviations (ventromedial nucleus), and drug dependence (ventromedial nucleus). Some recent improvements in outcomes may have been due to the use of stereotactically guided deep brain stimulation and the change of therapeutic focus from categorical diagnoses (such as schizophrenia) to dimensional symptoms (such as aggressiveness), which are nonspecific in terms of formal diagnosis. However, agreement has never been reached on 2 related issues: 1) the choice of target, based on individual diagnoses; and 2) reliable prediction of outcomes related to individual targets. Despite the lingering controversies on such critical aspects, the experience of the past decades should pave the way for advances in the field. The current failure of pharmacological treatments in a considerable proportion of patients with chronic disabling mental disorders is reminiscent of the state of affairs that prevailed in the years before the early psychosurgical attempts. This article reviews the functional organization of the hypothalamus, the effects of ablation and stimulation of discrete hypothalamic regions, and the stereotactic targets that have most often been used in the treatment of psychopathological and behavioral symptoms; finally, the implications of current and past experience are presented from the perspective of how this fund of knowledge may usefully contribute to the future of hypothalamic psychosurgery.

Leptin acts via lateral hypothalamic area neurotensin neurons to inhibit orexin neurons by multiple GABA-independent mechanisms.

The adipocyte-derived hormone leptin modulates neural systems appropriately for the status of body energy stores. Leptin inhibits lateral hypothalamic area (LHA) orexin (OX; also known as hypocretin)-producing neurons, which control feeding, activity, and energy expenditure, among other parameters. Our previous results suggest that GABAergic LHA leptin receptor (LepRb)-containing and neurotensin (Nts)-containing (LepRb(Nts)) neurons lie in close apposition with OX neurons and control Ox mRNA expression. Here, we show that, similar to leptin, activation of LHA Nts neurons by the excitatory hM3Dq DREADD (designer receptor exclusively activated by designer drugs) hyperpolarizes membrane potential and suppresses action potential firing in OX neurons in mouse hypothalamic slices. Furthermore, ablation of LepRb from Nts neurons abrogated the leptin-mediated inhibition, demonstrating that LepRb(Nts) neurons mediate the inhibition of OX neurons by leptin. Leptin did not significantly enhance GABAA-mediated inhibitory synaptic transmission, and GABA receptor antagonists did not block leptin-mediated inhibition of OX neuron activity. Rather, leptin diminished the frequency of spontaneous EPSCs onto OX neurons. Furthermore, leptin indirectly activated an ATP-sensitive potassium (K(ATP)) channel in OX neurons, which was required for the hyperpolarization of OX neurons by leptin. Although Nts did not alter OX activity, galanin, which is coexpressed in LepRb(Nts) neurons, inhibited OX neurons, whereas the galanin receptor antagonist M40 (galanin-(1-12)-Pro3-(Ala-Leu)2-Ala amide) prevented the leptin-induced hyperpolarization of OX cells. These findings demonstrate that leptin indirectly inhibits OX neurons by acting on LHA LepRb(Nts) neurons to mediate two distinct GABA-independent mechanisms of inhibition: the presynaptic inhibition of excitatory neurotransmission and the opening of K(ATP) channels.

Sex differences in circadian timing systems: implications for disease.

Virtually every eukaryotic cell has an endogenous circadian clock and a biological sex. These cell-based clocks have been conceptualized as oscillators whose phase can be reset by internal signals such as hormones, and external cues such as light. The present review highlights the inter-relationship between circadian clocks and sex differences. In mammals, the suprachiasmatic nucleus (SCN) serves as a master clock synchronizing the phase of clocks throughout the body. Gonadal steroid receptors are expressed in almost every site that receives direct SCN input. Here we review sex differences in the circadian timing system in the hypothalamic-pituitary-gonadal axis (HPG), the hypothalamic-adrenal-pituitary (HPA) axis, and sleep-arousal systems. We also point to ways in which disruption of circadian rhythms within these systems differs in the sexes and is associated with dysfunction and disease. Understanding sex differentiated circadian timing systems can lead to improved treatment strategies for these conditions.

Deep brain stimulation for obesity: past, present, and future targets.

The authors review the history of deep brain stimulation (DBS) in patients for treating obesity, describe current DBS targets in the brain, and discuss potential DBS targets and nontraditional stimulation parameters that may improve the effectiveness of DBS for ameliorating obesity. Deep brain stimulation for treating obesity has been performed both in animals and in humans with intriguing preliminary results. The brain is an attractive target for addressing obesity because modulating brain activity may permit influencing both sides of the energy equation--caloric intake and energy expenditure.

Disability from cardiovascular diseases at Osh city, Kyrgyz Republic.

Cardiovascular diseases (CVDs) are the leading global cause of death, contributing to health deterioration and increased healthcare expenses. Therefore, it is of interest to investigate the disability rates related to cardiovascular diseases at Osh city, Kyrgyz Republic. We report the prevalence of disability in both urban and rural areas, highlighting the impact of regional disparities in medical and social services. Data shows that adult cardiovascular disease impairment in Kyrgyzstan suggests challenges in accessing medical and social support, particularly in rural regions. Thus, the rural-urban divide in critical disability metrics impedes equitable research. Comprehensive assessments and interventions are imperative to mitigate cardiovascular diseases and associated disabilities in both rural and urban populations at Kyrgyz Republic.

Ghrelin's orexigenic action in the lateral hypothalamic area involves indirect recruitment of orexin neurons and arcuate nucleus activation.

OBJECTIVE: Ghrelin is a potent orexigenic hormone, and the lateral hypothalamic area (LHA) has been suggested as a putative target mediating ghrelin's effects on food intake. Here, we aimed to investigate the presence of neurons expressing ghrelin receptor (a.k.a. growth hormone secretagogue receptor, GHSR) in the mouse LHA (LHAGHSR neurons), its physiological implications and the neuronal circuit recruited by local ghrelin action. METHODS: We investigated the distribution of LHAGHSR neurons using different histologic strategies, including the use of a reporter mice expressing enhanced green fluorescent protein under the control of the GHSR promoter. Also, we investigated the physiological implications of local injections of ghrelin within the LHA, and the extent to which the orexigenic effect of intra-LHA-injected ghrelin involves the arcuate nucleus (ARH) and orexin neurons of the LHA (LHAorexin neurons) RESULTS: We found that: 1) LHAGHSR neurons are homogeneously distributed throughout the entire LHA; 2) intra-LHA injections of ghrelin transiently increase food intake and locomotor activity; 3) ghrelin's orexigenic effect in the LHA involves the indirect recruitment of LHAorexin neurons and the activation of ARH neurons; and 4) LHAGHSR neurons are not targeted by plasma ghrelin. CONCLUSIONS: We provide a compelling neuroanatomical and functional characterization of LHAGHSR neurons in male mice that indicates that LHAGHSR cells are part of a hypothalamic neuronal circuit that potently induces food intake.

Replaced Segment 6 Artery From the Gastroduodenal Artery: A Challenging and Rare Anatomical Variation of Hepatic Artery in Pancreaticoduodenectomy.

Variations in the hepatic artery's anatomy can significantly impact planning and executing pancreatic and hepatobiliary surgeries. Of these, the commonest are variations of right and left hepatic arteries originating from superior mesenteric and left gastric arteries, respectively. The anomalous origin of the right hepatic artery from the gastroduodenal artery (GDA) is among the rarest and most challenging anatomy, especially in patients undergoing pancreatoduodenectomy (PD) since GDA ligation is a mandatory step, which may threaten the liver blood supply. We present a 62-year-old male with suspected distal cholangiocarcinoma and plan a robot-assisted pancreatoduodenectomy. Preoperative computed tomography evaluation revealed an anomalous segment 6 artery arising from the GDA and coursing posterolaterally to the common bile duct in the hepatoduodenal ligament. Also, the patient had a replacement left hepatic artery originating from the left gastric artery. The described vascular anomaly has not been previously reported in patients undergoing PD. Awareness of vascular anomalies is the key to performing oncologically radical surgery without increasing bleeding and ischemic complications in patients undergoing complex procedures like PD.

Hypocretin role in posttraumatic stress disorder-like behaviors induced by a novel stress protocol in mice.

Introduction: Posttraumatic stress disorder (PTSD) is a psychiatric disorder developed in individuals who expose to traumatic events. These patients may experience symptoms, such as recurrent unwanted memory of the traumatic event, avoidance of reminders of the trauma, increased arousal, and cognitive difficulty. The hypocretinergic system originates from the lateral hypothalamic area (LHA) and projects diffusely to the whole brain, and hypocretin may be involved in the features of stress-related disorder, PTSD. Methods: Our study aimed to investigate the role of basolateral amygdala (BLA) hypocretin signals in the pathophysiology of PTSD-like symptoms induced by the modified multiple-prolonged stress (MPS) protocol. The BLA, a brain region involved in fear-related behaviors, receives the hypocretin projections. In this study, TCS1102, a dual hypocretin receptor antagonist, was used to block the hypocretin signal in BLA. Results: Our data indicated that the MPS protocol is a potential PTSD-like paradigm in mice. Meanwhile, the blockade of hypocretin signaling in the BLA relieved the MPS-induced fear response, and partially reduced PTSD-like anxiety behaviors performed by the open field test (OFT) and elevated plus maze (EPM) task. Discussion: Our findings suggest that the hypocretinergic system is a potential therapeutic approach for PTSD treatment. With further research, the hypocretin-based medication can be a candidate for human PTSD treatment.

Assessment of the Benefit of a Deep Cleansing Gel Containing Salicylic Acid 2%, Zinc Gluconate 0.2% and Lipohydroxy Acids 0.05% in Patients with Mild to Moderate Truncal Acne: Results from an Exploratory Study.

Purpose: Acne is a skin condition of the pilosebaceous unit that affects mainly the face, chest and trunk. Approximately 50% of subjects with facial acne also have acne of the trunk. This study investigated the clinical benefit of a cleansing gel containing salicylic acid 2%, zinc gluconate 0.2% and lipohydroxy acid 0.05% in truncal acne after 84 days of daily use. Materials and Methods: A single center, open label, non-randomized study with 51 subjects with mild to moderate truncal acne was conducted. Thirty-five (35) subjects completed the study; mean age was 23 years. Inflammatory and non-inflammatory lesions, Transepidermal water loss (TEWL) and local tolerance were assessed at baseline, Day 42 and Day 84 and total lesion count was calculated. Results: The total lesion count was significantly reduced (p<0.05) after 42 days (-21.5%) and 84 days (-56.3%). Non-inflammatory lesions were significantly decreased after 84 days (-64.0%) only, while inflammatory lesions were decreased at Day 42 (-29.2%), and Day 84 (-48.2%). A statistically significant skin barrier improvement was observed at Day 84 (-21.26%). No adverse events or relevant local intolerance were reported. Conclusion: The use of the cleansing gel studied was effective in improving mild to moderate truncal acne and contributed to the skin barrier improvement. The product was well tolerated. Clintrial Data Base Identifier: NCT05584150.

Effects of Luteinizing Hormone Releasing Hormone A2 on Gonad Development in Juvenile Amur Sturgeon, Acipenser schrenckii, Revealed by Transcriptome Profiling Analysis.

Acipenser schrenckii is an economically important aquatic species whose gonads require particularly long times to reach sexual maturity. Luteinizing hormone plays important roles in gonad development, and luteinizing hormone releasing hormone A2 (LH-A2) is used as an oxytocin to promote ovulation in aquaculture of A. schrenckii. In this study, we aimed to determine the effects of LH-A2 on gonad development in juvenile A. schrenckii through transcriptome profiling analysis of the pituitary and gonads after LH-A2 treatment at a dose of 3 µg/kg. The 17ß-estradiol (E2) levels gradually increased with LH-A2 treatment time, and significantly differed from those of the control group on days 5 and 7 (p < 0.01). However, the content of testosterone (Testo) gradually decreased with LH-A2 treatment time and showed significant differences on day 3 (p < 0.05), and on days 5 and 7 (p < 0.01), compared to those in the control group. Thus, LH-A2 promotes the secretion of E2 and inhibits the secretion of Testo. Transcriptome profiling analysis revealed a total of 2,883 and 8,476 differentially expressed genes (DEGs) in the pituitary and gonads, respectively, thus indicating that LH-A2 has more regulatory effects on the gonads than the pituitary in A. schrenckii. Signal transduction, global and overview maps, immune system, endocrine system and lipid metabolism were the main enriched metabolic pathways in both the pituitary and gonads. Sixteen important genes were selected from these metabolic pathways. Seven genes were co-DEGs enriched in both signal transduction and endocrine system metabolic pathways. The other co-DEGs were selected from the immune system and lipid metabolism metabolic pathways, and showed mRNA expression changes of >7.0. The expression of five DEGs throughout LH-A2 treatment was verified to show the same patterns of change as those observed with RNA-seq, indicating the accuracy of the RNA-seq in this study. Our findings provide valuable evidence of the regulation of gonad development of juvenile A. schrenckii by LH-A2 and may enable the establishment of artificial techniques to regulate gonad development in this species.

From Molecule to Behavior: Hypocretin/orexin Revisited From a Sex-dependent Perspective.

The hypocretin/orexin (Hcrt/Orx) system in the perifornical lateral hypothalamus has been recognized as a critical node in a complex network of neuronal systems controlling both physiology and behavior in vertebrates. Our understanding of the Hcrt/Orx system and its array of functions and actions has grown exponentially in merely 2 decades. This review will examine the latest progress in discerning the roles played by the Hcrt/Orx system in regulating homeostatic functions and in executing instinctive and learned behaviors. Furthermore, the gaps that currently exist in our knowledge of sex-related differences in this field of study are discussed.

Time to drink: Activating lateral hypothalamic area neurotensin neurons promotes intake of fluid over food in a time-dependent manner.

The lateral hypothalamic area (LHA) is essential for ingestive behavior but has primarily been studied in modulating feeding, with comparatively scant attention on drinking. This is partly because most LHA neurons simultaneously promote feeding and drinking, suggesting that ingestive behaviors track together. A notable exception are LHA neurons expressing neurotensin (LHANts neurons): activating these neurons promotes water intake but modestly restrains feeding. Here we investigated the connectivity of LHANts neurons, their necessity and sufficiency for drinking and feeding, and how timing and resource availability influence their modulation of these behaviors. LHANts neurons project broadly throughout the brain, including to the lateral preoptic area (LPO), a brain region implicated in modulating drinking behavior. LHANts neurons also receive inputs from brain regions implicated in sensing hydration and energy status. While activation of LHANts neurons is not required to maintain homeostatic water or food intake, it selectively promotes drinking during the light cycle, when ingestive drive is low. Activating LHANts neurons during this period also increases willingness to work for water or palatable fluids, regardless of their caloric content. By contrast, LHANts neuronal activation during the dark cycle does not promote drinking, but suppresses feeding during this time. Finally, we demonstrate that the activation of the LHANts â†’ LPO projection is sufficient to mediate drinking behavior, but does not suppress feeding as observed after generally activating all LHANts neurons. Overall, our work suggests how and when LHANts neurons oppositely modulate ingestive behaviors.

A single allele of the hsa-miR-302/367 cluster maintains human pluripotent stem cells.

Introduction: In a diploid organism, two alleles from a single genetic locus are expressed to generate a normal phenotype. Heterozygous deleterious mutation causes a reduction of functional proteins to a half dose and insufficient amounts of functional proteins can occur to generate an in-normal phenotype, namely haploinsufficiency. Heterozygous deleterious mutation of microRNAs (miRs), non-coding RNAs that regulate the expression level of target transcripts, is still not well understood. The hsa-miR-302/367 cluster is the most abundant and specifically up-regulated miR cluster in human embryonic stem cells (ESCs) and induced pluripotent stem cells (iPSCs) and plays an important role in the maintenance of pluripotency. Methods: We targeted the hsa-miR-302/367 region via a Cas9 nuclease complex with guide RNA and replaced that region with green fluorescent protein (GFP). Using a homologous donor, consisting of left and right arms and GFP, we confirmed deletion of the hsa-miR-302/367 cluster by homologous recombination without cellular destruction by microscopy. We sub-cloned GFP-positive colonies and checked the genotype of each sub-clone by genomic PCR. We then analyzed the pluripotency of heterozygous knockout cells with a hsa-miR-302/367 cluster by assessing cell proliferation ratio, morphology, and undifferentiated marker gene expression. We also used an embryoid body formation assay and transplanted wild-type and heterozygous knockout cells into immune-deficient mice. Furthermore, to analyze the lineage-specific differentiation potential of heterozygous knockout cells, we differentiated both wild-type and heterozygous knockout cells into neural stem cells. Results: Here, we show that the half dose of mature miRs from the hsa-miR-302/367 cluster loci was sufficient for the continued self-renewal of hiPSCs. All GFP-positive clones were revealed to be heterozygous knockout cells, suggesting hsa-miR-302/367 cluster homozygous knockout cells were not maintained. The cell proliferation ratio, morphology, and expression of undifferentiated marker genes were comparable between wild-type and heterozygous knockout of undifferentiated human iPSCs. In addition, we found that heterozygous knockout human iPSCs have the capacity to differentiate into three germ layers, including neural stem cells. Conclusions: Taken together, a single allele of the hsa-miR-302/367 cluster expresses a sufficient amount of miRs to maintain the pluripotent properties of human stem cells.

Establishing novel roles of bifidocin LHA, antibacterial, antibiofilm and immunomodulator against Pseudomonas aeruginosa corneal infection model.

Bifidocin LHA, a novel bacteriocin, was extracted from bee honey B. adolescentis and purified. Bifidocin LHA was characterized as a protein in nature, without lipid or carbohydrate moieties, the molecular weight was 16,000 Da protein, heat-stable and active at a wide range of pH values, bactericidal effect, detergent, and solvents did not affect bifidocin activity and can be classified as type II bacteriocin. In vitro, the antibacterial activity of purified bifidocin LHA was significantly higher than crude bifidocin LHA (P < 0.05) against Pseudomonas aeruginosa (P. aeruginosa). The antibiofilm activity of bifidocin LHA was significantly higher than the antibiofilm activity of Amikacin (P < 0.05). In vivo, bifidocin LHA demonstrates a significant decreased in the number of P. aeruginosa in the eye, while complete clearance of P. aeruginosa comparing with the control (P < 0.05) when treating with Bifidobacterium adolescentis and bifidocin LHA together. Bifidobacterium adolescentis and bifidocin LHA treatment together induced substantial elevation of IL10 and IL-12 concentrations (P < 0.01) that helped to prevent damage caused by the inflammatory response. Succeeded to eradicate P. aeruginosa infection improved by histological patterns of the eye tissues. This study indicated Bifidobacterium adolescentis and bifidocin LHA consider as crucial strategies for the practical treatment of eye infection in the future.

Ontogeny of the Projections From the Dorsomedial Division of the Anterior Bed Nucleus of the Stria Terminalis to Hypothalamic Nuclei.

The bed nucleus of the stria terminalis (BNST) is a telencephalic structure well-connected to hypothalamic regions known to control goal-oriented behaviors such as feeding. In particular, we showed that the dorsomedial division of the anterior BNST innervate neurons of the paraventricular (PVH), dorsomedial (DMH), and arcuate (ARH) hypothalamic nuclei as well as the lateral hypothalamic area (LHA). While the anatomy of these projections has been characterized in mice, their ontogeny has not been studied. In this study, we used the DiI-based tract tracing approach to study the development of BNST projections innervating several hypothalamic areas including the PVH, DMH, ARH, and LHA. These results indicate that projections from the dorsomedial division of the anterior BNST to hypothalamic nuclei are immature at birth and substantially reach the PVH, DMH, and the LHA at P10. In the ARH, only sparse fibers are observed at P10, but their density increased markedly between P12 and P14. Collectively, these findings provide new insight into the ontogeny of hypothalamic circuits, and highlight the importance of considering the developmental context as a direct modulator in their proper formation.

Prevention of cisplatin-induced nausea and vomiting by seabuckthorn (Hippophae rhamnoides L.) seed oil: Insights at the level of orexin-A in rats.

OBJECTIVES: Nausea and vomiting are perennial problems in cancer patients undergoing chemotherapy. Orexin-A (OXA) has been shown to regulate feeding and gastric motility. Seabuckthorn (Hippophae rhamnoides L.) seed oil (SSO) has been proved to promote digestion and bowel movements. We investigated whether SSO alleviated cisplatin-induced vomiting and its possible mechanism involved in OXA. MATERIALS AND METHODS: Rats were randomly divided into normal control group (NCG), cisplatin group (CG), SSO low-dose group (SLG), SSO middle-dose group (SMG) SSO high-dose group (SHG), and ondansetron group (OG). Rats were pretreated respectively with SSO (0.850, 1.675, and 3.350 g/kg·BW) and ondansetron (2 mg/kg·BW) in SLG, SMG, SHG, and OG for 6 days, and the same volume of saline in NCG and CG groups. On the 6th day, cisplatin (6 mg/kg, IP) was administered in all groups except NCG. The cumulative food and kaolin intake, gastric emptying, plasma OXA level, OX1R mRNA and protein expression in the hypothalamus and brainstem, and OXA expression in the lateral hypothalamic area (LHA) were observed, and the HPLC method was used to analyze the composition of SSO. RESULTS: Kaolin intake in cisplatin-induced vomiting rats was significantly reduced (P<0.05) and gastric emptying delayed by cisplatin was improved (P<0.05-0.01) by pretreatment with SSO. Plasma OXA concentration, OX1R expression in the hypothalamus and brainstem increased significantly (P<0.05-0.01). Furthermore, OXA expression in LHA also increased significantly (P<0.05). CONCLUSION: SSO prevents cisplatin-induced vomiting in rats, which is possibly involved in increasing peripheral and central OXA and the expression of OX1R in the hypothalamus and brainstem.

Phonological processing in psychopathic offenders.

Recent research has demonstrated that psychopathic offenders exhibit dynamic cognitive and behavioral deficits on a variety of lab tasks that differentially activate left hemisphere resources. The Left Hemisphere Activation (LHA) hypothesis is a cognitive perspective that aims to address these deficits by conceptualizing psychopathy as a disorder in which behavior and cognitive processing change dynamically as a function of the differential taxation of left hemisphere resources. This study aimed to investigate whether psychopathic traits are associated with electrophysiological anomalies under conditions that place differential demands on left hemisphere language processing systems. We examined in a sample of 43 incarcerated indivdiuals the evocation of the N320, an event-related potential (ERP) elicited by nontarget stimuli during a phonological/phonetic decision task that has been shown to elicit greater activation and cognitive processing within the left hemisphere than the right hemisphere. Findings for a subsample of 18 offenders low in psychopathic traits were generally consistent with previous findings in healthy individuals, suggesting similar electrophysiological activity during phonological processing. However, psychopathic traits impacted the amplitude of the N320. Higher levels of psychopathic traits were associated with reduced left-lateralization in phonological processing as well as enhanced ERP differentiation between pronounceable and nonpronounceable stimuli. These findings provide physiological evidence of a relationship between psychopathic traits and anomalous language processing at the phonological level of word processing.

Lateral Hypothalamic GABAergic Neurons Encode and Potentiate Sucrose's Palatability.

Sucrose is attractive to most species in the animal kingdom, not only because it induces a sweet taste sensation but also for its positive palatability (i.e., oromotor responses elicited by increasing sucrose concentrations). Although palatability is such an important sensory attribute, it is currently unknown which cell types encode and modulate sucrose's palatability. Studies in mice have shown that activation of GABAergic LHAVgat+ neurons evokes voracious eating; however, it is not known whether these neurons would be driving consumption by increasing palatability. Using optrode recordings, we measured sucrose's palatability while VGAT-ChR2 transgenic mice performed a brief access sucrose test. We found that a subpopulation of LHAVgat+ neurons encodes palatability by increasing (or decreasing) their activity as a function of the increment in licking responses evoked by sucrose concentrations. Optogenetic gain of function experiments, where mice were able to choose among available water, 3% and 18% sucrose solutions, uncovered that opto-stimulation of LHAVgat+ neurons consistently promoted higher intake of the most palatable stimulus (18% sucrose). In contrast, if they self-stimulated near the less palatable stimulus, some VGAT-ChR2 mice preferred water over 18% sucrose. Unexpectedly, activation of LHAVgat+ neurons increased quinine intake but only during water deprivation, since in sated animals, they failed to promote quinine intake or tolerate an aversive stimulus. Conversely, these neurons promoted overconsumption of sucrose when it was the nearest stimulus. Also, experiments with solid foods further confirmed that these neurons increased food interaction time with the most palatable food available. We conclude that LHAVgat+ neurons increase the drive to consume, but it is potentiated by the palatability and proximity of the tastant.