Evaluation of Foetal Haemoglobin Status among Nigerian Patients with Sickle Cell Anaemia Using High Performance Liquid Chromatography.

BACKGROUND: Sickle cell anaemia (SCA, HbSS) is a genetic disorder of haemoglobin with marked variation in clinical manifestation. The aim of this study was to determine the foetal haemoglobin (HbF) status of patients with HbSS, compared with that of individuals with HbAS and HbAA control as well as to establish the relationship between HbF level and age and gender of the participants. METHODS: This was a cross-sectional study in which HbF values of known HbSS patients along with HbAS and HbAA controls were analysed using High Performance Liquid Chromatography. Socio-demographic and other information were obtained with the use of questionnaire. Data was analyzed using SPSS software, version 20.0. Ethical approval was obtained for the study. RESULTS: One hundred and two (102) participants were recruited for the study, comprising 60 patients with HbSS, 22 HbAS and 20 HbAA controls, with mean age of 11.0 years±9.6, 11.7 years ±8.8 and 12.3 years±8.1 respectively. There were 30 (61.2%) males and 30 (56.6%) females for HbSS group, 9 (18.4%) males and 13(24.5%) females for HbAS group and 10(20.4%) males and 10(18.9%) for HbAA group. Mean HbF level among HbSS participants was 8.0 ±6.1% and was significantly higher than that of HbAS (3.0 ±3.4%) and HbAA (2.2 ±4.1%) control (P<0.05). Mean HbF level was higher in children (<18 years) than adults (e"18 years) among HbSS, HbAS and HbAA participants, though not statistically significant (p >0.05). Mean HbF level was also higher among female HbSS, HbAS and HbAA groups compared to corresponding male groups, though only HbSS female group was significant (p = 0.031). CONCLUSION: Patients with HbSS have significantly higher HbF level than individuals with HbAS and HbAA. Foetal haemoglobin level tend to decrease with advancing age and higher in females. Increased HbF level may play a compensatory mechanism in sickling in HbSS, thus the use of agent that increase HbF level may improve clinical outcome.

CONTEXTE: L'anémie falciforme (SCA, HbSS) est un mal de l'hémoglobine avec une variation marquée de la manifestation. Le but de cette étude était de déterminer le fœtus le statut d'hémoglobine (HbF) des patients atteints d'HbSS, par rapport à celle des personnes ayant un contrôle de l'HbAS et de l'HbAA ainsi que établir la relation entre le taux d'HbF et l'âge et le sexe des participants. MÉTHODES: Il s'agissait d'une étude transversale dans laquelle l'HbF valeurs des patients HbSS connus ainsi que l'HbAS et l'HbAA les contrôles ont été analysés à l'aide d'un liquide haute performance Chromatographie. Informations sociodémographiques et autres ont été obtenus à l'aide d'un questionnaire. Les données ont été analysées à l'aide du logiciel SPSS, version 20.0. L'approbation éthique a été obtenue pour l'étude. RÉSULTATS: Cent deux (102) participants ont été recrutés pour l'étude, comprenant 60 patients avec HbSS, 22 HbAS et 20 contrôles HbAA, avec un âge moyen de 11,0 ans ± 9,6, 11,7 ans ± 8,8 et 12,3 ans ± 8,1 respectivement. Il y avait 30 (61,2%) hommes et 30 femmes (56,6%) pour le groupe HbSS, 9 hommes (18,4%) et 13 femmes (24,5%) pour le groupe HbAS et 10 hommes (20,4%) et 10 (18,9%) pour le groupe HbAA. Niveau moyen d'HbF parmi l'HbSS participants était de 8,0 ± 6,1% et était significativement plus élevé que celle du contrôle HbAS (3,0 ± 3,4%) et HbAA (2,2 ± 4,1%) (p <0,05). Le taux moyen d'HbF était plus élevé chez les enfants (<18 ans) que chez les adultes (e "18 ans) chez les participants HbSS, HbAS et HbAA, cependant non statistiquement significatif (p> 0,05). Le taux moyen d'HbF était également plus élevé parmi les groupes féminins HbSS, HbAS et HbAA par rapport aux groupes masculins correspondants, mais seulement au groupe féminin HbSS était significative (p = 0,031). CONCLUSION: Les patients atteints d'HbSS ont des Taux d'HbF que les individus avec HbAS et HbAA. Fœtal le taux d'hémoglobine a tendance à diminuer avec l'âge et plus élevé chez les femmes. L'augmentation du niveau d'HbF peut jouer un rôle compensatoire mécanisme de la faucille dans l'HbSS, donc l'utilisation d'un agent qui l'augmentation du taux d'HbF peut améliorer les résultats cliniques. Mots clés: hémoglobine fœtale, liquide haute performance Chromatographie, drépanocytose, traits drépanocytaires, normaux l'hémoglobine adulte.

Integrative STEM education for undergraduate neuroscience: Design and implementation.

As an integrative discipline, neuroscience can serve as a vehicle for the development of integrative thinking skills and broad-based scientific proficiency in undergraduate students. Undergraduate neuroscience curricula incorporate fundamental concepts from multiple disciplines. Deepening the explicit exploration of these connections in a neuroscience core curriculum has the potential to support more meaningful and successful undergraduate STEM learning for neuroscience students. Curriculum and faculty development activities related to an integrative core curriculum can provide opportunities for faculty across disciplines and departments to advance common goals of inclusive excellence in STEM. These efforts facilitate analysis of the institutional STEM curriculum from the student perspective, and assist in creating an internal locus of accountability for diversity, equity, and inclusion within the institution. Faculty at the College of the Holy Cross have undertaken the collaborative design and implementation of an integrative core curriculum for neuroscience that embraces principles of inclusive pedagogy, emphasizes the connections between neuroscience and other disciplines, and guides students to develop broad proficiency in fundamental STEM concepts and skills.

An Integrative Approach to STEM Concepts in an Introductory Neuroscience Course: Gains in Interdisciplinary Awareness.

Neuroscience is an integrative discipline for which students must achieve broad-based proficiency in many of the sciences. We are motivated by the premise that student pursuit of proficiency in science, technology, engineering, and mathematics (STEM) can be supported by awareness of the application of knowledge and tools from the various disciplines for solving complex problems. We refer to this awareness as "interdisciplinary awareness." Faculty from biology, chemistry, mathematics/computer science, physics, and psychology departments contributed to a novel integrative introductory neuroscience course with no pre-requisites. STEM concepts were taught in "flipped" class modules throughout the semester: Students viewed brief videos and completed accompanying homework assignments independently. In subsequent class meetings, students applied the STEM concepts to understand nervous system structure and function through engaged learning activities. The integrative introduction to neuroscience course was compared to two other courses to test the hypothesis that it would lead to greater gains in interdisciplinary awareness than courses that overlap in content but were not designed for this specific goal. Data on interdisciplinary awareness were collected using previously published tools at the beginning and end of each course, enabling within-subject analyses. Students in the integrative course significantly increased their identification of scientific terms as relevant to neuroscience in a term-discipline relevance survey and increased their use of terms related to levels of analysis (e.g., molecular, cellular, systems) in response to an open-ended prompt. These gains were seen over time within the integrative introduction to neuroscience course as well as relative to the other two courses.

Taking Care of Relationships in the Intensive Care Unit: Positive Impact on Family Consent for Organ Donation.

BACKGROUND: Organ donation refusal from relatives of potential donors with brain death significantly reduces organ availability. The need for organ donation has increased over time, but the shortage of available donors is the major limiting factor in transplantation. We analyzed the impact of a new systematic communication approach between medical staff and patients' relatives on the rate of consent to organ donation. METHODS: The study was conducted as a single-center, non-randomized, controlled, before-and-after study at an 18-bed intensive care unit (ICU) of a university hospital. We compared the rate of consent for organ donation before and after the introduction of the new communication approach. RESULTS: A total of 291 brain-dead patients were studied. The consent rate increased from 71% in the pre-intervention period (2007-2012) to 78.4% in the post-intervention period (2013-2015), with an 82.75% increase in the 2014 to 2015 period. During these periods, no significant variation of consent to organ donation was recorded at the national and regional levels. CONCLUSIONS: The introduction of a new communication approach between medical staff and relatives of brain-dead patients was associated with a significant increase in the rate of consent to donation. Our results highlight the importance of empathy with relatives in the ICU.

Endogenous co-agonists of the NMDA receptor modulate contextual fear in trace conditioning.

We have used mutant mice to probe the roles of the endogenous co-agonists of the NMDA receptor (NMDAR), D-serine and glycine, in fear learning and memory. Serine racemase knockout (SR-/-) mice have less than 15% of wild type forebrain levels of D-serine, whereas glycine transporter 1 heterozygous knockout (GlyT1+/-) mice have elevated synaptic glycine. While cued fear was normal in both delay and trace conditioned mice of both mutant genotypes, contextual fear was affected in trace conditioned subjects: SR-/- mice showed decreased contextual freezing, whereas GlyT1+/- mice showed elevated contextual freezing. These results indicate that endogenous co-agonists of the NMDAR modulate the conditioning of contextual fear responses, particularly in trace conditioning. They further suggest that endogenous glycine can compensate for the D-serine deficiency in cued and contextual fear following delay conditioning.

Effects of environmental enrichment on anxiety-like behavior, sociability, sensory gating, and spatial learning in male and female C57BL/6J mice.

The influence of housing on cognition and emotional regulation in mice presents a problem for the study of genetic and environmental risk factors for neuropsychiatric disorders: standard laboratory housing may result in low levels of cognitive function or altered levels of anxiety that leave little room for assessment of deleterious effects of experimental manipulations. The use of enriched environment (EE) may allow for the measurement of a wider range of performance in cognitive domains. Cognitive and behavioral effects of EE in male mice have not been widely reproduced, perhaps due to variability in the application of enrichment protocols, and the effects of EE in female mice have not been widely studied. We have developed an EE protocol using common laboratory equipment that, without a running wheel for exercise, results in significant cognitive and behavioral effects relative to standard laboratory housing conditions. We compared male and female wild-type C57BL/6J mice reared from weaning age in an EE to those reared in a standard environment (SE), using common measures of anxiety-like behavior, sensory gating, sociability, and spatial learning and memory. Sex was a significant factor in relevant elevated plus maze (EPM) measures, and bordered on significance in a social interaction (SI) assay. Effects of EE on anxiety-like behavior and sociability were indicative of a general increase in exploratory activity. In male and female mice, EE resulted in reduced prepulse inhibition (PPI) of the acoustic startle response, and enhanced spatial learning and use of spatially precise strategies in a Morris water maze task.

Multiple risk pathways for schizophrenia converge in serine racemase knockout mice, a mouse model of NMDA receptor hypofunction.

Schizophrenia is characterized by reduced hippocampal volume, decreased dendritic spine density, altered neuroplasticity signaling pathways, and cognitive deficits associated with impaired hippocampal function. We sought to determine whether this diverse pathology could be linked to NMDA receptor (NMDAR) hypofunction, and thus used the serine racemase-null mutant mouse (SR(-/-)), which has less than 10% of normal brain D-serine, an NMDAR coagonist. We found that D-serine was necessary for the maintenance of long-term potentiation in the adult hippocampal dentate gyrus and for full NMDAR activity on granule cells. SR(-/-) mice had reduced dendritic spines and hippocampal volume. These morphological changes were paralleled by diminished BDNF/Akt/mammalian target of rapamycin (mTOR) signaling and impaired performance on a trace-conditioning memory task. Chronic D-serine treatment normalized the electrophysiological, neurochemical, and cognitive deficits in SR(-/-) mice. These results demonstrate that NMDAR hypofunction can reproduce the numerous hippocampal deficits associated with schizophrenia, which can be reversed by chronic peripheral D-serine treatment.

Time-dependent effects of haloperidol on glutamine and GABA homeostasis and astrocyte activity in the rat brain.

RATIONALE: Schizophrenia is a severe, persistent, and fairly common mental illness. Haloperidol is widely used and is effective against the symptoms of psychosis seen in schizophrenia. Chronic oral haloperidol administration decreased the number of astrocytes in the parietal cortex of macaque monkeys (Konopaske et al., Biol Psych 63:759-765, 2008). Since astrocytes play a key role in glutamate metabolism, chronic haloperidol administration was hypothesized to modulate astrocyte metabolic function and glutamate homeostasis. OBJECTIVES: This study investigated the effects of chronic haloperidol administration on astrocyte metabolic activity and glutamate, glutamine, and GABA homeostasis. METHODS: We used ex vivo ¹³C magnetic resonance spectroscopy along with high-performance liquid chromatography after [1-¹³C]glucose and [1,2-¹³C]acetate administration to analyze forebrain tissue from rats administered oral haloperidol for 1 or 6 months. RESULTS: Administration of haloperidol for 1 month produced no changes in ¹³C labeling of glutamate, glutamine, or GABA, or in their total levels. However, a 6-month haloperidol administration increased ¹³C labeling of glutamine by [1,2-¹³C]acetate. Moreover, total GABA levels were also increased. Haloperidol administration also increased the acetate/glucose utilization ratio for glutamine in the 6-month cohort. CONCLUSIONS: Chronic haloperidol administration in rats appears to increase forebrain GABA production along with astrocyte metabolic activity. Studies exploring these processes in subjects with schizophrenia should take into account the potential confounding effects of antipsychotic medication treatment.

Identity of endogenous NMDAR glycine site agonist in amygdala is determined by synaptic activity level.

Mechanisms of N-methyl-D-aspartate receptor-dependent synaptic plasticity contribute to the acquisition and retention of conditioned fear memory. However, synaptic rules which may determine the extent of N-methyl-D-aspartate receptor activation in the amygdala, a key structure implicated in fear learning, remain unknown. Here we show that the identity of the N-methyl-D-aspartate receptor glycine site agonist at synapses in the lateral nucleus of the amygdala may depend on the level of synaptic activation. Tonic activation of N-methyl-D-aspartate receptors at synapses in the amygdala under low activity conditions is supported by ambient D-serine, whereas glycine may be released from astrocytes in response to afferent impulses. The release of glycine may decode the increases in afferent activity levels into enhanced N-methyl-D-aspartate receptor-mediated synaptic events, serving an essential function in the induction of N-methyl-D-aspartate receptor-dependent long-term potentiation in fear conditioning pathways.

Cell selective conditional null mutations of serine racemase demonstrate a predominate localization in cortical glutamatergic neurons.

D-serine, which is synthesized by the enzyme serine racemase (SR), is a co-agonist at the N-methyl-D-aspartate receptor (NMDAR). Crucial to an understanding of the signaling functions of D-serine is defining the sites responsible for its synthesis and release. In order to quantify the contributions of astrocytes and neurons to SR and D-serine localization, we used recombinant DNA techniques to effect cell type selective suppression of SR expression in astrocytes (aSRCKO) and in forebrain glutamatergic neurons (nSRCKO). The majority of SR is expressed in neurons: SR expression was reduced by ~65% in nSRCKO cerebral cortex and hippocampus, but only ~15% in aSRCKO as quantified by western blots. In contrast, nSRCKO is associated with only modest decreases in D-serine levels as quantified by HPLC, whereas D-serine levels were unaffected in aSRCKO mice. Liver expression of SR was increased by 35% in the nSRCKO, suggesting a role for peripheral SR in the maintenance of brain D-serine. Electrophysiologic studies of long-term potentiation (LTP) at the Schaffer collateral-CA1 pyramidal neuron synapse revealed no alterations in the aSRCKO mice versus wild-type. LTP induced by a single tetanic stimulus was reduced by nearly 70% in the nSRCKO mice. Furthermore, the mini-excitatory post-synaptic currents mediated by NMDA receptors but not by AMPA receptors were significantly reduced in nSRCKO mice. Our findings indicate that in forebrain, where D-serine appears to be the endogenous co-agonist at NMDA receptors, SR is predominantly expressed in glutamatergic neurons, and co-release of glutamate and D-serine is required for optimal activation of post-synaptic NMDA receptors.

The NMDA receptor co-agonists, D-serine and glycine, regulate neuronal dendritic architecture in the somatosensory cortex.

There is substantial evidence, both pharmacological and genetic, that hypofunction of the N-methyl-d-aspartate receptor (NMDAR) is a core pathophysiological feature of schizophrenia. There are morphological brain changes associated with schizophrenia, including perturbations in the dendritic morphology of cortical pyramidal neurons and reduction in cortical volume. Our experiments investigated whether these changes in dendritic morphology could be recapitulated in a genetic model of NMDAR hypofunction, the serine racemase knockout (SR-/-) mouse. Pyramidal neurons in primary somatosensory cortex (S1) of SR-/- mice had reductions in the complexity, total length, and spine density of apical and basal dendrites. In accordance with reduced cortical neuropil, SR-/- mice also had reduced cortical volume as compared to wild type mice. Analysis of S1 mRNA by DNA microarray and gene expression analysis revealed gene changes in SR-/- that are associated with psychiatric and neurologic disorders, as well as neurodevelopment. The microarray analysis also identified reduced expression of brain derived neurotrophic factor (BDNF) in SR-/- mice. Follow-up analysis by ELISA confirmed a reduction of BDNF protein levels in the S1 of SR-/- mice. Finally, S1 pyramidal neurons in glycine transporter heterozygote (GlyT1+/-) mutants, which display enhanced NMDAR function, had increased dendritic spine density. These results suggest that proper NMDAR function is important for the arborization and spine density of pyramidal neurons in cortex. Moreover, they suggest that NMDAR hypofunction might, in part, be contributing to the dendritic and synaptic changes observed in schizophrenia and highlight this signaling pathway as a potential target for therapeutic intervention.

Discordant behavioral effects of psychotomimetic drugs in mice with altered NMDA receptor function.

RATIONALE: Enhancement of N-methyl-D: -aspartate receptor (NMDAR) activity through its glycine modulatory site (GMS) is a novel therapeutic approach in schizophrenia. Brain concentrations of endogenous GMS agonist D: -serine and antagonist N-acetyl-aspartylglutamate are regulated by serine racemase (SR) and glutamic acid decarboxylase 2 (GCP2), respectively. Using mice genetically, under-expressing these enzymes may clarify the role of NMDAR-mediated neurotransmission in schizophrenia. OBJECTIVES: We investigated the behavioral effects of two psychotomimetic drugs, the noncompetitive NMDAR antagonist, phencyclidine (PCP; 0, 1.0, 3.0, or 6.0 mg/kg), and the indirect dopamine receptor agonist, amphetamine (AMPH; 0, 1.0, 2.0, or 4.0 mg/kg), in SR -/- and GCP2 -/+ mice. Outcome measures were locomotor activity and prepulse inhibition (PPI) of the acoustic startle reflex. Acute effects of an exogenous GMS antagonist, gavestinel (0, 3.0, or 10.0 mg/kg), on PCP-induced behaviors were examined in wild-type mice for comparison to the mutants with reduced GMS activity. RESULTS: PCP-induced hyperactivity was increased in GCP2 -/+ mice, and PCP-enhanced startle reactivity was increased in SR -/- mice. PCP disruption of PPI was unaffected in either mutant. In contrast, gavestinel attenuated PCP-induced PPI disruption without effect on baseline PPI or locomotor activity. AMPH effects were similar to controls in both mutant strains. CONCLUSIONS: The results of the PCP experiments demonstrate that convergence of pharmacological and genetic manipulations at NMDARs may confound the predictive validity of these preclinical assays for the effects of GMS activation in schizophrenia. The AMPH data provide additional evidence that hyperdopaminergia in schizophrenia may be distinct from NMDAR hypofunction.

Failure of NMDA receptor hypofunction to induce a pathological reduction in PV-positive GABAergic cell markers.

Reduction in cortical presynaptic markers, notably parvalbumin (PV), for the chandelier subtype of inhibitory γ-amino-butyric acid (GABA) interneurons is a highly replicated post-mortem finding in schizophrenia. Evidence from genetic and pharmacological studies implicates hypofunction of N-methyl-d-aspartate receptor (NMDAR)-mediated glutamatergic signaling as a critical component of the pathophysiology of schizophrenia. Serine racemase (SR) produces the endogenous NMDAR co-agonist d-serine, and disruption of the SR gene results in reduced NMDAR signaling. SR null mutant (-/-) mice were used to study the link between NMDAR hypofunction and decreased PV expression, assessed by immunoreactive (IR) cell density in the medial prefrontal cortex and hippocampus and protein levels in brain homogenates from the frontal cortex and hippocampus. Contrary to expectations, SR -/- mice showed modest elevations in PV-IR cell density and no difference in PV expression in brain homogenate. To control for these surprising results, we investigated PV expression in mice and rats following subchronic phencyclidine or ketamine treatments in adulthood. PV expression was not affected by drug these treatment in either species, failing to reproduce previously published findings. Our findings challenge the hypothesis that pathological deficits in PV expression are simply a consequence of NMDAR hypofunction.

Dexmedetomidine use in general anaesthesia.

Dexmedetomidine is a potent and highly selective alpha(2)-adrenoreceptor agonist currently utilized for continuous infusion for sedation/analgesia in the intensive care unit (ICU). Dexmedetomidine offers remarkable pharmacological properties including sedation, anxiolysis, and analgesia with the unique characteristic to cause no respiratory depression. In addition it posses sympatholytic and antinociceptive effects that allow hemodynamic stability during surgical stimulation. Different from most of clinically used anesthetics, dexmedetomidine brings about not only a sedative-hypnotic effect via an action on a single type of receptors, but also an analgesic effect and an autonomic blockade that is beneficial in cardiac risk situations. Several studies have demonstrated its safety, although bradycardia and hypotension are the most predictable and frequent side effects. Dexmedetomidine has shown to consistently reduce opioids, propofol, and benzodiazepines requirements. In the last years it has emerged as an affective therapeutic drug in a wide range of anesthetic management, promising large benefits in the perioperative use. In particular this review focuses on dexmedetomidine utilization in premedication, general surgery, neurosurgery, cardiac surgery, bariatric surgery, and for procedural sedation and awake fiberoptic intubation. In all these fields dexmedetomidine has demonstrated to be an efficacious and safe adjuvant to other sedative and anesthetic medications.

Phenotypic characterization of mice heterozygous for a null mutation of glutamate carboxypeptidase II.

Glutamate is the major excitatory neurotransmitter in the mammalian central nervous system. Disturbed glutamate signaling resulting in hypofunction of N-methyl-D-aspartate receptors (NMDAR) has been implicated in the pathophysiology of schizophrenia. Glutamate Carboxypeptidase II (GCP II) hydrolyzes N-acetyl-alpha L-aspartyl-L-glutamate (NAAG) into glutamate and N-acetyl-aspartate. NAAG is a neuropeptide that is an NMDAR antagonist as well as an agonist for the metabotropic glutamate receptor-3 (mGluR3), which inhibits glutamate release. The aggregate effect of NAAG is thus to attenuate NMDAR activation. To manipulate the expression of GCP II, LoxP sites were inserted flanking exons 1 and 2, which were excised by crossing with a Cre-expressing mouse. The mice heterozygous for this deletion showed a 50% reduction in the expression level of protein and functional activity of GCP II in brain samples. Heterozygous mutant crosses did not yield any homozygous null animals at birth or as embryos (N > 200 live births and fetuses). These data are consistent with the previous report that GCP II homozygous mutant mice generated by removing exons 9 and 10 of GCP II gene were embryonically lethal and confirm our hypothesis that GCP II plays an essential role early in embryonic development. Heterozygous mice, however, developed normally to adulthood and exhibited increased locomotor activity, reduced social interaction, and a subtle cognitive deficit in working memory.

Ube3a mRNA and protein expression are not decreased in Mecp2R168X mutant mice.

Mutations in the transcriptional repressor methyl CpG binding protein 2 (MeCP2) are responsible for most cases of Rett Syndrome (RS), a severe neurodevelopmental disorder characterized by developmental regression, minimal speech, seizures, postnatal microcephaly and hand stereotypies. Absence of the maternal copy of ubiquitin protein ligase 3A (UBE3A) results in Angelman syndrome, also a severe developmental disorder that shares some clinical features with RS. As MeCP2 regulates gene expression, this has led to the hypothesis that MeCP2 may regulate UBE3A expression; however, there are conflicting reports regarding the expression of Ube3a in MeCP2 null mutant mice. We have generated a novel MeCP2 mutant knock-in mouse with the mutation R168X, one of the most common mutations in patients with RS. These mice show features similar to RS, including hypoactivity, forelimb stereotypies, breathing irregularities, weight changes, hind limb atrophy, and scoliosis. The male mice experience early death. Analysis of Ube3a mRNA and protein levels in the Mecp2(R168X) male mice showed no significant difference in expression compared to their wild type littermates.

Learning and memory associated with aggression in Drosophila melanogaster.

Male Drosophila melanogaster (Canton-S strain) exhibit aggression in competition for resources, to defend territory, and for access to mates. In the study reported here, we asked: (i) how long flies fight; (ii) whether flies adopt distinct winning and losing strategies as hierarchical relationships are established; (iii) whether flies exhibit experience-dependent changes in fighting strategies in later fights; and (iv) whether flies fight differently in second fights against familiar or unfamiliar opponents. The results showed that flies fought for up to 5 h. As hierarchical relationships were established, behavioral strategies changed: winners progressively lunged more and retreated less, whereas losers progressively lunged less and retreated more. Encounters between flies were frequent during the first 10 min of pairing and then dropped significantly. To ask whether flies remembered previous fights, they were re-paired with familiar or unfamiliar opponents after 30 min of separation. In familiar pairings, there were fewer encounters during the first 10 min of fighting than in unfamiliar pairings, and former losers fought differently against familiar winners than unfamiliar winners. Former losers lost or no decision was reached in all second fights in pairings with familiar or unfamiliar winners or with naive flies. Winner/winner, loser/loser, and naive/naive pairings revealed that losers used low-intensity strategies in later fights and were unlikely to form new hierarchical relationships, compared with winners or socially naive flies. These results strongly support the idea that learning and memory accompany the changes in social status that result from fruit fly fights.

Changes in heart rate associated with contest outcome in agonistic encounters in lobsters.

Agonistic contests between lobsters housed together in a confined space progress through encounters of increasing intensity until a dominance relationship is established. Once this relationship is established, losing animals continually retreat from the advances of winners. These encounters are likely to consume much energy in both winning and losing animals. Therefore, one might expect involvement of many physiological systems before, during and after fights. Here, we report effects of agonistic encounters on cardiac frequency in winning and losing adult lobsters involved in dyadic interactions. The results show that: (i) small but significant increases in heart rate are observed upon chemical detection of a conspecific; (ii) during agonistic interactions, further increases in heart rate are seen; and (iii) ultimate winners exhibit greater increases in heart rate lasting longer periods of time compared to ultimate losers. Heart rate in winners remains elevated for at least 15 min after the contests have ended and animals have been returned to their home tanks. Reduced effects are seen in second and third pairings between familiar opponents. The sustained changes in heart rate that we observe in winning lobsters may result from hormonal modulation of cardiac function related to the change in social status brought about by contest outcome.