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Summary: Stress adversely affects an array of cognitive functions. Although stress-related disorders are often addressed in adulthood, far less is known about how early-life stress (ELS) affects the developing brain in early postnatal periods. Here we show that ELS, induced by maternal separation, leads to synaptic alteration of layer 2/3 pyramidal neurons in the prefrontal cortex (PFC) of mice. We find that layer 2/3 neurons show increased excitatory synapse numbers following ELS and that this is accompanied by hyperexcitability of PFC-projecting dopamine (DA) neurons in the ventral tegmental area. Notably, excitatory synaptic change requires local signaling through DA D2 receptors. In vivo pharmacological treatment with a D2 receptor agonist in the PFC of control mice mimics the effects of ELS on synaptic alterations. Our findings reveal a neuromodulatory mechanism underlying ELS-induced PFC dysfunction, and this mechanism may facilitate a more comprehensive understanding of how ELS leads to mental disorders.

Summary: Sensory information is encoded within the brain in distributed spatiotemporal patterns of neuronal activity. Understanding how these patterns influence behavior requires a method to measure and to bidirectionally perturb with high spatial resolution the activity of the multiple neuronal cell types engaged in sensory processing. Here, we combined two-photon holography to stimulate neurons expressing blue light-sensitive opsins (ChR2 and GtACR2) with two-photon imaging of the red-shifted indicator jRCaMP1a in the mouse neocortex in vivo. We demonstrate efficient control of neural excitability across cell types and layers with holographic stimulation and improved spatial resolution by opsin somatic targeting. Moreover, we performed simultaneous two-photon imaging of jRCaMP1a and bidirectional two-photon manipulation of cellular activity with negligible effect of the imaging beam on opsin excitation. This all-optical approach represents a powerful tool to causally dissect how activity patterns in specified ensembles of neurons determine brain function and animal behavior. : Forli et al. developed an all-optical method to image and bidirectionally manipulate brain networks with high spatial resolution and minimal crosstalk in the intact mammalian brain. They validate the method across cell types and layers in the mouse neocortex. Keywords: optogenetics, two-photon excitation, digital holography, patterned illumination, two-photon imaging

Irina Piatkov, Dorgival Caetano, Yolinda Assur, Sue Lynn Lau, Trudi Jones, Steven C Boyages, Mark McLean University Clinic and Research Centre Blacktown, Western Sydney University, Western Sydney Local Health District, Blacktown, NSW, Australia Abstract: Clozapine (CZ) has superior efficacy to other antipsychotic agents in the treatment of schizophrenia and has been extensively used in clinical practice. ATP-binding cassette (ABC) transporter proteins are responsible for the distribution of various molecules as well as drugs across extracellular and intracellular membranes, including the blood–brain barrier. Genetic variations in these proteins can account for differences in treatment response. We investigated the influence of ABCB1 rs1045642 and ABCC1 rs212090 single-nucleotide polymorphisms (SNPs) on CZ serum level, clinical outcome, and changes in body mass index (BMI) in the first year of CZ treatment. These polymorphisms influenced baseline BMI in males (p=0.009 and 0.054, B1 and C1, respectively), changes in BMI in males after 3 (p=0.026, ABCB1) and 12 months (p=0.022, ABCC1) of CZ treatment, and level of diastolic pressure (p=0.002 and 0.051, respectively). The combination of ABCB1 + ABCC1 homozygote SNPs was associated with increased CZ and norclozapine serum levels (p=0.054 and 0.010, respectively). ABC transporter SNPs could be potential biomarkers for CZ-induced weight gain and cardiovascular complications. Further pharmacogenetic research is warranted to help clinicians with their treatment decision, including concomitant use of drugs and prevention of side effects. Keywords: ABC transporters, weight gain, blood pressure, rs1045642, rs212090

Sami Shaban, Michelle McLeanDepartment of Medical Education, Faculty of Medicine and Health Sciences, United Arab Emirates University, Al Ain, United Arab EmiratesBackground: The purpose of this study was to examine the predictive potential of multiple indicators (eg, preadmission scores, unit, module and clerkship grades, course and examination scores) on academic performance at medical school, with a view to identifying students at risk.Methods: An analysis was undertaken of medical student grades in a 6-year medical school program at the Faculty of Medicine and Health Sciences, United Arab Emirates University, Al Ain, United Arab Emirates, over the past 14 years.Results: While high school scores were significantly (P < 0.001) correlated with the final integrated examination, predictability was only 6.8%. Scores for the United Arab Emirates university placement assessment (Common Educational Proficiency Assessment) were only slightly more promising as predictors with 14.9% predictability for the final integrated examination. Each unit or module in the first four years was highly correlated with the next unit or module, with 25%–60% predictability. Course examination scores (end of years 2, 4, and 6) were significantly correlated (P < 0.001) with the average scores in that 2-year period (59.3%, 64.8%, and 55.8% predictability, respectively). Final integrated examination scores were significantly correlated (P < 0.001) with National Board of Medical Examiners scores (35% predictability). Multivariate linear regression identified key grades with the greatest predictability of the final integrated examination score at three stages in the program.Conclusion: This study has demonstrated that it may be possible to identify “at-risk” students relatively early in their studies through continuous data archiving and regular analysis. The data analysis techniques used in this study are not unique to this institution.Keywords: at-risk students, grade predictability, scores

This article charts a research project on higher education and poverty reduction chronologically, mapping the process of thinking through and generating an Index of public-good professional education based on literatures; empirical data from actors-lecturers, students, alumni, professional bodies and NGOs; and participatory dialogue. Amartya Sen's capabilities structured the project theoretically, in particular underpinning the original formulation of "professional capabilities" to redefine what counts as being professional. The article further addresses what later emerged as the importance of a broader focus on human development as structuring change and quality in professional education and universities. At the heart of the article's argument is that professional education in South African universities is one area which shapes the relationship between the integrity of professional life and the health of civic cultures, and where an "other-regarding" social consciousness might be fostered through educational arrangements and policy, even in the face of history and social constraints. The Index is presented as an invitation to focus further debate not only in South Africa but globally about higher education, the public good and poverty reduction. (Contains 3 tables, 1 figure, and 2 notes.)

In 2005 New Zealand signalled its intention to reform legal services by contracting research on disabled people's priorities in Auckland. The Legal Services Agency reported that because many disabled people do not have access to necessary legal services in New Zealand their priorities should be identified. This article suggests that the social model offers a philosophical framework for developing services. The relevance of this claim is illustrated from a review of the literature reporting legal issues faced by disabled people in New Zealand. The article concludes with a description of a service proposal based on international models.