TrkB Activation during a Critical Period Mimics the Protective Effects of Early Visual Experience on Perception and the Stability of Receptive Fields in Adult Superior Colliculus.

During a critical period in development, spontaneous and evoked retinal activity shape visual pathways in an adaptive fashion. Interestingly, spontaneous activity is sufficient for spatial refinement of visual receptive fields (RFs) in superior colliculus (SC) and visual cortex (V1), but early visual experience is necessary to maintain inhibitory synapses and stabilize RFs in adulthood (Carrasco et al., 2005, 2011; Carrasco and Pallas, 2006; Balmer and Pallas, 2015a). In V1, BDNF and its high-affinity receptor TrkB are important for development of visual acuity, inhibition, and regulation of the critical period for ocular dominance plasticity (Hanover et al., 1999; Huang et al., 1999; Gianfranceschi et al., 2003). To examine the generality of this signaling pathway for visual system plasticity, the present study examined the role of TrkB signaling during the critical period for RF refinement in SC. Activating TrkB receptors during the critical period (P33-P40) in dark reared subjects produced normally refined RFs, and blocking TrkB receptors in light-exposed animals resulted in enlarged adult RFs like those in dark reared animals. We also report here that deprivation- or TrkB blockade-induced RF enlargement in adulthood impaired fear responses to looming overhead stimuli and negatively impacted visual acuity. Thus, early TrkB activation is both necessary and sufficient to maintain visual RF refinement, robust looming responses, and visual acuity in adulthood. These findings suggest a common signaling pathway exists for the maturation of inhibition between V1 and SC.SIGNIFICANCE STATEMENT Receptive field refinement in superior colliculus differs from more commonly studied examples of critical period plasticity in visual pathways in that it does not require visual experience to occur; rather, spontaneous activity is sufficient. Maintenance of refinement beyond puberty requires a brief, early exposure to light to stabilize the lateral inhibition that shapes receptive fields. We find that TrkB activation during a critical period can substitute for visual experience in maintaining receptive field refinement into adulthood, and that this maintenance is beneficial to visual survival behaviors. Thus, as in some other types of plasticity, TrkB signaling plays a crucial role in receptive field refinement.

The impact of enriched environment and transplantation of murine cortical embryonic stem cells on recovery from controlled cortical contusion injury.

PURPOSE: The effectiveness of embryonic stem cell (eSC) therapy has been explored in many models of neurological disease and several research groups have shown that eSC treatment leads to improved outcomes in pre-clinical models of traumatic brain injury (TBI). Though functional recovery occurs, few surviving eSCs appear to develop neuronal characteristics; instead the majority of the surviving eSC express glial phenotypes. Additionally, researchers have shown that enriching the post-surgical environment of the subject promotes functional recovery following TBI. The purpose of the current project was to determine if post-surgical environmental enrichment (EE) impacts the survival, migration, and integration of eSCs in a rodent model of TBI and if the presence of these cells lead to improved outcomes. METHODS: In the current study, the medial frontal cortex (MFC) of rats was injured using a controlled cortical impact (CCI) device. Immediately following injury the rats were placed into either EE or standard environment (SE) housing and then seven days post-injury rats received either murine cortical eSC or media. Behavioral testing consisted of the Morris water maze (MWM), Barnes Maze (BM), and Rotarod tasks (RR). RESULTS: On the MWM task, TBI/eSC/EE animals performed as well as the Sham/SE and Sham/EE groups. The TBI/eSC/SE, TBI/Media/EE, and TBI/Media/SE groups were impaired compared to the controls. By the end of training on the BM there were no differences between the Sham, TBI/Media/EE, and TBI/eSC/EE groups. On the RR task all animals placed in the EE performed equally well and significantly better than their SE housed counterparts. By the end of training on the RR task, the TBI/eSC/EE group performed as well as the sham counterparts, and though not significant they also surpassed the performance of the injured animals that received enrichment or eSC treatment alone. CONCLUSIONS: Combing therapeutic strategies with enriching the post-injury environment is likely to be an important addition to determining the efficacy of pre-clinical therapies.

Successive bilateral frontal controlled cortical impact injuries show behavioral savings.

Traumatic brain injuries (TBIs) affect millions of people each year. Research investigating repeated or serial damage in the form of lesions indicates that behavioral deficits are reduced in animals given sequential lesions separated by a sufficient period of recovery. In the lesion literature, this phenomenon is known as the serial lesion effect (SLE). Although the SLE phenomenon is established in the lesion literature, it has not been thoroughly investigated under current models of brain injury. In the current study, a controlled cortical impact of the bilateral frontal cortex was performed in either a single procedure or a serial procedure separated by two weeks. Rats were tested on the Morris water maze, bilateral tactile adhesive removal task, rotarod and Barnes maze task to determine behavioral deficits. Histology was performed to determine lesion size and astrocyte and microglial response. A serial lesion effect was demonstrated across a majority of the behavioral tasks. However, histological analyses did not suggest a clear mechanistic link to the behavioral phenomena. This is the first study to demonstrate the SLE in a model of TBI, suggesting that behavioral deficits may actually be reduced in repeated head injuries, given an adequate time window between injuries.

Clinical and economic outcomes from the UK pilot psychiatric services for personality-disordered offenders.

Personality-disordered offenders are difficult individuals to manage, and knowledge about effective treatment is sparse. In the UK, novel forensic psychiatric services were recently established for the treatment of offenders with personality disorder. In this paper we report the clinical and economic findings from a 2-year follow-up of a cohort of service users recruited from these services. Baseline information on developmental, clinical and offending histories was obtained from case records. Case records were checked at 6 and 24 months for new episodes of self-harm, violence, alcohol and substance use, and offending behaviour. Ratings of social functioning and therapeutic alliance were obtained from service users at baseline, 6 and 24 months. Fifty-six percent of service users were still engaged with the services at 24-month follow-up. Service users involved in the greatest number of behavioural incidents had greater impairment in baseline social functioning and lower IQ scores. There was no significant change in either therapeutic alliance or social functioning at 6 or 24 months. The economic analysis showed that although the services were predominantly run by the Health Service, there were considerable economic burdens shared by other service providers. Treatment costs at six-month follow-up were also significantly higher. Implications are discussed.

An evaluation of new services for personality-disordered offenders: staff and service user perspectives.

BACKGROUND: Little is known about effective treatment for personality-disordered (PD) offenders. We aimed to obtain the perspective of service users and staff on: (a) the experience of receiving treatment; and (b) the experience of delivering treatment, within new forensic services for PD offenders. MATERIAL: Thematic analysis was applied to qualitative interviews with 30 service users and 22 staff. DISCUSSION: Service users perceived that they were making positive changes in the areas of anger management, communication, self-harm, self-esteem and insight into their difficulties. Undertaking the clinical work was extremely stressful for staff. CONCLUSIONS: Forensic PD services may be having an important impact on the quality of service users' lives. Whether treatment is successful in reducing long-term risk to others remains to be seen, and the cost-effectiveness of these services needs to be examined.

Electrostatic deposition of graphene in a gaseous environment: a deterministic route for synthesizing rolled graphenes?

The synthesis of single-wall carbon nanotubes of desired diameters and chiralities is critical to the design of nanoscale electronic devices with desired properties. The existing methods are based on self-assembly, therefore lacking control over the diameters and chiralities. The present work reports a direct route for rolling graphene. Specifically, we found that the electrostatic deposition of graphene yielded: (i) flat graphene layers under high vacuum (10(-7) Torr), (ii) completely scrolled graphene under hydrogen atmosphere, (iii) partially scrolled graphene under nitrogen atmosphere, and (iv) no scrolling for helium atmospheres. Our study shows that the application of the electrostatic field facilitates the rolling of graphene sheets exposed to appropriate gases and allows the rolling of any size of graphene. The technique proposed here, in conjunction with a technique that produces graphene nanoribbons of uniform widths, will have significant impact on the development of carbon nanotube based devices. Furthermore, the present technique may be applied to obtain tubes/scrolls of other layered materials.

Best practice using Excellence in Practice Accreditation Scheme.

This article describes how the University of Teesside School of Health and Social Care practice development team, in partnership with local professional colleagues and organizations, have addressed the issue of providing continuous quality evidence-based practice within the context of clinical governance. The newly devised Excellence in Practice Accreditation Scheme (EPAS) measures the standard of practice for a given health and social care setting by providing objective data indicating the level of clinical excellence obtained for the team or organization. The EPAS differs from other organizational accreditation schemes by facilitating excellence based upon a comprehensive set of measurable core standards: working in organizations, collaborative working, user-focused care, continuous quality improvements, performance management, and measuring efficiency and effectiveness. The standards are derived from a professional peer review of best practices. The uniqueness of EPAS is in consolidating the various organizational standards to elicit the core themes related to best practice where individuals, teams and organizations can be benchmarked and accredited for a level of excellence.