Disruption of Columnar and Laminar Cognitive Processing in Primate Prefrontal Cortex Following Cocaine Exposure

Prefrontal cortical activity in primate brain plays a critical role in cognitive processes involving working memory and the executive control of behavior. Groups of prefrontal cortical neurons within specified cortical layers along cortical minicolumns differentially generate inter- and intra-laminar firing to process relevant information for goal oriented behavior. However, it is not yet understood how cocaine modulates such differential firing in prefrontal cortical layers. Rhesus macaque nonhuman primates (NHPs) were trained in a visual delayed match-to-sample (DMS) task while the activity of prefrontal cortical neurons (areas 46, 8 and 6) was recorded simultaneously with a custom multielectrode array in cell layers 2/3 and 5. Animals were reinforced with juice for correct responses. The first half of the recording session (control) was conducted following saline injection and in the second half of the same session cocaine was administered. Prefrontal neuron activity with respect to inter- and intra-laminar firing in layers 2/3 and 5 was assessed in the DMS task before and after the injection of cocaine. Results showed that firing rates of both pyramidal cells and interneurons increased on Match phase presentation and the Match Response (MR) in both control and cocaine halves of the session. Differential firing under cocaine vs. control in the Match phase was increased for interneurons but decreased for pyramidal cells. In addition, functional\u27 interactions between prefrontal pyramidal cells in layer 2/3 and 5 decreased while intra-laminar cross-correlations in both layers increased. These neural recordings demonstrate that prefrontal neurons differentially encode and process information within and between cortical cell layers via cortical columns which is disrupted in a differential manner by cocaine: administration

Prefrontal cortical microcircuits bind perception to executive control

During the perception-to-action cycle, our cerebral cortex mediates the interactions between the environment and the perceptual-executive systems of the brain. At the top of the executive hierarchy, prefrontal cortical microcircuits are assumed to bind perceptual and executive control information to guide goal-driven behavior. Here, we tested this hypothesis by comparing simultaneously recorded neuron firing in prefrontal cortical layers and the caudate-putamen of rhesus monkeys, trained in a spatial-versus-object, rule-based match-to-sample task. We found that during the perception and executive selection phases, cell firing in the localized prefrontal layers and caudate-putamen region exhibited similar location preferences on spatial-trials, but less on object- trials. Then, we facilitated the perceptual-executive circuit by stimulating the prefrontal infra-granular-layers with patterns previously derived from supra-granular-layers, and produced stimulation-induced spatial preference in percent correct performance on spatial trials, similar to neural tuning. These results show that inter-laminar prefrontal microcircuits play causal roles to the perception-to-action cycle

Distributed Encoding of Spatial and Object Categories in Primate Hippocampal Microcircuits

The primate hippocampus plays critical roles in the encoding, representation, categorization and retrieval of cognitive information. Such cognitive abilities may use the transformational input-output properties of hippocampal laminar microcircuitry to generate spatial representations and to categorize features of objects, images, and their numeric characteristics. Four nonhuman primates were trained in a delayed-match-to-sample (DMS) task while multi-neuron activity was simultaneously recorded from the CA1 and CA3 hippocampal cell fields. The results show differential encoding of spatial location and categorization of images presented as relevant stimuli in the task. Individual hippocampal cells encoded visual stimuli only on specific types of trials in which retention of either, the Sample image, or the spatial position of the Sample image indicated at the beginning of the trial, was required. Consistent with such encoding, it was shown that patterned microstimulation applied during Sample image presentation facilitated selection of either Sample image spatial locations or types of images, during the Match phase of the task. These findings support the existence of specific codes for spatial and numeric object representations in primate hippocampus which can be applied on differentially signaled trials. Moreover, the transformational properties of hippocampal microcircuitry, together with the patterned microstimulation are supporting the practical importance of this approach for cognitive enhancement and rehabilitation, needed for memory neuroprosthetics

Clinical guidelines for the use of lifestyle-based mental health care in major depressive disorder: World Federation of Societies for Biological Psychiatry (WFSBP) and Australasian Society of Lifestyle Medicine (ASLM) taskforce

Objectives: The primary objectives of these international guidelines were to provide a global audience of clinicians with (a) a series of evidence-based recommendations for the provision of lifestyle-based mental health care in clinical practice for adults with Major Depressive Disorder (MDD) and (b) a series of implementation considerations that may be applicable across a range of settings. Methods: Recommendations and associated evidence-based gradings were based on a series of systematic literature searches of published research as well as the clinical expertise of taskforce members. The focus of the guidelines was eight lifestyle domains: physical activity and exercise, smoking cessation, work-directed interventions, mindfulness-based and stress management therapies, diet, sleep, loneliness and social support, and green space interaction. The following electronic bibliographic databases were searched for articles published prior to June 2020: PubMed, EMBASE, The Cochrane Library (Cochrane Database of Systematic Reviews, Cochrane Central Register of Controlled Trials (CENTRAL), Cochrane Methodology Register), CINAHL, PsycINFO. Evidence grading was based on the level of evidence specific to MDD and risk of bias, in accordance with the World Federation of Societies for Biological Psychiatry criteria. Results: Nine recommendations were formed. The recommendations with the highest ratings to improve MDD were the use of physical activity and exercise, relaxation techniques, work-directed interventions, sleep, and mindfulness-based therapies (Grade 2). Interventions related to diet and green space were recommended, but with a lower strength of evidence (Grade 3). Recommendations regarding smoking cessation and loneliness and social support were based on expert opinion. Key implementation considerations included the need for input from allied health professionals and support networks to implement this type of approach, the importance of partnering such recommendations with behaviour change support, and the need to deliver interventions using a biopsychosocial-cultural framework. Conclusions: Lifestyle-based interventions are recommended as a foundational component of mental health care in clinical practice for adults with Major Depressive Disorder, where other evidence-based therapies can be added or used in combination. The findings and recommendations of these guidelines support the need for further research to address existing gaps in efficacy and implementation research, especially for emerging lifestyle-based approaches (e.g. green space, loneliness and social support interventions) where data are limited. Further work is also needed to develop innovative approaches for delivery and models of care, and to support the training of health professionals regarding lifestyle-based mental health care

The Grizzly, November 1, 1985

Exploring Faculty/Student Research Opportunities • Dean Muench: An Expert on RA Supervision • Letters: No More Roving Reporter Complaints, Please; J. Board Decision Not Seen as Fair; Campus Social Life Taking a Left Turn • Editorial: Discontent is in the Air • In Search of Success: Vanessa Embarks on her Career • Liberal Arts and Science to be Discussed on Founder\u27s Day • Loss to Penn State Works Against the Bears • Grizzlies Prepare for Make or Break Game vs. Mules • Harriers Race Into Autumn • Philadelphia Sports: Frustrating Times • Soccer Team Ties a Few • Athlete of the Week: Steve Coulter • College Campaign Launched • Tuition: An Ever-Increasing Problem • Exercise to Release Stress • Medical Schools Suffering • Ursinus Aid to Mexico • Alcohol and Advertising • Open Dialog Interaction: Jerry Falwell in Politics; Protecting America • Natural Science Perspectives • New Course Offerings: Argument and Debate; East Asian Literature and Politics • Reimert Task Force Means Law and Order, of Coursehttps://digitalcommons.ursinus.edu/grizzlynews/1150/thumbnail.jp

Progress in thermochemical hydrogen production with the copper–chlorine cycle

Recent advances are reported by an international team on research and development of the copper chlorine (Cu–Cl) cycle for thermochemical hydrogen production. New experimental and numerical results are given for several processes of the cycle. Experimental results for CuCl/HCl electrolysis and integration of unit operations in the Cu–Cl cycle are presented. A new solubility model for the CuCl–CuCl2–HCl–H2O quaternary system is presented, which optimizes the cupric chloride selective precipitation prior to the hydrolysis reactor. Also, recent progress on photo-electrochemical cell development for enhancement of the electrolysis process is reported along with its integration with a concentrated solar radiation system

The RING-CH ligase K5 antagonizes restriction of KSHV and HIV-1 particle release by mediating ubiquitin-dependent endosomal degradation of tetherin

Tetherin (CD317/BST2) is an interferon-induced membrane protein that inhibits the release of diverse enveloped viral particles. Several mammalian viruses have evolved countermeasures that inactivate tetherin, with the prototype being the HIV-1 Vpu protein. Here we show that the human herpesvirus Kaposi's sarcoma-associated herpesvirus (KSHV) is sensitive to tetherin restriction and its activity is counteracted by the KSHV encoded RING-CH E3 ubiquitin ligase K5. Tetherin expression in KSHV-infected cells inhibits viral particle release, as does depletion of K5 protein using RNA interference. K5 induces a species-specific downregulation of human tetherin from the cell surface followed by its endosomal degradation. We show that K5 targets a single lysine (K18) in the cytoplasmic tail of tetherin for ubiquitination, leading to relocalization of tetherin to CD63-positive endosomal compartments. Tetherin degradation is dependent on ESCRT-mediated endosomal sorting, but does not require a tyrosine-based sorting signal in the tetherin cytoplasmic tail. Importantly, we also show that the ability of K5 to substitute for Vpu in HIV-1 release is entirely dependent on K18 and the RING-CH domain of K5. By contrast, while Vpu induces ubiquitination of tetherin cytoplasmic tail lysine residues, mutation of these positions has no effect on its antagonism of tetherin function, and residual tetherin is associated with the trans-Golgi network (TGN) in Vpu-expressing cells. Taken together our results demonstrate that K5 is a mechanistically distinct viral countermeasure to tetherin-mediated restriction, and that herpesvirus particle release is sensitive to this mode of antiviral inhibition

Electrophysiology of Inhibitory Control in the Context of Emotion Processing in Children With Autism Spectrum Disorder

Autism Spectrum Disorder (ASD) is an increasingly common developmental disorder that affects 1 in 59 children. Despite this high prevalence of ASD, knowledge regarding the biological basis of its associated cognitive difficulties remains scant. In this study, we aimed to identify altered neurophysiological responses underlying inhibitory control and emotion processing difficulties in ASD, together with their associations with age and various domains of cognitive and social function. This was accomplished by assessing electroencephalographic recordings during an emotional go/nogo task alongside parent rating scales of behavior. Event related potential (ERP) N200 component amplitudes were reduced in children with ASD compared to typically developing (TD) children. No group differences were found, however, for task performance, P300 amplitude or latency, or N170 amplitude or latency, suggesting that individuals with ASD may only present conflict monitoring abnormalities, as reflected by the reduced N200 component, compared to TD individuals. Consistent with previous findings, increased age correlated with improved task performance scores and reduced N200 amplitude in the TD group, indicating that as these children develop, their neural systems become more efficient. These associations were not identified in the ASD group. Results also showed significant associations between increased N200 amplitudes and improved executive control abilities and decreased autism traits in TD children only. The newly discovered findings of decreased brain activation in children with ASD, alongside differences in correlations with age compared to TD children, provide a potential neurophysiological indicator of atypical development of inhibitory control mechanisms in these individuals