Genetic feedback regulation of frontal cortical neuronal ensembles through activity-dependent Arc expression and dopaminergic input

Mental functions involve coordinated activities of specific neuronal ensembles that are embedded in complex brain circuits. Aberrant neuronal ensemble dynamics is thought to form the neurobiological basis of mental disorders. A major challenge in mental health research is to identify these cellular ensembles and determine what molecular mechanisms constrain their emergence and consolidation during development and learning. Here, we provide a perspective based on recent studies that use activity-dependent gene Arc/Arg3.1 as a cellular marker to identify neuronal ensembles and a molecular probe to modulate circuit functions. These studies have demonstrated that the transcription of Arc is activated in selective groups of frontal cortical neurons in response to specific behavioral tasks. Arc expression regulates the persistent firing of individual neurons and predicts the consolidation of neuronal ensembles during repeated learning. Therefore, the Arc pathway represents a prototypical example of activity-dependent genetic feedback regulation of neuronal ensembles. The activation of this pathway in the frontal cortex starts during early postnatal development and requires dopaminergic input. Conversely, genetic disruption of Arc leads to a hypoactive mesofrontal dopamine circuit and its related cognitive deficit. This mutual interaction suggests an auto-regulatory mechanism to amplify the impact of neuromodulators and activity-regulated genes during postnatal development. Such a mechanism may contribute to the association of mutations in dopamine and Arc pathways with neurodevelopmental psychiatric disorders. As the mesofrontal dopamine circuit shows extensive activity-dependent developmental plasticity, activity-guided modulation of dopaminergic projections or Arc ensembles during development may help to repair circuit deficits related to neuropsychiatric disorders

Performance evaluation and sustainability challenges of tropically adopted exotic chicken breeds in Northwest Ethiopia

AbstractThe study aimed to describe performance and challenges of village-based exotic chicken production in Northwest Ethiopia. Three zones, 13 districts, and 300 households were selected. The data were collected via semi-structured questionnaires, field observations, and key informant interviews. In the study area, the average exotic chicken holding per household was 4.27 ± 0.13 birds. The most dominant flocks were hens followed by pullets with high significant difference (P < 0.01) in the midland agro ecology. The annual number of egg production of Sasso, Bovans brown, and Koekoek was 110.99 ± 1.45, 123.29 ± 1.16, and 102.92 ± 1.22, respectively. The average age of pullets at first egg laying was 5.25 ± 0.03 (Sasso), 5.53 ± 0.02 (Bovans brown), and 5.71 ± 0.03 (Koekoek) months. The age of cockerels (mean ± SE) at first mating was 4.18 ± 0.06 (Sasso), 4.89 ± 0.06 (Bovans brown), and 5.15 ± 0.06 (Koekoek) months. Male age (mean ± SE) at slaughter of Sasso, Bovans brown, and Koekoek were 4.24 ± 0.06, 6.28 ± 0.05, and 5.68 ± 0.06 months, respectively. The lack of improved breed supply was the first production challenge followed by feed shortages and disease outbreaks. Therefore, designing exotic chicken market supply, practicing ration formulation with locally available feed resources, controlling disease, and predator with biosecurity measures and other proper management strategies in respective of agro ecologies could be mandatory

Conservation and novelty in the evolution of cell adhesion and extracellular matrix genes

New proteins and modules have been invented throughout evolution. Gene birth dates in Caenorhabditis elegans range from the origins of cellular life through adaptation to a soil habitat. Possibly half are metazoan genes, having arisen sometime between the yeast-metazoan and nematode-chordate separations. These include basement membrane and cell adhesion molecules implicated in tissue organization. By contrast, epithelial surfaces facing the environment have specialized components invented within the nematode lineage. Moreover, interstitial matrices were likely elaborated within the vertebrate lineage. A strategy for concerted evolution of new gene families, as well as conservation of adaptive genes, may underlie the differences between heterochromatin and euchromatin

Genetic Disruption of Arc/Arg3.1 in Mice Causes Alterations in Dopamine and Neurobehavioral Phenotypes Related to Schizophrenia

Human genetic studies have recently suggested that the postsynaptic activity-regulated cytoskeleton-associated protein (Arc) complex is a convergence signal for several genes implicated in schizophrenia. However, the functional significance of Arc in schizophrenia-related neurobehavioral phenotypes and brain circuits is unclear. Here, we find that, consistent with schizophrenia-related phenotypes, disruption of Arc in mice produces deficits in sensorimotor gating, cognitive functions, social behaviors, and amphetamine-induced psychomotor responses. Furthermore, genetic disruption of Arc leads to concomitant hypoactive mesocortical and hyperactive mesostriatal dopamine pathways. Application of a D1 agonist to the prefrontal cortex or a D2 antagonist in the ventral striatum rescues Arc-dependent cognitive or psychomotor abnormalities, respectively. Our findings demonstrate a role for Arc in the regulation of dopaminergic neurotransmission and related behaviors. The results also provide initial biological support implicating Arc in dopaminergic and behavioral abnormalities related to schizophrenia

Conservation and novelty in the evolution of cell adhesion and extracellular matrix genes

New proteins and modules have been invented throughout evolution. Gene birth dates in Caenorhabditis elegans range from the origins of cellular life through adaptation to a soil habitat. Possibly half are metazoan genes, having arisen sometime between the yeast-metazoan and nematode-chordate separations. These include basement membrane and cell adhesion molecules implicated in tissue organization. By contrast, epithelial surfaces facing the environment have specialized components invented within the nematode lineage. Moreover, interstitial matrices were likely elaborated within the vertebrate lineage. A strategy for concerted evolution of new gene families, as well as conservation of adaptive genes, may underlie the differences between heterochromatin and euchromatin

Health-related quality of life in left ventricular assist device-supported patients

Aims This study aimed to evaluate the different health-related quality of life (HR-QoL) aspects in patients with both short-term and long-term duration LVAD support at pre-specified time intervals. Methods and results We performed a single-centre HR-QoL analysis of short-term and long-term LVAD-supported patients using the short version of the Kansas City Cardiomyopathy Questionnaire (KCCQ-12) and the Changes in Sexual Functioning Questionnaire along with a survey to evaluate patients social and driving routines. Data were collected at baseline and at 6 or 12 month follow-up. Included were 46 patients with a median time from LVAD implantation of 1.1 [inter-quartile range (IQR) 0.5, 2.6] years. The median KCCQ-12 summary score was 56 (IQR 29, 74) with most favourable scores in the symptom frequency domain [75 (IQR 50, 92)] and worse scores in the physical limitation [42 (IQR 25, 75)] and QoL [44 (IQR 25, 75)] domains. No significant changes were apparent during study follow-up [KCCQ-12 summary score 56 (IQR 35, 80)], and no significant correlation between the KCCQ-12 summary score and ventricular assist device-support duration was detected (r = -0.036, P = 0.812). Sexual dysfunction was noted across all domains with a cumulative score of 31 (IQR 22, 42). Seventy-six per cent of patients resumed driving after LVAD implantation, and 43% of patients reported they socialize with family and friends more frequently since surgery. Conclusions Short-term and long-term LVAD-supported patients had impaired HR-QoL and sexual function at baseline and at follow-up yet reported an improvement in social interactions and independency. A broader spectrum of patients reported HR-QoL measures should be integrated into the pre-LVAD implantation assessment and preparation

Health‐related quality of life in left ventricular assist device‐supported patients

Aims This study aimed to evaluate the different health-related quality of life (HR-QoL) aspects in patients with both short-term and long-term duration LVAD support at pre-specified time intervals. Methods and results We performed a single-centre HR-QoL analysis of short-term and long-term LVAD-supported patients using the short version of the Kansas City Cardiomyopathy Questionnaire (KCCQ-12) and the Changes in Sexual Functioning Questionnaire along with a survey to evaluate patients social and driving routines. Data were collected at baseline and at 6 or 12 month follow-up. Included were 46 patients with a median time from LVAD implantation of 1.1 [inter-quartile range (IQR) 0.5, 2.6] years. The median KCCQ-12 summary score was 56 (IQR 29, 74) with most favourable scores in the symptom frequency domain [75 (IQR 50, 92)] and worse scores in the physical limitation [42 (IQR 25, 75)] and QoL [44 (IQR 25, 75)] domains. No significant changes were apparent during study follow-up [KCCQ-12 summary score 56 (IQR 35, 80)], and no significant correlation between the KCCQ-12 summary score and ventricular assist device-support duration was detected (r = -0.036, P = 0.812). Sexual dysfunction was noted across all domains with a cumulative score of 31 (IQR 22, 42). Seventy-six per cent of patients resumed driving after LVAD implantation, and 43% of patients reported they socialize with family and friends more frequently since surgery. Conclusions Short-term and long-term LVAD-supported patients had impaired HR-QoL and sexual function at baseline and at follow-up yet reported an improvement in social interactions and independency. A broader spectrum of patients reported HR-QoL measures should be integrated into the pre-LVAD implantation assessment and preparation