The Impact of Perineuronal Net Digestion Using Chondroitinase ABC on the Intrinsic Physiology of Cortical Neurons.

Perineuronal nets (PNNs) are a form of aggregate Extracellular Matrix (ECM) in the brain. Recent evidence suggests that the postnatal deposition of PNNs may play an active role in regulating neuroplasticity and, potentially, neurological disorders. Observations of high levels of PNN expression around somas, proximal dendrites, and axon initial segments of a subtype of neurons have also led to proposals that PNNs may modulate the intrinsic properties of the neurons they ensheathe. While high levels of PNNs are postnatally expressed throughout the neocortex, it is still unclear how they impact the neuronal physiology of the many classes and subtypes of neurons that exist. In this study, we demonstrate that Chondroitinase ABC digestion of PNNs from acute cortical slices from juvenile mice (P28-35) resulted in neuron-specific impacts on intrinsic physiology. Fast spiking (FS) interneurons showed decreased input resistance, resting membrane potential (RMP), reduced action potential (AP) peaks and altered spontaneous synaptic inputs. Low-Threshold Spiking interneurons showed altered rebound depolarizations and decreased frequency of spontaneous synaptic inputs. Putative excitatory neurons; regular spiking, bursting, and doublet phenotypes did not demonstrate any alterations. Our data indicate that chABC-sensitive PNNs may specifically regulate the intrinsic and synaptic physiology of inhibitory interneurons.

Diplomatic and operational adaptations to global health programmes in post-conflict settings: contributions of monitoring and evaluation systems to health sector development and 'nation-building' in South Sudan.

Monitoring and evaluation (M&E) systems are an essential element of functioning and accountable global health programmes. In post-conflict settings, the role of M&E systems is also critical to ensure that health services are being delivered to those populations and regions most in need. Given the inherent challenges of health service delivery in such environments, a range of both diplomatic and operational adaptations to M&E procedures are necessary. Using the '12 components' of a functioning M&E system as a conceptual and analytical framework, we observed and reviewed the key challenges to M&E systems in South Sudan as part of a broader review of United Nations Development Programme (UNDP) activities supported by the Global Fund to Fight AIDS, Tuberculosis and Malaria. Based on additional interview-based reviews and analyses of M&E activities, a list of adaptations to standardized M&E procedures in response to post-conflict environmental challenges was developed. The study concludes that development and implementation of M&E systems in post-conflict environments requires extensive adaptations to conventional procedures. Flexible and adaptable as well as 'diplomatically sensitized' M&E systems are considered to be essential to the successful completion of M&E-related activities, and may also contribute to broader international relations, 'nation-building', and peace-keeping goals.