Skewed distribution of spines is independent of presynaptic transmitter release and synaptic plasticity, and emerges early during adult neurogenesis.

Dendritic spines are crucial for excitatory synaptic transmission as the size of a spine head correlates with the strength of its synapse. The distribution of spine head sizes follows a lognormal-like distribution with more small spines than large ones. We analysed the impact of synaptic activity and plasticity on the spine size distribution in adult-born hippocampal granule cells from rats with induced homo- and heterosynaptic long-term plasticity in vivo and CA1 pyramidal cells from Munc13-1/Munc13-2 knockout mice with completely blocked synaptic transmission. Neither the induction of extrinsic synaptic plasticity nor the blockage of presynaptic activity degrades the lognormal-like distribution but changes its mean, variance and skewness. The skewed distribution develops early in the life of the neuron. Our findings and their computational modelling support the idea that intrinsic synaptic plasticity is sufficient for the generation, while a combination of intrinsic and extrinsic synaptic plasticity maintains lognormal-like distribution of spines.

Hand hygiene compliance in the intensive care unit: Hand hygiene and glove changes.

BACKGROUND: Hand disinfection (HD) is known to be the single most effective prevention measure to avoid nosocomial infections, but the compliance rate (CR) remains low. The aim of this study was to determine the incidence of HD opportunities and the CR during the treatment of critically ill patients. One special focus was on glove usage to determine whether gloves were substituted for HD. METHODS: This is a single-blinded direct observation of employees of an.ßintensive care unit. One specially educated observer recorded all hand hygiene indications over a period of 21 8-hour shifts as well as performed HD and study of glove use behavior. RESULTS: Over a period of 168.ßhours, 2,036 HDs should be performed during the care for 1 intensive care unit patient. In total, only 690 HDs occurred, resulting in a CR of 33.9%. With regard to the nurses, there was an HD opportunity around the clock every 6.ßminutes on average. About 17% of the total working time would have to be applied for 100% correct hand hygiene application. Donning or changing of gloves took place in 38.2% of all indications for HD. CONCLUSIONS: Our results show that HD opportunities occur in high frequency during the treatment of critically ill patients. The compliance with HD remains too low, even when a 100% CR seems to be unachievable. Improvements should focus on aseptic procedures, combining the lowest CR with the highest procedural risk for the patient. The Healthcare Personal (HCP) uses gloves when an HD opportunity occurs. Implementing glove disinfection strategies in daily routine might help optimize patient care.

Modelling the contributions to hyperexcitability in a mouse model of Alzheimer's disease.

Neuronal hyperexcitability is a pathological characteristic of Alzheimer's disease (AD). Three main mechanisms have been proposed to explain it: (i) dendritic degeneration leading to increased input resistance, (ii) ion channel changes leading to enhanced intrinsic excitability, and (iii) synaptic changes leading to excitation-inhibition (E/I) imbalance. However, the relative contribution of these mechanisms is not fully understood. Therefore, we performed biophysically realistic multi-compartmental modelling of neuronal excitability in reconstructed CA1 pyramidal neurons from wild-type and APP/PS1 mice, a well-established animal model of AD. We show that, for synaptic activation, the excitability-promoting effects of dendritic degeneration are cancelled out by decreased excitation due to synaptic loss. We find an interesting balance between excitability regulation and an enhanced degeneration in the basal dendrites of APP/PS1 cells, potentially leading to increased excitation by the apical but decreased excitation by the basal Schaffer collateral pathway. Furthermore, our simulations reveal three pathomechanistic scenarios that can account for the experimentally observed increase in firing and bursting of CA1 pyramidal neurons in APP/PS1 mice: scenario 1: enhanced E/I ratio; scenario 2: alteration of intrinsic ion channels (IAHP down-regulated; INap , INa and ICaT up-regulated) in addition to enhanced E/I ratio; and scenario 3: increased excitatory burst input. Our work supports the hypothesis that pathological network and ion channel changes are major contributors to neuronal hyperexcitability in AD. Overall, our results are in line with the concept of multi-causality according to which multiple different disruptions are separately sufficient but no single particular disruption is necessary for neuronal hyperexcitability. KEY POINTS: This work presents simulations of synaptically driven responses in pyramidal cells (PCs) with Alzheimer's disease (AD)-related dendritic degeneration. Dendritic degeneration alone alters PC responses to layer-specific input but additional pathomechanistic scenarios are required to explain neuronal hyperexcitability in AD as follows. Possible scenario 1: AD-related increased excitatory input together with decreased inhibitory input (E/I imbalance) can lead to hyperexcitability in PCs. Possible scenario 2: changes in E/I balance combined with altered ion channel properties can account for hyperexcitability in AD. Possible scenario 3: burst hyperactivity of the surrounding network can explain hyperexcitability of PCs during AD.

A general principle of dendritic constancy: A neuron's size- and shape-invariant excitability.

Reducing neuronal size results in less membrane and therefore lower input conductance. Smaller neurons are thus more excitable, as seen in their responses to somatic current injections. However, the impact of a neuron's size and shape on its voltage responses to dendritic synaptic activation is much less understood. Here we use analytical cable theory to predict voltage responses to distributed synaptic inputs in unbranched cables, showing that these are entirely independent of dendritic length. For a given synaptic density, neuronal responses depend only on the average dendritic diameter and intrinsic conductivity. This remains valid for a wide range of morphologies irrespective of their arborization complexity. Spiking models indicate that morphology-invariant numbers of spikes approximate the percentage of active synapses. In contrast to spike rate, spike times do depend on dendrite morphology. In summary, neuronal excitability in response to distributed synaptic inputs is largely unaffected by dendrite length or complexity.