K-ATP channels in dopamine substantia nigra neurons control bursting and novelty-induced exploration.

Phasic activation of the dopamine (DA) midbrain system in response to unexpected reward or novelty is critical for adaptive behavioral strategies. This activation of DA midbrain neurons occurs via a synaptically triggered switch from low-frequency background spiking to transient high-frequency burst firing. We found that, in medial DA neurons of the substantia nigra (SN), activity of ATP-sensitive potassium (K-ATP) channels enabled NMDA-mediated bursting in vitro as well as spontaneous in vivo burst firing in anesthetized mice. Cell-selective silencing of K-ATP channel activity in medial SN DA neurons revealed that their K-ATP channel-gated burst firing was crucial for novelty-dependent exploratory behavior. We also detected a transcriptional upregulation of K-ATP channel and NMDA receptor subunits, as well as high in vivo burst firing, in surviving SN DA neurons from Parkinson's disease patients, suggesting that burst-gating K-ATP channel function in DA neurons affects phenotypes in both disease and health.

Measuring burstiness and regularity in oscillatory spike trains.

The ability of neurons to emit different firing patterns such as bursts or oscillations is important for information processing in the brain. In dopaminergic neurons, prominent patterns include repetitive, oscillatory bursts, regular pacemakers, and irregular spike trains with nonstationary properties. In order to describe and measure the variability of these patterns, we describe burstiness and regularity in a single model framework. We present a doubly stochastic spike train model in which a background oscillation with independent and normally distributed intervals gives rise to either single spikes or bursty spike events with Gaussian firing intensities. Five easily interpretable parameters allow a classification into bursty or single spike and irregularly or regularly oscillating firing patterns. This classification is based primarily on features of the autocorrelation histogram which are usually studied qualitatively by visual inspection. The present model provides a quantitative and objective classification scheme and relates these features directly to the underlying processes. In addition, confidence intervals visualize the uncertainty of parameter estimation and classification precision. We apply the model to a data set obtained from single dopaminergic substantia nigra neurons recorded extracellularly in vivo. The model is able to represent a high variety of discharge patterns observed empirically, and the classification agrees closely with visual inspection. In addition, changes in the parameters can be studied quantitatively, including also the properties related to bursting behavior. Thus, the proposed model can be used for the description of neuronal firing patterns and the investigation of their dynamical changes with cellular and experimental conditions.

A new concept for the cephalometric evaluation of craniofacial patterns (multiharmony).

Orthodontists commonly specify the alignment of the teeth and jaws by means of a set of k angles and their relationship with each other. Each individual can thus be visualized as a point in k-dimensional space. Individuals regarded as having an ideal occlusion and well-balanced face, form a cloud of points that is termed the 'norm' population. Individuals far from the cloud require orthodontic intervention. In this study, a method is presented--the multiharmony method (MHM), which assists in treatment planning. With multiple regression analysis, the expected value that each angle should take in a norm individual when the remaining angles are given is estimated. The residual difference between the measured angle and its expected value then indicates the deviation from a harmonic appearance in the respective angle. The MHM was applied to a data set of 134 Korean individuals identified as the norm population (Class I, mean age: 19.6 years) and to 87 patients (Class III, mean age: 21.2 years). From the number and size of the residuals, the two populations could be separated almost completely. Almost all patients showed residuals larger than any residual in the norm population (sensitivity: 99 per cent), whereas 90 per cent of all norm individuals showed no extreme residuals. The MHM can also be used to assist in visualizing different treatment effects, thereby assisting the orthodontist in choosing the best course of treatment for each patient.