A quantitative understanding of the dynamics of biological neural networks is fundamental to gaining insight into information processing in the brain. While techniques exist to measure spatial or temporal properties of these networks, it remains a significant challenge to resolve the neural dynamics with subcellular spatial resolution. In this work we consider a fundamentally new form of wide-field imaging for neuronal networks based on the nanoscale magnetic field sensing properties of optically active spins in a diamond substrate. We analyse the sensitivity of the system to the magnetic field generated by an axon transmembrane potential and confirm these predictions experimentally using electronically-generated neuron signals. By numerical simulation of the time dependent transmembrane potential of a morphologically reconstructed hippocampal CA1 pyramidal neuron, we show that the imaging system is capable of imaging planar neuron activity non-invasively at millisecond temporal resolution and micron spatial resolution over wide-fields.

Many idiopathic epilepsy syndromes have a characteristic age dependence, the underlying molecular mechanisms of which are largely unknown. Here we propose a mechanism that can explain that epileptic spells in benign familial neonatal-infantile seizures occur almost exclusively during the first days to months of life. Benign familial neonatal-infantile seizures are caused by mutations in the gene SCN2A encoding the voltage-gated Na⁺ channel Na_V1.2. We identified two novel SCN2A mutations causing benign familial neonatal-infantile seizures and analysed the functional consequences of these mutations in a neonatal and an adult splice variant of the human Na⁺ channel Na_V1.2 expressed heterologously in tsA201 cells together with beta1 and beta2 subunits. We found significant gating changes leading to a gain-of-function, such as an increased persistent Na⁺ current, accelerated recovery from fast inactivation or altered voltage-dependence of steady-state activation. Those were restricted to the neonatal splice variant for one mutation, but more pronounced for the adult form for the other, suggesting that a differential developmental splicing does not provide a general explanation for seizure remission. We therefore analysed the developmental expression of Na_V1.2 and of another voltage-gated Na⁺ channel, Na_V1.6, using immunohistochemistry and real-time reverse transcription–polymerase chain reaction in mouse brain slices. We found that Na_V1.2 channels are expressed early in development at axon initial segments of principal neurons in the hippocampus and cortex, but their expression is diminished and they are gradually replaced as the dominant channel type by Na_V1.6 during maturation. This finding provides a plausible explanation for the transient expression of seizures that occur due to a gain-of-function of mutant Na_V1.2 channels.

Small intestinal movements depend on the composition of the chyme with mixing predominating at high nutrient levels and propulsion being prevalent at low nutrient levels. The mechanisms coupling nutrients to motility are unknown. We used computer analysis of video recordings of isolated guinea‐pig duodenum, jejunum and ileum to examine movements induced by a fatty acid, decanoic acid. Increasing intraluminal pressure past a threshold using control saline consistently evoked propulsive reflexes: lumen‐occluding constrictions appeared at the oral end propagating at 20.4 ± 2.4 mm s⁻¹ (mean ±s.d., jejunum) to the anal end before being repeated until the intraluminal pressure was returned to control. Subthreshold pressure increases sometimes evoked a transient series of constrictions appearing at the oral end and propagating anally at 18.4 ± 4.7 mm s⁻¹ (jejunum). At basal pressures, decanoic acid dose‐dependently induced motor activity consisting of 40–60 s episodes of constrictions separated by 40–200 s periods of quiescence and lasting up to 2 h. Five contraction patterns were identified within episodes including localized stationary constrictions; constrictions that propagated slowly (5–8 mm s⁻¹) for short distances orally or anally; and constrictions that propagated orally or anally for the length of the preparation at 14–20 mm s⁻¹. Decanoic acid induced motor activity was reversibly abolished by tetrodotoxin (3 μm), hyoscine (1 μm) and hexamethonium (100 μm), but was insensitive to blockade of P2 purinoceptors by PPADS (60 μm). Thus, decanoic acid induces motor activity equivalent to segmentation in guinea‐pig small intestine in vitro and this depends on intrinsic neural pathways.

The genetic architecture of common epilepsies is largely unknown. HCNs are excellent epilepsy candidate genes because of their fundamental neurophysiological roles. Screening in subjects with febrile seizures and genetic epilepsy with febrile seizures plus revealed that 2.4% carried a common triple proline deletion (delPPP) in HCN2 that was seen in only 0.2% of blood bank controls. Currents generated by mutant HCN2 channels were ∼35% larger than those of controls; an effect revealed using automated electrophysiology and an appropriately powered sample size. This is the first association of HCN2 and familial epilepsy, demonstrating gain of function of HCN2 current as a potential contributor to polygenic epilepsy. ANN NEUROL 2010;67:542–546