SummaryDirect electrical access to presynaptic ion channels has hitherto been limited to large specialized terminals such as the calyx of Held or hippocampal mossy fiber bouton. The electrophysiology and ion-channel complement of far more abundant small synaptic terminals (≤1 μm) remain poorly understood. Here we report a method based on superresolution scanning ion conductance imaging of small synapses in culture at approximately 100–150 nm 3D resolution, which allows presynaptic patch-clamp recordings in all four configurations (cell-attached, inside-out, outside-out, and whole-cell). Using this technique, we report presynaptic recordings of K+, Na+, Cl−, and Ca2+ channels. This semiautomated approach allows direct investigation of the distribution and properties of presynaptic ion channels at small central synapses.Video Abstract

BackgroundThe aetiology of apparently sporadic amyotrophic lateral sclerosis (ALS) is unknown, but prenatal factors are known to influence disease development. In both men and women, motor neurons require testosterone for survival and axonal regeneration after injury, and androgen insensitivity leads to a form of motor neuron degeneration in men. Reduction in the ratio of index to ring finger length (2D:4D ratio) is considered a surrogate marker for high prenatal testosterone levels in both men and women. The authors therefore tested the hypothesis that prenatal testosterone irrespective of gender is an independent risk factor for the development of ALS later in life, and that this would be reflected in a lower 2D:4D ratio in both men and women with ALS. Methods Patients and unrelated control individuals attending a specialist tertiary referral centre for ALS were studied. A digital camera was used to photograph hands. Finger lengths were measured by four independent scorers blind to caseecontrol status, and the mean 2D:4D ratio derived. Analysis was by linear regression and receiver-operator-curve analysis. Results Controlling for differences in sex ratio between groups, the 2D:4D ratio was lower for people with ALS (n¼47) than for controls (n¼63) (r¼À0.25, two-tailed p¼0.009). Conclusions Patients with ALS have a lower 2D:4D ratio, consistent with higher prenatal circulating levels of testosterone, and possibly a prenatal influence of testosterone on motor-neuron vulnerability in later life.

Hippocampal theta oscillations have been implicated in spatial memory function in both rodents and humans. What is less clear is how hippocampal theta interacts with higher frequency oscillations to support long‐term memory. Here we asked 10 presurgical epilepsy patients undergoing intracranial EEG recording to perform a long‐term spatial memory task in desktop virtual reality and found that increased theta power in two discrete bands (“low” 2‐5 Hz and “high” 6‐11 Hz) during cued retrieval was associated with improved task performance. Similarly, increased coupling between “low” theta phase and gamma amplitude during the same period was associated with improved task performance. Finally, low and high gamma amplitude appeared to peak at different phases of the theta cycle; providing a novel connection between human hippocampal function and rodent data. These results help to elucidate the role of theta oscillations and theta‐gamma phase‐amplitude coupling in human long‐term memory.

The findings of this study would support invasive prenatal diagnosis for an ultrasound finding of fetal cystic hygroma. Even in euploid pregnancies with cystic hygroma, there is a high mortality with associated abnormalities. The data also suggest a guarded pregnancy prognosis for the finding of fetal cystic hygroma, and that it is improved with spontaneous resolution, especially in male fetuses of normal karyotype.