Trying times for human insulin.

The introduction of human insulin to treat diabetics seemed straightforward. What can account for the problems that have followed?     

A disinhibitory microcircuit for associative fear learning in the auditory cortex

Learning causes a change in how information is processed by neuronal circuits. Whereas synaptic plasticity, an important cellular mechanism, has been studied in great detail, we know much less about how learning is implemented at the level of neuronal circuits and, in particular, how interactions between distinct types of neurons within local networks contribute to the process of learning. Here we show that acquisition of associative fear memories depends on the recruitment of a disinhibitory microcircuit in the mouse auditory cortex. Fear-conditioning-associated disinhibition in auditory cortex is driven by foot-shock-mediated cholinergic activation of layer 1 interneurons, in turn generating inhibition of layer 2/3 parvalbumin-positive interneurons. Importantly, pharmacological or optogenetic block of pyramidal neuron disinhibition abolishes fear learning. Together, these data demonstrate that stimulus convergence in the auditory cortex is necessary for associative fear learning to complex tones, define the circuit elements mediating this convergence and suggest that layer-1-mediated disinhibition is an important mechanism underlying learning and information processing in neocortical circuits.     

Re-analysis of radiation-induced specific locus mutations in the mouse.

A re-analysis of published data on mouse mutation rates induced by X and gamma rays suggests that the kinetics of induction can be analysed by fitting the data to a parabolic curve. We interpret this to mean that a substantial proportion of the induced mutations results from gross chromosomal changes such as deletions, some of which are one-track and some of which are two-track. This analysis is based on the assumption that the shape of the dose curve, which in the female is concave upward, reflects the manner in which the mutations are induced rather than representing a one-track (linear) curve whose shape has been modified by differential repair.     

A testis-specific lactate dehydrogenase in the pipid frog,Hymenochirus boettgeri

Summary Lactate dehydrogenase zymograms of mature testes ofHymenochirus boettgeri show in addition to the five isozymes composed of LDH-A and LDH-B subunits, a second 5-band system which is due to isozymes formed between LDH-A and a third subunit, LDH-C. These testis-specific LDH-C isozymes appear around 6 months after metamorphosis indicating that their expression is correlated with sexual maturity as is generally the case in mammals. This is the first report of a testis-specific LDH isozyme in a lower tetrapod; such isozymes have hitherto only been reported in mammals and in the pigeon.This study was supported by a grant from the Fond National Suisse de la Recherche Scientifique to H.R.K. We thank M. Sateur and F. Bourquin for their technical help.     

Releasable GABA in tubular epithelium of rat kidney

Summary The distribution of gamma-aminobutyric acid (GABA) in the rat kidney was examined by immunocytochemical techniques. GABA-like immunoreactivity (GABA-LI) was predominantly confined to the renal tubules, including the ascending parts of the distal tubules, and the loops of Henle, the collecting tubules and ducts, and the connective parts of the convoluted tubules. In GABA-positive cortical tubules, about half of the epithelial cells were labelled. The labelled cell type showed the ultrastructural features of principal cells. Depolarizing stimulation by ouabain and high K⁺ concentration evoked the efflux of endogenous GABA from kidney slices. The present findings, along with previous results, suggest that GABA released from renal tubular epithelium, and transported with the urine, might be involved in the modulation of contractility in the urinary tract.