A lifetime’s adventure in extracellular K+ regulation: the Scottish connection

In a career that has spanned 45 years and shows no signs of slowing down, Dr Bruce Ransom has devoted considerable time and energy to studying regulation of interstitial K+. When Bruce commenced his studies in 1969 virtually nothing was known of the functions of glial cells, but Bruce’s research contributed to the physiological assignation of function to mammalian astrocytes, namely interstitial K+ buffering. The experiments that I describe in this review concern the response of the membrane potential (Em) of in vivo cat cortical astrocytes to changes in [K+]o, an experimental manoeuvre that was achieved in two different ways. The first involved recording the Em of an astrocyte while the initial aCSF was switched to one with different K+, whereas in the second series of experiments the cortex was stimulated and the response of the astrocyte Em to the K+ released from neighbouring neurons was recorded. The astrocytes responded in a qualitatively predictable manner, but quantitatively the changes were not as predicted by the Nernst equation. Elevations in interstitial K+ are not sustained and K+ returns to baseline rapidly due to the buffering capacity of astrocytes, a phenomenon studied by Bruce, and his son Chris, published 27 years after Bruce’s initial publications. Thus, a lifetime spent investigating K+ buffering has seen enormous advances in glial research, from the time cells were identified as ‘presumed’ glial cells or ‘silent cells’, to the present day, where glial cells are recognised as contributing to every important physiological brain function

Bursts and Isolated Spikes Code for Opposite Movement Directions in Midbrain Electrosensory Neurons

Directional selectivity, in which neurons respond strongly to an object moving in a given direction but weakly or not at all to the same object moving in the opposite direction, is a crucial computation that is thought to provide a neural correlate of motion perception. However, directional selectivity has been traditionally quantified by using the full spike train, which does not take into account particular action potential patterns. We investigated how different action potential patterns, namely bursts (i.e. packets of action potentials followed by quiescence) and isolated spikes, contribute to movement direction coding in a mathematical model of midbrain electrosensory neurons. We found that bursts and isolated spikes could be selectively elicited when the same object moved in opposite directions. In particular, it was possible to find parameter values for which our model neuron did not display directional selectivity when the full spike train was considered but displayed strong directional selectivity when bursts or isolated spikes were instead considered. Further analysis of our model revealed that an intrinsic burst mechanism based on subthreshold T-type calcium channels was not required to observe parameter regimes for which bursts and isolated spikes code for opposite movement directions. However, this burst mechanism enhanced the range of parameter values for which such regimes were observed. Experimental recordings from midbrain neurons confirmed our modeling prediction that bursts and isolated spikes can indeed code for opposite movement directions. Finally, we quantified the performance of a plausible neural circuit and found that it could respond more or less selectively to isolated spikes for a wide range of parameter values when compared with an interspike interval threshold. Our results thus show for the first time that different action potential patterns can differentially encode movement and that traditional measures of directional selectivity need to be revised in such cases

How does active substance use at psychiatric admission impact suicide risk and hospital length-of-stay?

Despite their high prevalence, little is known about the effects of substance use disorders and active substance use on the suicide risk or length-of-stay of psychiatric inpatients. This study examines the relationship between active substance use at the time of psychiatric hospitalization and changes in suicide risk measures and length-of-stay. Admission and discharge ratings on the Suicide Status Form-II-R, diagnoses, and toxicology data from 2,333 unique psychiatric inpatients were examined. Data for patients using alcohol, tetrahydrocannabinol, methamphetamines, cocaine, benzodiazepines, opiates, barbiturates, phencyclidine, and multiple substances on admission were compared with data from 1,426 admissions without substance use. Patients with substance use by toxicology on admission had a 0.9 day shorter length-of-stay compared to toxicology-negative patients. During initial nurse evaluation on the inpatient unit, these patients reported lower suicide measures (i.e., suicidal ideation frequency, overall suicide risk, and wish-to-die). No significant between-group differences were seen at discharge. Patients admitted with a substance use disorder diagnosis had a 1.0 day shorter length-of-stay than those without, while those with a substance use disorder diagnosis and positive toxicology reported the lowest measures of suicidality on admission. These results remained independent of psychiatric diagnosis. For acute psychiatric inpatients, suicide risk is higher and length-of-stay is longer in patients with substance use disorders who are NOT acutely intoxicated compared with patients without a substance use disorder. Toxicology-positive patients are less suicidal on admission and improve faster than their toxicology-negative counterparts. This study gives support to the clinical observation that acutely intoxicated patients may stabilize quickly with regard to suicidal urges and need for inpatient care