Evidence for a persistent sodium conductance in neurons from the nucleus prepositus hypoglossi.

Intracellular recordings were made from 39 neurons in a slice preparation of the prepositus hypoglossi nucleus from guinea pigs. Morphological characteristics were confirmed by dying neurons with Lucifer yellow. The neurons were spontaneously active, firing in the range of 8-50 spikes/s. Spike duration was short (0.32 ms) and the spikes were followed by fast and slow afterhyperpolarizations. The current vs frequency relationship was linear during steady state firing, but showed dual firing ranges corresponding to the first, third and fifth interspike interval. The instantaneous frequency of the first few interspike intervals could reach 500 spikes/s. Depolarizing and hyperpolarizing responses to square pulses displayed initial sag and rebound responses sensitive to extracellular Cs+, pharmacologically classifying the responses as a result of a Q-like current. Substitution of Ca2+ in the medium with the inorganic calcium blockers Mn2+ or Co2+ resulted in oscillatory firing, depolarizing excursions being sensitive to tetrodotoxin (TTX). Mn2+ or Co2+ in combination with extracellular Cs+ elicited TTX-sensitive plateau potentials, blocked in Na+ -free solution. In conclusion, the prepositus neurons displayed spontaneous activity in the slice preparation and active membrane properties above as well as below the threshold of the action potential. In addition, the prepositus neurons possess a persistent sodium conductance that can be uncovered by inorganic calcium blockers. It may be involved in sustaining the spontaneous discharge.

Dexamethasone suppression test, TRH test and Newcastle II depression rating in the diagnosis of depressive disorders.

The dexamethasone suppression test (DST), the thyrotropin releasing hormone (TRH) test and the Newcastle II depression rating (NII) were compared with the clinical diagnosis and evaluated in 61 patients fulfilling the criteria of an affective disorder according to the DSM-III classification. A statistically significant correlation between clinical diagnosis and DST as well as NII, but not between clinical diagnosis and TRH test, was found. There was no correlation between DST and the severity of depression according to the Hamilton depression rating. The nosographic and the diagnostic specificities and sensitivities for the DST, TRH test and NII and DST and NII, a nosographic sensitivity of 50% and a nosographic specificity of 84% were found. Correspondingly, the diagnostic sensitivity was 43% and the diagnostic specificity was 88%. The DST and the TRH test were found of no value in the prediction of the response to antidepressive treatment. Mainly because of a low diagnostic sensitivity the NII, the DST and the TRH test are of limited value in the diagnosis of depressive disorders.

Programmed electromyographic activity and negative incremental muscle stiffness in monkeys jumping downward.

We trained monkeys to jump down from different heights, and recorded electromyograms (e.m.g.s) in arm muscles, and ground reaction forces. The landing movements were also recorded by high-speed cinematography. The e.m.g. of the triceps began about 80 ms before landing. The initial burst lasted until about 20 ms after ground contact and was succeeded by bursts of gradually declining amplitude. These discharges were not of reflex origin, because when the monkey was deceived by a collapsible platform, they were time-locked to the expected, not to the true landing. The amplitude of the e.m.g. in the triceps increased with the height of the jump, indicating adaptive control. The timing of the e.m.g. pattern was assumed to be programmed before take off, because it was unaffected by extinction of the light during the fall. The vertical ground reaction force produced by the arms had an inflexion on its rising phase which arose from the very rapid stretch of the muscles which control the wrist. Then came a sharp peak produced mainly by stretch of the triceps. The inflexion and the sharp peak were probably produced by short-range stiffness of the muscles of the upper arm. The torque acting on the elbow joint, and the elbow joint stiffness were calculated from the ground reaction forces and the movement of the arm. The torque was high at impact and gradually declined during the landing. The force produced by the triceps increased sharply, then decreased while it continued to lengthen. Thus, the elbow joint showed high initial stiffness, which then decreased, and finally became negative. This dynamic relation between length and tension was very different from the static length-tension characteristic of skeletal muscles. The observed behaviour of the muscles presumably takes advantage of the resistance of the musculo-skeletal system to transient forces. The observed negative stiffness occurs only during submaximal contractions. We propose that the segmented pattern in the e.m.g. produces submaximal contractions in both slow and fast fibres in spite of a high excitatory drive.

A lasting impairment in circle-ellipse discrimination after inferotemporal lesions in monkeys.

Monkeys with bilateral lesions in the inferotemporal cortex learn and relearn visual discrimination problems slowly, but previous studies have not settled the question of whether they, in addition, have a lasting deficit. I have trained monkeys to discriminate a circle from ellipses on a titration schedule and they produced the same thresholds as previously found in young humans. After incomplete inferotemporal lesions the monkeys were retrained in 10,000 trials during one year. Thresholds were impaired in 3 of 5 monkeys with no tendency to improvement during the last 6 months. Neither the transient nor the lasting deficit occurred after control lesions in the superior temporal gyrus. The small lasting deficit was not owing to geniculo-striate damage; in addition to histological evidence only striate lesions increased choice reaction times. The small lasting deficit is compatible with the hypothesis, that the visual system contains a hierarchy of sequential feature detectors.

The dendritic response to GABA in CA1 of the hippocampal slice.

Application of GABA in the dendritic region of pyramidal cells elicits a depolarization which, in fact, is the sum of a hyperpolarizing and a depolarizing process. At the reversal potential of the depolarizing response (-42 mV) the GABA-induced current fluctuations do not have a minimum. Consequently, a conductance change to more than one ion is involved. Cl- is in part responsible, Ca2+ is not because Mn2+ and Mg2+ do not change the response. Whether Na+ is involved is uncertain. Substitution with choline had no effect but choline may permeate through the membrane during the depolarizing response. Nipecotic acid inhibits a Na+-GABA uptake mechanism but does not change the dendritic response.

Two different responses of hippocampal pyramidal cells to application of gamma-amino butyric acid.

1. Extra- and intracellular recordings were made from CA1 cells in hippocampal slices in vitro. The effects of ionophoretically applied GABA on somatic and dendritic regions were studied. 2. Ionophoresis of GABA at dendritic sites gave a reciprocal effect by inhibiting the effect of excitatory synapses close to the dendritic application, while facilitating those lying further away. For example, GABA delivered to the mid-radiatum dendritic region reduced the population spike generated by a radiatum volley, while facilitating the population spike evoked by oriens fibre stimulation. Similarly, when single cells were recorded from, mid-apical dendritic delivery of GABA abolished the synaptically driven discharges evoked by fibres terminating at this part of the dendritic tree, but facilitated the responses to input from fibres terminating on the basal dendrites of the same cell. 3. With intracellular recording two effects were observed. Applied near the soma, GABA induced a hyperpolarization associated with an increased membrane conductance. When applied to dendrites, GABA caused a depolarization also associated with an increased membrane conductance. Both types of GABA applications could inhibit cell discharges, although in some cases the depolarizing response could facilitate other excitatory influences or cause cell firing by itself. 4. Both the hyperpolarizing and depolarizing GABA responses persisted after blockade of synaptic transmission by applying a low calcium high magnesium solution, indicating mediation via a direct effect upon the cell membrane. 5. The reversal potential for the hyperpolarizing GABA effect was similar to the equilibrium potential for the i.p.s.p. evoked from alveus or orthodromically, and was 10-12 mV more negative than the resting potential. The size of the depolarizing response was also dependent upon the membrane potential. By extrapolation an estimated equilibrium potential was calculated as about -40 mV. 6. Our results support the idea that the hyperpolarizing basket cell inhibition at the soma is mediated by the release of GABA. This hyperpolarizing response causes a general inhibition of firing. The dendritic effects of GABA, however, seem to represent another type of inhibition, which by shunting synaptic currents makes possible a selective inhibitory influence on afferents synapsing locally while facilitating more remotely placed excitatory synapses. We propose the term discriminative inhibition for this postulated new type of control of pyramidal cell discharges.

Infantile vaginal tumour with alpha-fetoprotein synghesis.

A 17-month-old girl with a vaginal embryonal carcinoma (germ cell tumour) is reported. Alpha-fetoprtoein (AFP) was elevated before treatment in blood and vaginal fluid. Normal levels of AFP in blood and vaginal fluid were found after radiation and comination chemotherapy. By an indirect immunoperoxidase staining AFP was demonstrated in tumour tissue. 24-month-old local recurrence was preceded by a slight increase in serum AFP, and AFP could also be demonstrated in vaginal fluid and vaginal smears.

Task dependence of slowing after pyramidal lesions in monkeys.

The effect of lesions in a medullary pyramid was studied in two experiments. (a) Monkeys were trained to press a key with a rear-projected circle, presented together with different numbers of keys with ellipses. Two to eight choices were presented in a random sequence. Discrimination was measured with a titration schedule, and short choice reaction times were reinforced selectively. Choice reaction time and the function relating it to the number of choices were unaffected by lesions reducing the area of a transverse section of the pyramid up to 93%. (b) A repetitive response controlled by a fixed-ratio schedule was performed simultaneously with a holding response with the other hand, and the two hands changed function after each food pellet. Lesions reducing the pyramid only 25% increased interresponse times of the phasic response with the contralateral hand. Experiment 1 and previous studies are interpreted to indicate that slowing after pyramidal lesions is dependent on behavioral context. Experiment 2 showed that a simple repetitive movement is affected when the rate is high. The static response was more clearly affected than the phasic response, which indicates a role for the pyramidal tract in posture.

Course in basic sexology for medical students.

The present article describes the pilot course in basic sexology for medical students. The duration of the course was 5 days (35 hours). The themes-sex and gender, sexual physiology, contraception, sexual inadequacy, sexual deviations, and sexual counselling-were approached from many different angles. The teaching procedure comprised lectures, group work, and group discussions, internal television, films, plenary discussions, and debates. The course was evaluated by means of the sex knowledge and attitude test (SKAT) given before and after the course. Furthermore an evaluation was given by the students, by a professional teacher, and by a paramedical evaluator at the end of the course. The results showed significant changes in attitudes and knowledge.

Post-reinforcement pauses and response rate of monkeys on a two-hand fixed-ratio schedule.

Fixed-ratio behavior of monkeys was analyzed separately for two hands. While one hand responded on the fixed-ratio schedule the other performed a holding response and the function of the hands changed in alternate ratio runs. After performance was stable on the fixed ratio (70 responses, two monkeys; 100 responses, two monkeys, 120 responses, two monkeys) 90 sessions of further training equalized post-reinforcement pauses and the mean interresponse time of the two hands. Hand preference in reaching for food remained unchanged. Then, the fixed-ratio requirement was changed (a) in small sequential steps, (b) in two large steps, and, (c) within sessions alternating two runs at a high ratio with two runs at a low ratio. The mean duration of post-reinforcement pauses was correlated with a fixed ratio maintained throughout a session but single pauses were neither controlled by the immediately preceding nor by the following ratio run when a cue to its length was available. The mean interresponse time was insensitive to changes in fixed ratio. The fixed-ratio performance was generally similar to that of pigeons and rats.