Mary Kate Worden

Why are medical students ‘checking out’ of active learning in a new curriculum?

The University of Virginia School of Medicine recently transformed its pre‐clerkship medical education programme to emphasise student engagement and active learning in the classroom. As in other medical schools, many students are opting out of attending class and others are inattentive while in class. We sought to understand why, especially with a new student‐centred curriculum, so many students were still opting to learn on their own outside of class or to disengage from educational activities while in class.

Temperature dependence of cardiac performance in the lobster Homarus americanus.

SUMMARY The lobster Homarus americanus inhabits ocean waters that vary in temperature over a 25°C range, depending on the season and water depth. To investigate whether the lobster heart functions effectively over a wide range of temperatures we examine the temperature dependence of cardiac performance of isolated lobster hearts in vitro. In addition, we examined whether modulation of the heart by serotonin depends on temperature. The strength of the heartbeat strongly depends on temperature, as isolated hearts are warmed from 2 to 22°C the contraction amplitude decreases by greater than 60%. The rates of contraction and relaxation of the heart are most strongly temperature dependent in the range from 2 to 4°C but become temperature independent at warmer temperatures. Heart rates increase as a function of temperature both in isolated hearts and in intact animals, however hearts in intact animals beat faster in the temperature range of 12–20°C. Interestingly, acute Q10 values for heart rate are similar in vivo and in vitro over most of the temperature range, suggesting that temperature dependence of heart rate arises mainly from the temperature effects on the cardiac ganglion. In contrast to earlier reports suggesting that the strength and the frequency of the lobster heartbeat are positively correlated, we observe no consistent relationship between these parameters as they change as a function of temperature. Stroke volume decreases as a function of temperature. However, the opposing temperature-dependent increase in heart rate partially compensates to produce a relationship between cardiac output and temperature in which cardiac output is maximal at 10°C and significantly decreases above 20°C. Serotonin potentiates contraction amplitude and heart rate in a temperature-independent manner. Overall, our results show that although the parameters underlying cardiac performance show different patterns of temperature dependence, cardiac output remains relatively constant over most of the wide range of environmental temperatures the lobster inhabits in the wild.

Modulation of vertebrate and invertebrate neuromuscular junctions

Advances in our understanding of how the neuromuscular junction is modulated include an expanded appreciation of the many different types of modulatory influences, from soluble factors to second-messenger systems, to specific proteins in nerve and muscle. Recent studies indicate that modulation of neuromuscular function is effected on both the presynaptic and postsynaptic sides of the neuromuscular junction.

Evaluation of quantal neurosecretion from evoked and miniature postsynaptic responses by deconvolution method

A new deconvolution algorithm has been developed for evaluation of quantal content and its variability at high-output synapses. The algorithm derives the distribution of the number of neurosecretory quanta released in a trial (M) from the measured sizes of evoked postsynaptic responses. The deconvolution employs the distribution of quantal sizes obtained by measuring sizes of miniature postsynaptic responses. The distribution of quantal content M is derived by ridge regression method from the distributions of sizes of the responses and of quantal sizes. The deconvolution method was applied to postsynaptic responses from the excitory innervation of lobster dactyl opener muscle obtained by focal extracellular recordings. The obtained solution (distribution of M) had six to eight components and was stable. The method was tested by the analysis of simulated multiquantal responses. For the simulated responses, the ridge regression solution reproduced the imposed distribution of M within the limits of the calculated confidence intervals. To further test the algorithm, the distribution of M at a low-output synapse was obtained both by deconvolution method and by the method of direct quantal counts. The results of these two methods were found to be in a very good agreement.

An algorithm for high-resolution detection of postsynaptic quantal events in extracellular records

A software package has been developed for the detection and measurement of extracellularly recorded postsynaptic quantal events evoked by neural stimulation. The algorithm is based on the identification of monotonic regions of a differentiated current signal and detects the small inflections and peaks of a postsynaptic response that result from the asynchronous presynaptic release of individual packets of neurotransmitter. Recorded and simulated postsynaptic responses have been used to verify the accuracy of the algorithm and to determine its resolution. The algorithm can accurately detect up to six individual quanta in a time period of 20 ms, with a resolution of 0.5-1.0 ms.

Temperature and acid–base balance in the American lobster Homarus americanus

Lobsters (Homarus americanus) in the wild inhabit ocean waters where temperature can vary over a broad range (0–25°C). To examine how environmental thermal variability might affect lobster physiology, we examine the effects of temperature and thermal change on the acid–base status of the lobster hemolymph. Total CO2, pH, PCO2 and HCO –3 were measured in hemolymph sampled from lobsters acclimated to temperature in the laboratory as well as from lobsters acclimated to seasonal temperatures in the wild. Our results demonstrate that the change in hemolymph pH as a function of temperature follows the rule of constant relative alkalinity in lobsters acclimated to temperature over a period of weeks. However, thermal change can alter lobster acid–base status over a time course of minutes. Acute increases in temperature trigger a respiratory compensated metabolic acidosis of the hemolymph. Both the strength and frequency of the lobster heartbeat in vitro are modulated by changes in pH within the physiological range measured in vivo. These observations suggest that changes in acid–base status triggered by thermal variations in the environment might modulate lobster cardiac performance in vivo.

Stochastic Modeling of Facilitated Neurosecretion

Two models of neurosecretion were evaluated in terms of their ability to predict the dependency of quantal content (m) on the frequency of repetitive stimulation of a lobster motoneuron. First, the hypothesis that neurosecretion is limited by a fixed number of release sites was tested by the fit of the distribution of m by uniform and nonuniform binomial statistics. The obtained release probabilities suggest that frequency facilitation can be due to activation of a group of sites with high release probabilities. However, the fit obtained using this model is not statistically significant due to a large number of fitting parameters. Second, the hypothesis that neurosecretion is limited by the rates of exchange between the releasable pool and the total store of quanta and that each stimulus enhances quantal mobilization was tested. Monte Carlo simulation was carried out in accordance with this model and reproduced the observed distribution of m with very few fitting parameters and therefore with a high level of significance (>0.1). This result demonstrates that mobilization of extra vesicles with each stimulus is a mechanism that allows a very accurate and parsimonious quantitative description of frequency facilitation.

Neuromuscular synapses on the dactyl opener muscle of the lobster Homarus americanus.

The crustacean dactyl opener neuromuscular system has been studied extensively as a model system that exhibits several forms of synaptic plasticity. We report the ultrastructural features of the synapses on dactyl opener of the lobster (Homarus americanus) as determined by examination of serial thin sections. Several innervation sites supplied by an inhibitory motoneuron have been observed without nearby excitatory innervation, indicating that excitatory and inhibitory inputs to the muscle are not always closely matched. The ultrastructural features of the lobster synapses are generally similar to those described previously for the homologous crayfish muscle, with one major distinction: few dense bars are seen at the presynaptic membranes of these lobster synapses. The majority of the lobster neuromuscular synapses lack dense bars altogether, and the mean number of dense bars per synapse is relatively low. In view of the finding that the physiology of the lobster dactyl opener synapses is similar to that reported for crayfish, these ultrastructural observations suggest that the structural complexity of the synapses may not be a critical factor determining synaptic plasticity.

Active learning, the accreditation process and 20-something students.

Editor – As the authors of ‘Why are medical students ‘checking out’ of active learning in a new curriculum?’, we thank Liz Mossop for her accompanying commentary ‘The curse of the teenage learner’. We appreciate her characterisation of our study as ‘frank and honest’ and agree that helping students to reflect on their learning styles and abilities is important for their professional development. This process is a formal component of our orientation activities for new students.

Presynaptic facilitation: Quantal analysis and simulations ☆

Abstract The time-course of quantal neurosecretion indicated asynchrony in releases of presynaptic vesicles (quanta) in response to a stimulus. This was interpreted as reflecting the sequential release of vesicles from a single release site. We performed Monte-Carlo simulation of facilitated neurosecretion based upon the hypothesis that release sites do not limit transmitter release. The output of this simulation succeeded in reproducing the experimentally obtained distribution of quantal releases. These results support a model for neurosecretion in which each action potential evokes mobilization of synaptic vesicles to a single presynaptic release site followed by probabilistic secretion of releasable vesicles one after another.