Patterns of Domain-Specific Learning Among Medical Undergraduate Students in Relation to Confidence in Their Physiology Knowledge: Insights From a Pre-post Study.

RESEARCH FOCUS: The promotion of domain-specific knowledge is a central goal of higher education and, in the field of medicine, it is particularly essential to promote global health. Domain-specific knowledge on its own is not exhaustive; confidence regarding the factual truth of this knowledge content is also required. An increase in both knowledge and confidence is considered a necessary prerequisite for making professional decisions in the clinical context. Especially the knowledge of human physiology is fundamental and simultaneously critical to medical decision-making. However, numerous studies have shown difficulties in understanding and misconceptions in this area of knowledge. Therefore, we investigate (i) how preclinical medical students acquire knowledge in physiology over the course of their studies and simultaneously gain confidence in the correctness of this knowledge as well as (ii) the interrelations between these variables, and (iii) how they affect the development of domain-specific knowledge. METHOD: In a pre-post study, 169 medical students' development of physiology knowledge and their confidence related to this knowledge were assessed via paper-pencil questionnaires before and after attending physiology seminars for one semester. Data from a longitudinal sample of n = 97 students were analyzed using mean comparisons, regression analyses, and latent class analyses (LCAs). In addition, four types of item responses were formed based on confidence and correctness in the knowledge test. RESULTS: We found a significant and large increase in the students' physiology knowledge, with task-related confidence being the strongest predictor (apart from learning motivation). Moreover, a significantly higher level of confidence at t2 was confirmed, with the level of prior confidence being a strong predictor (apart from knowledge at t2). Furthermore, based on the students' development of knowledge and confidence levels between measurement points, three empirically distinct groups were distinguished: knowledge gainers, confidence gainers, and overall gainers. The students whose confidence in incorrect knowledge increased constituted one particularly striking group. Therefore, the training of both knowledge and the ability to critically reflect on one's knowledge and skills as well as an assessment of their development in education is required, especially in professions such as medicine, where knowledge-based decisions made with confidence are of vital importance.

Undergraduate Students' Critical Online Reasoning-Process Mining Analysis.

To successfully learn using open Internet resources, students must be able to critically search, evaluate and select online information, and verify sources. Defined as critical online reasoning (COR), this construct is operationalized on two levels in our study: (1) the student level using the newly developed Critical Online Reasoning Assessment (CORA), and (2) the online information processing level using event log data, including gaze durations and fixations. The written responses of 32 students for one CORA task were scored by three independent raters. The resulting score was operationalized as "task performance," whereas the gaze fixations and durations were defined as indicators of "process performance." Following a person-oriented approach, we conducted a process mining (PM) analysis, as well as a latent class analysis (LCA) to test whether-following the dual-process theory-the undergraduates could be distinguished into two groups based on both their process and task performance. Using PM, the process performance of all 32 students was visualized and compared, indicating two distinct response process patterns. One group of students (11), defined as "strategic information processers," processed online information more comprehensively, as well as more efficiently, which was also reflected in their higher task scores. In contrast, the distributions of the process performance variables for the other group (21), defined as "avoidance information processers," indicated a poorer process performance, which was also reflected in their lower task scores. In the LCA, where two student groups were empirically distinguished by combining the process performance indicators and the task score as a joint discriminant criterion, we confirmed these two COR profiles, which were reflected in high vs. low process and task performances. The estimated parameters indicated that high-performing students were significantly more efficient at conducting strategic information processing, as reflected in their higher process performance. These findings are so far based on quantitative analyses using event log data. To enable a more differentiated analysis of students' visual attention dynamics, more in-depth qualitative research of the identified student profiles in terms of COR will be required.

Group III metabotropic glutamate receptors inhibit startle-mediating giant neurons in the caudal pontine reticular nucleus but do not mediate synaptic depression/short-term habituation of startle.

Short-term habituation is a basic form of learning that is analyzed in different species and using different behavioral models. Previous studies on mechanisms of short-term habituation yielded evidence for a potential role of group III metabotropic glutamate receptors (mGluRIIIs). Here we tested the hypothesis that mGluRIII mediate short-term habituation of startle in rats, combining electrophysiological experiments in vitro with behavioral studies in vivo. We applied different mGluRIII agonists and antagonists on rat brainstem slices while recording from startle-mediating neurons in the caudal pontine reticular nucleus (PnC) and monitoring synaptic depression presumably underlying habituation. Furthermore, we injected the mGluRIII antagonist (RS)-alpha-phosphonophenylglycine (MPPG) and the agonist L-(+)-2-amino-4-phosphonobutyric acid (L-AP4) into the PnC of rats in vivo and measured its effect on startle habituation. Our results show that activation of mGluRIIIs in the PnC strongly inhibits startle-mediating giant neurons in vitro. Accordingly, L-AP4 reduced startle responses in vivo. However, synaptic depression in the slice was not disrupted by mGluRIII antagonists or agonists. Correspondingly, the in vivo application of the mGluRIII antagonist MPPG failed to show any effect on short-term habituation of startle responses. We therefore conclude that mGluRs are expressed within the primary startle pathway and that they inhibit startle responses upon activation; however, this inhibition does not play any role in synaptic depression and short-term habituation of startle. This is in contrast to the role of mGluRIIIs in other forms of habituation and supports the notion that there are different mechanisms involved in habituation of sensory-evoked behaviors.

Excitability of pontine startle processing neurones is regulated by the two-pore-domain K+ channel TASK-3 coupled to 5-HT2C receptors.

The mammalian startle reflex is a fast response to sudden intense sensory stimuli that can be increased by anxiety or decreased by reward. The cellular integration of sensory and modulatory information takes place in giant neurones of the caudal pontine reticular formation (PnC). The startle reflex is known to be enhanced by 5-hydroxytryptamine (5-HT); however, signalling mechanisms that change the excitability of the PnC giant neurones are poorly understood. Possible molecular candidates are two-pore-domain K(+) (K(2)P) channels that generate a variable K(+) background conductance and control neuronal excitability upon activation of G-protein-coupled receptors. We demonstrate by in situ hybridization that the K(2)P channel TASK-3 is substantially expressed in PnC giant neurones. Brain slice recordings revealed a corresponding background K(+) current in these cells that forms about 30% of the outward current at -30 mV. Inactivation of TASK-3 at pH 6.4 and by ruthenium red depolarized the cells by about 7 mV and increased the action potential frequency as well as duration. Specific activation of Galpha(q)-coupled 5-HT(2) receptors with alpha-methyl 5-HT evoked a similar increase of neuronal excitability. Consistently, we measured afferent synaptic inputs from serotonergic raphe neurones and detected 5-HT(2C) receptors in PnC giant neurones by immunohistochemistry. Thus, neuronal excitability of PnC giant neurones in vivo is most likely increased by serotonergic projections via the K(2)P channel TASK-3.

TRESK two-pore-domain K+ channels constitute a significant component of background potassium currents in murine dorsal root ganglion neurones.

TRESK (TWIK-related spinal cord K(+) channel) is the most recently identified member of the two-pore-domain potassium channel (K(2P)) family, the molecular source of background potassium currents. Human TRESK channels are not affected by external acidification. However, the mouse orthologue displays moderate pH dependence isolated to a single histidine residue adjacent to the GYG selectivity filter. In the human protein, sequence substitution of tyrosine by histidine at this critical position generated a mutant that displays almost identical proton sensitivity compared with mouse TRESK. In contrast to human TRESK, which is specifically located in spinal cord, we detected mouse TRESK (mTRESK) mRNA in several epithelial and neuronal tissues including lung, liver, kidney, brain and spinal cord. As revealed by endpoint and quantitative RT-PCR, mTRESK channels are mainly expressed in dorsal root ganglia (DRG) and on the transcript level represent the most important background potassium channel in this tissue. DRG neurones of all sizes were labelled by in situ hybridizations with TRESK-specific probes. In DRG neurones of TRESK[G339R] functional knock-out (KO) mice the standing outward current IK(so) was significantly reduced compared with TRESK wild-type (WT) littermates. Different responses to K(2P) channel regulators such as bupivacaine, extracellular protons and quinidine corroborated the finding that approximately 20% of IK(so) is carried by TRESK channels. Unexpectedly, we found no difference in resting membrane potential between DRG neurones of TRESK[WT] and TRESK[G339R] functional KO mice. However, in current-clamp recordings we observed significant changes in action potential duration and amplitude of after-hyperpolarization. Most strikingly, cellular excitability of DRG neurones from functional KO mice was significantly augmented as revealed by reduced rheobase current to elicit action potentials.

Synaptic depression and short-term habituation are located in the sensory part of the mammalian startle pathway.

BACKGROUND: Short-term habituation of the startle response represents an elementary form of learning in mammals. The underlying mechanism is located within the primary startle pathway, presumably at sensory synapses on giant neurons in the caudal pontine reticular nucleus (PnC). Short trains of action potentials in sensory afferent fibers induce depression of synaptic responses in PnC giant neurons, a phenomenon that has been proposed to be the cellular correlate for short-term habituation. We address here the question whether both this synaptic depression and the short-term habituation of the startle response are localized at the presynaptic terminals of sensory afferents. If this is confirmed, it would imply that these processes take place prior to multimodal signal integration, rather than occurring at postsynaptic sites on PnC giant neurons that directly drive motor neurons. RESULTS: Patch-clamp recordings in vitro were combined with behavioral experiments; synaptic depression was specific for the input pathway stimulated and did not affect signals elicited by other sensory afferents. Concordant with this, short-term habituation of the acoustic startle response in behavioral experiments did not influence tactile startle response amplitudes and vice versa. Further electrophysiological analysis showed that the passive properties of the postsynaptic neuron were unchanged but revealed some alterations in short-term plasticity during depression. Moreover, depression was induced only by trains of presynaptic action potentials and not by single pulses. There was no evidence for transmitter receptor desensitization. In summary, the data indicates that the synaptic depression mechanism is located presynaptically. CONCLUSION: Our electrophysiological and behavioral data strongly indicate that synaptic depression in the PnC as well as short-term habituation are located in the sensory part of the startle pathway, namely at the axon terminals of sensory afferents in the PnC. Our results further corroborate the link between synaptic depression and short-term habituation of the startle response.

Neurons of the superior olivary complex do not excite startle-mediating neurons in the caudal pontine reticular formation.

The acoustic startle response is an important mammalian model for studying the cellular mechanisms of emotions and learning. Lesions in the superior olivary complex have been shown to attenuate the amplitude of the acoustic startle response, thus a substantial contribution of these neurons to the startle response was proposed. We here explored the putative connection of olivary neurons to the startle-mediating giant neurons in the reticular formation in rat brain slices in vitro. Tracing studies and electrical stimulation in the superior olivary complex revealed a strong connection; however it was not possible to distinguish between olivary neurons and traversing auditory fibres. Glutamate uncaging in the olivary complex excited a subpopulation of olivary neurons but never PnC giant neurons, as shown by patch-clamp recordings. This clearly contradicts an excitatory connection from olivary neurons to PnC giant neurons and thus an involvement of the superior olivary complex in eliciting a startle response.

Synaptic plasticity in the acoustic startle pathway: the neuronal basis for short-term habituation?

The aim of the present study was to analyse the cellular mechanism underlying short-term habituation of the acoustic startle response (ASR). We explored distinct synapses of the neuronal startle pathway in rat brain slices by patch-clamp recordings of giant neurons in the caudal pontine reticular formation. Presynaptic stimulation of auditory afferents by repeated bursts at 0.1 and 1 Hz led to an exponential decay of EPSC magnitudes. This homosynaptic depression (HSD) was reversible and repeatedly inducible after recovery. Many parameters of HSD in vitro match those of ASR habituation in vivo. The mechanisms underlying HSD are distinct from classical short-term plasticity: paired-pulse as well as paired-burst stimulation revealed a facilitation of the second EPSC, occurring in a much smaller time window up to interstimulus intervals of 200 ms. Pharmacological experiments demonstrated that HSD could be completely blocked by the group II and III metabotropic glutamate receptor antagonist MPPG. Similar results were obtained by CPPG, another group II and III antagonist. In contrast, HSD was not affected by the group I and II antagonist MCPG. We conclude that we found a form of synaptic depression in synapses within the primary startle pathway which correlates in many respects with short-term habituation of the ASR and which is presumably mediated by group III metabotropic glutamate receptors.