Robert L. Dunbar

IMAGING PARALLEL FIBER AND CLIMBING FIBER RESPONSES AND THEIR SHORT-TERM INTERACTIONS IN THE MOUSE CEREBELLAR CORTEX IN VIVO

A major question in the study of cerebellar cortical function is how parallel fiber and climbing fiber inputs interact to shape information processing. Emphasis has been placed on the long-term effects due to conjunctive stimulation of climbing fibers and parallel fibers. Much less emphasis has been placed on short-term interactions and their spatial nature. To address this question the responses to parallel fiber and climbing fiber inputs and their short-term interaction were characterized using optical imaging with Neutral Red in the anesthetized mouse in vivo. Electrical stimulation of the cerebellar surface evoked an increase in fluorescence consisting of a transverse optical beam. The linear relationship between the optical responses and stimulus parameters, high spatial resolution and close coupling to the electrophysiological recordings show the utility of this imaging methodology. The majority of the optical response was due to activation of postsynaptic alpha-amino-3-hydroxyl-5-methyl-4-isoxazole propionate (AMPA) and metabotropic glutamate receptors with a minor contribution from the presynaptic parallel fibers. Stimulation of the inferior olive evoked parasagittal bands that were abolished by blocking AMPA glutamate receptors. Conjunctive stimulation of the cerebellar surface and inferior olive resulted in inhibition of the climbing fiber evoked optical responses. This lateral inhibition of the parasagittal bands extended out from both sides of an activated parallel fiber beam and was mediated by GABA(A) but not GABA(B) receptors. One hypothesized role for lateral inhibition of this type is to spatially focus the interactions between parallel fiber and climbing fiber input on Purkinje cells. In summary optical imaging with Neutral Red permitted visualization of cerebellar cortical responses to parallel fiber and climbing fiber activation. The GABA(A) dependent lateral inhibition of the climbing fiber evoked parasagittal bands by parallel fiber stimulation shows that cerebellar interneurons play a short-term role in shaping the responses of Purkinje cells to climbing fiber input.

Optogenetic Visualization of Presynaptic Tonic Inhibition of Cerebellar Parallel Fibers.

Tonic inhibition was imaged in cerebellar granule cells of transgenic mice expressing the optogenetic chloride indicator, Clomeleon. Blockade of GABAA receptors substantially reduced chloride concentration in granule cells due to block of tonic inhibition. This indicates that tonic inhibition is a significant contributor to the resting chloride concentration of these cells. Tonic inhibition was observed not only in granule cell bodies, but also in their axons, the parallel fibers (PFs). This presynaptic tonic inhibition could be observed in slices both at room and physiological temperatures, as well as in vivo, and has many of the same properties as tonic inhibition measured in granule cell bodies. GABA application revealed that PFs possess at least two types of GABAA receptor: one high-affinity receptor that is activated by ambient GABA and causes a chloride influx that mediates tonic inhibition, and a second with a low affinity for GABA that causes a chloride efflux that excites PFs. Presynaptic tonic inhibition regulates glutamate release from PFs because GABAA receptor blockade enhanced both the frequency of spontaneous EPSCs and the amplitude of evoked EPSCs at the PF-Purkinje cell synapse. We conclude that tonic inhibition of PFs could play an important role in regulating information flow though cerebellar synaptic circuits. Such cross talk between phasic and tonic signaling could be a general mechanism for fine tuning of synaptic circuits. SIGNIFICANCE STATEMENT This paper demonstrates that an unconventional form of signaling, known as tonic inhibition, is found in presynaptic terminals and affects conventional synaptic communication. Our results establish the basic characteristics and mechanisms of presynaptic tonic inhibition and show that it occurs in vivo as well as in isolated brain tissue.

Fostering empathy in undergraduate health science majors through the reconciliation of objectivity and subjectivity: an integrated approach.

The demand for empathetic health care practitioners requires an academic curriculum suited to that need. Here we describe a series of integrated activities that were designed to foster empathy in undergraduate health science majors. By combining content and pedagogical approaches from the humanities and sciences, we asked students to reconcile objective and subjective modes of understanding the human body as a learning object. Preliminary evaluations of student behavior, written student responses, and survey results are offered as support for our conclusion that the integration of a humanities perspective into the Anatomy classroom at University of Minnesota Rochester can facilitate the process of developing student empathy through the reconciliation of objective and subjective modes. Furthermore, students were able to apply this understanding to images on the page or screen, to living human learning objects and human cadavers. Although to claim that these activities in themselves can stymie the stasis/decline of empathy that health science students report would be patently false, we conclude that similar approaches could offer an avenue by which other educators might develop similar activities that, in aggregate, might have a lasting effect from the undergraduate through the graduate level of training in the health sciences. Anat Sci Educ.

Student social self-efficacy, leadership status, and academic performance in collaborative learning environments

ABSTRACT Research confirms the positive effect of collaborative learning environments when students are considered as one homogeneous group. Little has been done to provide a detailed view of the performance of subgroups of students within collaborative settings. This quantitative and longitudinal study uses survey responses to explore differences in the variables of social self-efficacy (SSE) and leadership relative to each other, different academic performance levels, and across two academic years in a cohort of undergraduate students. Analysis showed no relationship between either sex or race and academic performance. However, results confirm that there is a positive relationship between SSE and grades, and that leaders have a higher SSE than followers. Results also show that SSE improves for leaders, but no evidence for such improvement for followers. We conclude that in collaborative learning environments, high SSE and leadership are important components in student achievement and should be considered when designing curricula.