Metabolic response of auditory brainstem neurons to their broad physiological activity range.

Neurons exhibit a high energetic need, and the question arises as how they metabolically adapt to changing activity states. This is relevant for interpreting functional neuroimaging in different brain areas. Particularly, neurons with a broad firing range might exhibit metabolic adaptations. Therefore, we studied MNTB (medial nucleus of the trapezoid body) principal neurons, which generate action potentials (APs) at frequencies up to several hundred hertz. We performed the experiments in acute brainstem slices of the Mongolian gerbil (Meriones unguiculatus) at 22.5-24.5°C. Upon electrical stimulation of afferent MNTB fibres with 400 stimuli at varying frequencies, we monitored autofluorescence levels of NAD(P)H and FAD and determined the extremum amplitudes of their biphasic response. Additionally, we compared these data with alterations in O2 concentrations measured with an electrochemical sensor. These O2 changes are prominent since MNTB neurons rely on oxidative phosphorylation as shown by our pharmacological experiments. We calculated the O2 consumption rate as change in O2 concentration divided by stimulus durations, because these periods varied inversely with stimulus frequency as a result of the constant number of 400 stimuli applied. The O2 consumption rate increased with stimulation frequency up to a constant value at 600 Hz; that is, energy demand depends on temporal characteristics of activity despite the same number of stimuli. The rates showed no correlation with peak amplitudes of NAD(P)H or FAD, whilst the values of the two molecules were linearly correlated. This points at the complexity of analysing autofluorescence imaging for quantitative metabolic studies, because these values report only relative net changes of many superimposed oxidative and reductive processes. Monitoring O2 concentration rates is, thus, an important tool to improve the interpretation of NAD(P)H/FAD autofluorescence data, as they do not under all conditions and in all systems appropriately reflect the metabolic activity or energy demand.

An Active Sensing Paradigm for Studying Human Auditory Perception.

Our perception is based on active sensing, i.e., the relationship between self-motion and resulting changes to sensory inputs. Yet, traditional experimental paradigms are characterized by delayed reactions to a predetermined stimulus sequence. To increase the engagement of subjects and potentially provide richer behavioral responses, we developed Sensory Island Task for humans (SITh), a freely-moving search paradigm to study auditory perception. In SITh, subjects navigate an arena in search of an auditory target, relying solely on changes in the presented stimulus frequency, which is controlled by closed-loop position tracking. A "target frequency" was played when subjects entered a circular sub-area of the arena, the "island", while different frequencies were presented outside the island. Island locations were randomized across trials, making stimulus frequency the only informative cue for task completion. Two versions of SITh were studied: binary discrimination, and gradual change of the stimulus frequency. The latter version allowed determining frequency discrimination thresholds based on the subjects' report of the perceived island location (i.e., target frequency). Surprisingly, subjects exhibited similar thresholds as reported in traditional "stationary" forced-choice experiments after performing only 30 trials, highlighting the intuitive nature of SITh. Notably, subjects spontaneously employed a small variety of stereotypical search patterns, and their usage proportions varied between task versions. Moreover, frequency discrimination performance depended on the search pattern used. Overall, we demonstrate that the use of an ecologically driven paradigm is able to reproduce established findings while simultaneously providing rich behavioral data for the description of sensory ethology.