Biology subjects

Hildebrandt, K. J.

Publications and source records attributed to Hildebrandt, K. J..

4 recordsLinked to original sources

bioRxiv2021

Differential optogenetic excitation of the auditory midbrain in freely moving behaving mice

In patients with severe sensory impairment due to compromised peripheral function, partial restoration can be achieved by implantation of sensory prostheses for the electrical stimulation of the central nervous system. However, these state of the art approaches suffer from the drawback of limited spectral resolution. Electrical field spread depends on the impedance of the surrounding medium, impeding spatially focused electrical stimulation in neural tissue. To overcome these technical limitations, optogenetic excitation could be applied in such prostheses to achieve enhanced resolution through precise and differential stimulation of nearby neuronal ensembles within the central sensory pathway. Previous experiments have provided a first proof for behavioral detectability of optogenetic excitation in the rodent auditory system. However, little is known about the generation of complex and behaviorally relevant sensory patterns involving differential excitation. In this study, we developed an optogenetic implant to excite two spatially separated points along the tonotopy of the murine central inferior colliculus (ICc). Using a newly-devised reward-based operant Go/No-Go paradigm for the evaluation of optogenetic excitation of the auditory midbrain in freely moving, behaving mice, we demonstrate that differential optogenetic excitation of a sub-cortical sensory pathway is possible and efficient. Here we demonstrate how animals which were previously trained in a frequency discrimination paradigm a) rapidly generalize between sound and optogenetic excitation, b) generally detect optogenetic excitation at two different neuronal ensembles, and c) discriminate between them. Our results demonstrate for the first time that optogenetic excitation at different points of the ICc tonotopy elicits a stable response behavior over time periods of several months. With this study, we provide the first proof of principle for sub-cortical differential stimulation of sensory systems using complex artificial cues in freely moving animals.

neuroscience↗

bioRxiv2019

Sustained Activation of PV+ Interneurons in Auditory Cortex Enables Robust Divisive Gain Control for Complex and Naturalistic Stimuli

Sensory cortices must flexibly adapt their operations to internal states and external requirements. Modulation of specific inhibitory interneurons may provide a network-level mechanism for adjustments on behaviourally relevant timescales. Understanding of the computational roles of such modulation has mostly been restricted to phasic optogenetic activation and short, transient stimuli. Here, we aimed to extend the understanding of modulation of cortical inhibition by using sustained, network-wide optogenetic activation of parvalbumin-positive interneurons in core auditory cortex to study modulation of responses to transient, sustained, and naturalistic stimuli. We found highly conserved spectral and temporal tuning, despite profoundly reduced overall network activity. This reduction was predominantly divisive, and consistent across simple, complex, and naturalistic stimuli. A recurrent network model with power-law input-output functions replicated our results. We conclude that modulation of parvalbumin-positive interneurons on timescales typical of more sustained neuromodulation may provide a means for robust divisive gain control conserving stimulus representations.

neuroscience↗

bioRxiv2019

Mice tune out not in: Violation of prediction drives auditory saliency

Successful navigation in complex acoustic scenes requires focusing on relevant sounds while ignoring irrelevant distractors. It has been argued that the ability to track stimulus statistics and generate predictions supports the choice what to attend and what to ignore. However, the role of these predictions about future auditory events in drafting decisions remains elusive. While most psychophysical studies in humans indicate that expected stimuli serve as implicit cues attracting attention, most work studying physiological auditory processing in animals highlights the detection of unexpected, surprising stimuli. Here, we tested whether in the mouse, target probability is used as an implicit cue attracting attention or whether detection is biased towards low-probability deviants using an auditory detection task. We implemented a probabilistic choice model to investigate whether a possible dependence on stimulus statistics arises from short term serial correlations or from integration over longer periods. Our results demonstrate that target detectability in mice decreases with increasing probability, contrary to humans. We suggest that mice indeed track probability over a time scale of at least several minutes but do not use this information in the same way as humans do: instead of maximizing reward by focusing on high-probability targets, the saliency of a target is determined by surprise.

animal behavior and cognition↗

bioRxiv2018

Ultra-fine temporal resolution in auditory processing is preserved in aged mice without peripheral hearing loss

Age-related hearing loss (presbycusis) is caused by damage to the periphery as well as deterioration of central auditory processing. Gap detection is a paradigm to study age-related temporal processing deficits, which is assumed to be determined primarily by the latter. However, peripheral hearing loss is a strong confounding factor when using gap detection to measure temporal processing. In this study, we used mice from the CAST line, which is known to maintain excellent peripheral hearing, to rule out any contribution of peripheral hearing loss to gap detection performance. We employed an operant Go/No-go paradigm to obtain psychometric functions of gap in noise (GIN) detection at young and middle age. Besides, we measured auditory brainstem responses (ABR) and multiunit recordings in the auditory cortex (AC) in order to disentangle the processing stages of gap detection. We found detection thresholds around 0.6 ms in all measurement modalities. Detection thresholds did not increase with age. In the ABR, GIN stimuli are coded as onset responses to the noise that follows the gap, strikingly similar to the ABR of noise bursts in silence (NBIS). The simplicity of the neural representation of the gap together with the preservation of detection threshold in aged CAST mice suggests that GIN detection in the mouse is primarily determined by peripheral, not central processing.

neuroscience↗