Biology subjects

Fritz, J. B.

Publications and source records attributed to Fritz, J. B..

3 recordsLinked to original sources

bioRxiv2026

Exercise Myokine Irisin Enables Behavioral Stress Resistance in Mice

Physical activity produces widespread benefits to physical and mental health, including protection against stress-related behavioral outcomes. However, the peripheral signals through which physical activity is translated into stress resistance remain incompletely understood. Irisin, an exercise-induced myokine cleaved from the transmembrane protein FNDC5 and released into circulation, has been implicated in improved cognition and neuroprotection, but its role in resistance to behavioral consequences of future adversity has not been examined. Here, we tested whether forced peripheral elevation of irisin is sufficient to protect against stress-induced behavioral outcomes. Adult male C57BL/6 mice received adeno-associated viral (AAV)-mediated peripheral expression of irisin or GFP control. AAV-irisin significantly increased circulating irisin levels, and six weeks later, mice were exposed to inescapable stress, a well-characterized model that produces anxiety-like behaviors, including reducing rodents natural inclination toward sociability. Elevated circulating irisin prevented the stress-induced reduction in social preference without altering general locomotor activity. Moreover, circulating irisin levels positively predicted individual differences in sociability. Additionally, peripheral irisin elevation increased brain-derived neurotrophic factor (Bdnf) expression, which also positively correlated with circulating irisin levels. Finally, we identified expression of the irisin receptor subunit integrin V within the dorsal raphe nucleus, a key brain region implicated in the behavioral outcomes of inescapable stress that is modulated by prior exercise. Together, these findings identify peripheral irisin as a mediator sufficient to confer resistance to future stress, even in the absence of physical activity. Significance StatementPhysical activity protects against the anxiety-like behavioral outcomes of future stress, but the peripheral mediators of this effect remain unclear. Here we show that forced peripheral elevation of circulating irisin, an exercise-induced myokine, is sufficient to produce behavioral stress resistance in mice. Irisin prevented the stress-induced reduction in social preference and positively correlated with individual differences in sociability. Forced expression of peripheral irisin also increased Bdnf expression in the brain, consistent with engagement of central neuroplasticity pathways that support adaptive behavioral responses. These findings demonstrate that an exercise-induced circulating factor can confer resistance to future stress, identifying irisin as a potential prophylactic target for stress-related mental health disorders.

neuroscience↗

bioRxiv2019

Adaptive efficient coding of correlated acoustic properties

Natural sounds such as vocalizations often have co-varying acoustic attributes where one acoustic feature can be predicted from another, resulting in redundancy in neural coding. It has been proposed that sensory systems are able to detect such covariation and adapt to reduce redundancy, leading to more efficient neural coding. Results of recent psychoacoustic studies suggest that, following passive exposure to sounds in which temporal and spectral attributes covaried in a correlated fashion, the auditory system adapts to efficiently encode the two co-varying dimensions as a single dimension, at the cost of lost sensitivity to the orthogonal dimension. Here we explore the neural basis of this psychophysical phenomenon by recording single-unit responses from primary auditory cortex (A1) in awake ferrets exposed passively to stimuli with two correlated attributes in the temporal and spectral domain similar to that utilized in the psychoacoustic experiments. We found that: (1) the signal-to-noise (SNR) ratio of spike rate coding of cortical responses driven by sounds with correlated attributes was reduced along the orthogonal dimension; while the SNR ratio remained intact along the exposure dimension; (2) Mutual information of spike temporal coding increased only along the exposure dimension; (3) correlation between neurons tuned to the two covarying attributes decreased after exposure; (4) these exposure effects still occurred if sounds were correlated along two acoustic dimensions, but varied randomly along a third dimension. These neurophysiological results are consistent with the Efficient Learning Hypothesis and may deepen our understanding of how the auditory system represents acoustic regularities and covariance. SignificanceIn the Efficient Coding (EC) hypothesis, proposed by Barlow in 1961, the neural code in sensory systems efficiently encodes natural stimuli by minimizing the number of spikes to transmit a sensory signal. Results of recent psychoacoustic studies are consistent with the EC hypothesis, showing that following passive exposure to stimuli with correlated attributes, the auditory system adapts so as to more efficiently encode the two co-varying dimensions as a single dimension. In the current neurophysiological experiments, using a similar stimulus design and experimental paradigm to the psychoacoustic studies of Stilp and colleagues (2010, 2011, 2012, 2016), we recorded responses from single neurons in the auditory cortex of the awake ferret, showing adaptive efficient neural coding of correlated acoustic properties.

neuroscience↗

bioRxiv2018

Neural Responses in Dorsal Prefrontal Cortex Reflect Proactive Interference during an Auditory Reversal Task

Task-related plasticity in the brain is triggered by changes in the behavioral meaning of sounds. We investigated plasticity in ferret dorsolateral frontal cortex (dlFC) during an auditory reversal task to study the neural correlates of proactive interference, i.e., perseveration of previously learned behavioral meanings that are no longer task-appropriate. Although the animals learned the task, target recognition decreased after reversals, indicating proactive interference. Frontal cortex responsiveness was consistent with previous findings that dlFC encodes the behavioral meaning of sounds. However, the neural responses observed here were more complex. For example, target responses were strongly enhanced, while responses to non-target tones and noises were weakly enhanced and strongly suppressed, respectively. Moreover, dlFC responsiveness reflected the proactive interference observed in behavior: target responses decreased after reversals, most significantly during incorrect behavioral responses. These findings suggest that the weak representation of behavioral meaning in dlFC may be a neural correlate of proactive interference.\n\nSignificance StatementNeural activity in prefrontal cortex (PFC) is believed to enable cognitive flexibility during sensory-guided behavior. Since PFC encodes the behavioral meaning of sensory events, we hypothesized that weak representation of behavioral meaning in PFC may limit cognitive flexibility. To test this hypothesis, we recorded neural activity in ferret PFC, while ferrets performed an auditory reversal task in which the behavioral meanings of sounds were reversed during experiments. The reversal task enabled us study PFC responses during proactive interference, i.e. perseveration of previously learned behavioral meanings that are no longer task-appropriate. We found that task performance errors increased after reversals while PFC representation of behavioral meaning diminished. Our findings suggest that proactive interference may occur when PFC forms weak sensory-cognitive associations.

neuroscience↗