Seiler, J. P.- H. | bioRxiv Science

bioRxiv2026

Boredom and the representation of information content in the neocortex

Boredom - a pervasive mental state - promotes the pursuit of novel information by assigning negative value to monotonous conditions. Yet, how the brain extracts and represents the information content of ongoing sensory experience remains poorly understood. Here, we combine behavioral assays, neurophysiological recordings and computational modeling across humans and mice to investigate how sensory information shapes boredom-related behavior. In a cross-species choice task, both humans and mice robustly avoid monotonous sources of sensory stimulation. We formalize perceived monotony using empirical entropy as a measure of information content and show that monotony avoidance scales directly with low entropy and in humans correlates with boredom experience. Human electroencephalography and mesoscopic calcium imaging in mice reveal that the recruitment of neocortical activity tracks stimulus entropy. Two-photon calcium imaging in the auditory cortex of mice further uncovers a stimulus-invariant population code for entropy, supported by neurons tuned to information content. A recurrent network model reproduced this code through an interplay of afferent depression and recurrent facilitation. Together, we demonstrate how the information content of sensory experience is represented in cortical population activity, providing a basis for boredom-related avoidance behavior. Thus, our findings link synaptic and neuronal dynamics to boredom, acting as a safeguard mechanism to ensure high information input to the brain.

neuroscience↗

bioRxiv2024

Revealing Acute Consequences of Rapid Protein Elimination at Individual Synapses using Auxin-Inducible Degron 2 Technology

A powerful approach to assess a protein of interest (POI) function is its specific elimination. Common knock-out and knock-down strategies, however, are protracted and often irreversible, challenging the assessment of acute or temporary consequences in the same cells and tissues. Here we describe the use of Auxin-Inducible Degron 2 (AID2) technology to study the real-time consequences of acute POI elimination in nerve cell synapses. We demonstrate its capacity in cultured neurons and in vivo to rapidly eliminate postsynaptic scaffold proteins fused at N-terminal, C-terminal, or nested sites to GFP derivatives or HaloTag. We show that acute PSD-95 or gephyrin elimination leads to the concomitant loss of AMPA or GABAA receptors at the same synapses, and that, surprisingly, acute GKAP, but not PSD-95 elimination reduces postsynaptic scaffold size. Our findings highlight the utility of AID2 technology for rapidly eliminating synaptic POIs and studying real-time consequences in the same neurons and synapses.

neuroscience↗