# Neuronal mechanisms of novelty seeking > **NIH NIH R01** · WASHINGTON UNIVERSITY · 2024 · $388,750 ## Abstract PROJECT SUMMARY Behavioral experiments in humans and primates show that novel visual objects motivate behavior, by capturing attention and gaze, and promoting learning. Abnormalities in novelty seeking are associated with obsessive compulsive disorder, anxiety, depression, anhedonia and autism. But despite the importance of novel objects in our daily life, and the clinical relevance of novelty seeking, we lack an understanding of how primate brain circuits determine whether an object is novel, and how novelty signals control novelty-seeking. Previous studies reported that neurons in many brain areas respond differently to novel stimuli versus familiar stimuli. However, novel stimuli differ from familiar stimuli in many respects. For instance, novel stimuli are unexpected, deviate from recent experiences, and motivate behavior. Such broad and diverse impact of novelty on behavior not only highlights that it is critical to understand the neural mechanisms of novelty seeking, but also illustrates why it has been challenging to dissociate novelty signals from other types of neural signals, and therefore why it has been difficult to isolate how circuits utilize novelty to control motivated behavior. The hypotheses of the Aims are that (i) object novelty controls novelty seeking through a newly discovered anterior ventral medial temporal cortex (AVMTC) to zona incerta circuit, and (ii) single AVMTC neurons acquire novelty selectivity through a quantitatively definable algorithm that considers object recency and object unexpectedness to mediate novelty- related behaviors. Aim 1 will uncover the neural mechanisms that control motivated behavior to explore novel objects. We devised a new behavioral paradigm that measures monkeys’ eagerness to experience novel objects. Preliminary neurophysiological and causal experiments suggest that an understudied subthalamic region, the zona incerta (ZI), controls the motivation to seek and explore novel visual objects, and that this ZI function is distinct from other types of primary reward- and intrinsic- motivated behaviors, such as from the drive to obtain information about uncertain rewards. These assertions will be fully tested by contrasting the novelty functions of ZI with the habenula-dopamine pathway. We will also study how this circuit controls novelty seeking when novelty has extrinsic values (e.g., good or bad) and must be integrated into object valuation. Aim 2 will determine the mechanisms through which novelty responses arise in a wide range of primate brain circuits by recording single neurons’ activity across temporal cortex, amygdala, hippocampus, and the prefrontal cortices with semi chronic high channel count arrays while monkeys participate in a behavioral procedure that will (i) assess the underpinnings of single neurons’ object novelty responses, and will (ii) dissociate novelty responses from signed and unsigned subjective-value and prediction errors. These Aims offer an unprecedented opportuni... ## Key facts - **NIH application ID:** 10895322 - **Project number:** 5R01MH128344-03 - **Recipient organization:** WASHINGTON UNIVERSITY - **Principal Investigator:** Ilya E. Monosov - **Activity code:** R01 (R01, R21, SBIR, etc.) - **Funding institute:** NIH - **Fiscal year:** 2024 - **Award amount:** $388,750 - **Award type:** 5 - **Project period:** 2022-08-23 → 2025-06-30 ## Primary source NIH RePORTER: https://reporter.nih.gov/project-details/10895322 ## Citation > US National Institutes of Health, RePORTER application 10895322, Neuronal mechanisms of novelty seeking (5R01MH128344-03). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10895322. Licensed CC0. --- *[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*