RESEARCH
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Background
Background
When we first encounter a new stimulus, our brain responds strongly to the novel event. This heightened response to novelty increases attention and arousal, and enhances cognition by integrating neuronal responses that are crucial for assessing the potential significance of the new experience. This strong reaction, along with the habituation that occurs with repeated exposure, plays a key role in adapting to dynamic environments and supporting goal-directed behaviors. Disruptions in these processes are linked to a variety of neurodevelopmental and neuropsychiatric disorders, underscoring the importance of understanding the neurobiological and neuropathological mechanisms involved in novelty processing.
Research Goals
Research Goals
The primary goals of our research are to investigate: 1) the neuronal circuits and molecular mechanisms that govern responses to novelty and adaptive learning through repeated exposures; 2) how novelty circuits are disrupted in neurological disorders, their role in disease pathophysiology, and whether specifically targeting these circuits could offer a therapeutic strategy; and 3) the genetic components of novelty circuits and how these are influenced across the lifespan. To address these questions, we employ a multidisciplinary approach that spans behavioral, circuit, molecular, and genetic levels.
1. Behavioral and circuit elements guiding social novelty
1. Behavioral and circuit elements guiding social novelty
Social behaviors are dynamic, experience-driven motivational forces that are essential to our daily lives and community well-being. A key aspect of sociability is the ability to detect and respond to novel social cues, distinguishing them from familiar ones, an action selection mode that is often impaired in neurodevelopmental and neuropsychiatric disorders.
Our previous work (Molas et al., Nat Neurosci., 2017; Molas et al., Nat Commun., 2024) demonstrated that distinct molecular and circuit mechanisms coordinate differential responses to social novelty versus familiarity. Building on these foundations, the focus of our research is to map a comprehensive network of genetically identified neuronal circuits that orchestrate responses to social novelty.
From a more translational perspective, our research aims to understand how these neuronal networks are dynamically regulated in genetically predisposed mouse models of neurodevelopmental and neuropsychiatric disorders. Ultimately, our goal is to open new avenues for targeting and manipulating social novelty circuits to rescue core behavioral functions in neuropathological conditions.
2. Neural circuits governing threat processing and inhibitory adaptive learning
2. Neural circuits governing threat processing and inhibitory adaptive learning
The detection of a potential threat triggers an immediate defensive response essential for survival. Abnormal processing of threat-related information, particularly impairments in inhibitory adaptive learning—defined as the ability to reduce threat responses upon repeated exposures in the absence of an aversive stimulus—can lead to behavioral maladaptation in various neuropsychiatric conditions.
A second focus of our research is to identify candidate neuronal circuits that encode different aspects of threat processing, along with the molecular signatures that reflect learning plasticity in response to threat-related information. We also investigate how internal states, such as those altered by pathological stress conditions, influence threat processing and how these responses are shaped by inter-individual genetic variability.
Funding
ACNP Travel Award
Principal Investigator: Susanna Molas
Colorado Clinical and Translational Sciences Institute
Principal Investigator: Susanna Molas
NARSAD Young Investigator Grant
Principal Investigator: Susanna Molas
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