RESEARCH
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Background
Background
Novelty responses are fundamental mechanisms that enable organisms to adapt to changes in dynamic environments. The behavioral and neural signatures of novelty processing are not static; they are shaped by familiarity, as organisms learn to update the significance of environmental stimuli with experience. Understanding these processes is essential for elucidating experience-based adaptive behavior and how disruptions in novelty processing may contribute to neurological disorders.
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 across distinct sensory stimuli; 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 adaptive learning
2. Neural circuits governing threat processing and 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.
Building on recent work (Williams et al., Mol. Psychiatry, 2025) a second focus of our research is to identify 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.
Our Research is Multidisciplinary and Integrates Advanced Systems Neuroscience Approaches
Behavioral Annotation
We use supervised and unsupervised machine learning models for multi-pose animal estimation and behavioral classification.
Imaging Tools
We combine in vivo multi-site fiber photometry recordings and single-cell imaging time locked to behavioral events.
Neuronal Ensemble Tagging
We have established mouse models and genetic tools for neuronal ensemble tagging with effector genes, enabling the analysis of regional activation patterns through whole brain imaging.
Molecular Biology
We combine in situ RNA Scope, immunofluorescence and single cell spatial transcriptomics techniques to elucidate gene transcription patterns in selected neuronal populations.
Circuit Mapping
Through viral-mediated anterograde and retrograde tracing we define neuronal circuitry of selectively identified genetic populations.
Activity Manipulations
We use time-locked optogenetics and chemogenetics tools (DREADDs) to manipulate activity of genetically identified circuits to establish their role in behavioral domains. Combining real-time time-locked optogenetics with neural activity recordings in freely-moving animals we determine the neural signatures driving these effects.
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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