Sarah Canetta

Verified @cumc.columbia.edu

Assistant Professor, Department of Psychiatry
Columbia University Medical Center

Sarah Canetta


         Download Compact PDF  
https://researchid.co/scanetta

RESEARCH, TEACHING, or OTHER INTERESTS

Neuroscience
22

Scopus Publications

Scopus Publications

  • Chronic administration of methocinnamox, a mu-opioid receptor antagonist, reduces hedonic response without impacting motivation in mice
    Misbah Sheikh, Emily Cambre, Cory Langreck, Jonathan A. Javitch, Sarah E. Canetta
    Psychopharmacology, 2025
  • Peripuberty Is a Sensitive Period for Prefrontal Parvalbumin Interneuron Activity to Impact Adult Cognitive Flexibility
    Gabriella M. Sahyoun, Trang Dao Do, Amanda Anqueira-Gonzàlez, Ava Hornblass, Sarah E. Canetta
    Developmental Neuroscience, 2025
    <b><i>Introduction:</i></b> Developmental windows in which experiences can elicit long-lasting effects on brain circuitry and behavior are called “sensitive periods” and reflect a state of heightened plasticity. The classic example of a sensitive period comes from studies of sensory systems, like the visual system, where early visual experience is required for normal wiring of primary visual cortex and proper visual functioning. At a mechanistic level, loss of incoming visual input results in a decrease in activity in thalamocortical neurons representing the affected eye, resulting in an activity-dependent reduction in the representation of those inputs in the visual cortex and loss of visual perception in that eye. While associative cortical regions like the medial prefrontal cortex (mPFC) do not receive direct sensory input, recent findings demonstrate that changes in activity levels experienced by this region during defined windows in early development may also result in long-lasting changes in prefrontal cortical circuitry, network function, and behavior. For example, we recently demonstrated that decreasing the activity of mPFC parvalbumin-expressing (PV) interneurons during a period of time encompassing peripuberty (postnatal day P14) to adolescence (P50) led to a long-lasting decrease in their functional inhibition of pyramidal cells, as well as impairments in cognitive flexibility. While the effects of manipulating mPFC PV interneuron activity were selective to development, and not adulthood, the exact timing of the sensitive period for this manipulation remains unknown. <b><i>Methods:</i></b> To refine the sensitive period in which inhibiting mPFC PV cell activity can lead to persistent effects on prefrontal functioning, we used a chemogenetic approach to restrict our inhibition of mPFC PV activity to two distinct windows: (1) peripuberty (P14–P32) and (2) early adolescence (P33–P50). We then investigated adult behavior after P90. In parallel, we performed histological analysis of molecular markers associated with sensitive period onset and offset in visual cortex, to define the onset and offset of peak-sensitive period plasticity in the mPFC. <b><i>Results:</i></b> We found that inhibition of mPFC PV interneurons in peripuberty (P14–P32), but not adolescence (P33–P50), led to an impairment in set-shifting behavior in adulthood manifest as an increase in trials to reach criterion performance and errors. Consistent with a pubertal onset of sensitive period plasticity in the PFC, we found that histological markers of sensitive period onset and offset also demarcated P14 and P35, respectively. The time course of expression of these markers was similar in visual cortex. <b><i>Conclusion:</i></b> Both lines of research converge on the peripubertal period (P14–P32) as one of heightened sensitive period plasticity in the mPFC. Further, our direct comparison of markers of sensitive period plasticity across the prefrontal and visual cortex suggests a similar time course of expression, challenging the notion that sensitive periods occur hierarchically. Together, these findings extend our knowledge about the nature and timing of sensitive period plasticity in the developing mPFC.
  • Adolescent Thalamoprefrontal Inhibition Leads to Changes in Intrinsic Prefrontal Network Connectivity
    David Petersen, Ricardo Raudales, Ariadna Kim Silva, Christoph Kellendonk, Sarah Canetta
    Eneuro, 2024
    Adolescent inhibition of thalamocortical projections from postnatal days P20 to 50 leads to long-lasting deficits in prefrontal cortex function and cognition in the adult mouse. While this suggests a role of thalamic activity in prefrontal cortex maturation, it is unclear how inhibition of these projections affects prefrontal circuitry during adolescence. Here, we used chemogenetic tools to inhibit thalamoprefrontal projections in male/female mice from P20 to P35 and measured synaptic inputs to prefrontal pyramidal neurons by layer (either II/III or V/VI) and projection target (mediodorsal thalamus (MD), nucleus accumbens (NAc), or callosal prefrontal projections) 24 h later using slice physiology. We found a decrease in the frequency of excitatory and inhibitory currents in layer II/III NAc and layer V/VI MD-projecting neurons while layer V/VI NAc-projecting neurons showed an increase in the amplitude of excitatory and inhibitory currents. Regarding cortical projections, the frequency of inhibitory but not excitatory currents was enhanced in contralateral mPFC-projecting neurons. Notably, despite these complex changes in individual levels of excitation and inhibition, the overall balance between excitation and inhibition in each cell was only altered in the contralateral mPFC projections. This finding suggests homeostatic regulation occurs within subcortically but not intracortical callosal-projecting neurons. Increased inhibition of intraprefrontal connectivity may therefore be particularly important for prefrontal cortex circuit maturation. Finally, we observed cognitive deficits in the adult mouse using this narrowed window of thalamocortical inhibition.
  • Measuring Motivation Using the Progressive Ratio Task in Adolescent Mice
    Emily Cambre, Elena Christenfeld, Arturo Herraez Torres, Sarah Canetta
    Current Protocols, 2023
    Alterations in reward seeking are a hallmark of multiple psychiatric disorders, including substance abuse and depression. One important aspect of reward seeking is ‘wanting’, which can be operationalized in both humans and rodents in tasks such as the progressive ratio, in which an increasing amount of work is required to earn a given reward. Importantly, many disorders with reward‐seeking deficits are believed to have an important neurodevelopmental component, underscoring the importance of being able to study changes in motivation across the lifespan. Although this task has been adapted for both adult and adolescent rats, in mice it has predominantly been used to assay motivational changes in adults. Specific concerns in adapting this task from adult to adolescent mice include (1) optimizing a food restriction paradigm suitable for growing animals whose weights are naturally dynamically changing and (2) identifying task conditions that allow younger, smaller mice to perform the task while minimizing the length of the behavioral shaping required to measure motivation at specific developmental dates. Toward that end, we now report a protocol for appropriate weight management in developing animals that require food restriction, and a protocol for behavioral shaping and progressive ratio testing in adolescent mice, including an assessment of whether the animals perform better with lever presses or nose pokes as the required operant response. © 2023 Wiley Periodicals LLC.Basic Protocol 1: Food restriction and weight management in the context of developing miceAlternate Protocol: Food restriction and weight management of developing mice without projected growth chart: Utilization of baseline miceBasic Protocol 2: Operant box design, progressive ratio training, testing, and data analysis in adolescent mice
  • Thalamocortical Development: A Neurodevelopmental Framework for Schizophrenia
    Laura J. Benoit, Sarah Canetta, Christoph Kellendonk
    Biological Psychiatry, 2022
  • Adolescent thalamic inhibition leads to long-lasting impairments in prefrontal cortex function
    Laura J. Benoit, Emma S. Holt, Lorenzo Posani, Stefano Fusi, Alexander Z. Harris, Sarah Canetta, Christoph Kellendonk
    Nature Neuroscience, 2022
  • Mature parvalbumin interneuron function in prefrontal cortex requires activity during a postnatal sensitive period
    Sarah E Canetta, Emma S Holt, Laura J Benoit, Eric Teboul, Gabriella M Sahyoun, R Todd Ogden, Alexander Z Harris, Christoph Kellendonk
    Elife, 2022
    In their seminal findings, Hubel and Wiesel identified sensitive periods in which experience can exert lasting effects on adult visual cortical functioning and behavior via transient changes in neuronal activity during development. Whether comparable sensitive periods exist for non-sensory cortices, such as the prefrontal cortex, in which alterations in activity determine adult circuit function and behavior is still an active area of research. Here, using mice we demonstrate that inhibition of prefrontal parvalbumin (PV)-expressing interneurons during the juvenile and adolescent period, results in persistent impairments in adult prefrontal circuit connectivity, in vivo network function, and behavioral flexibility that can be reversed by targeted activation of PV interneurons in adulthood. In contrast, reversible suppression of PV interneuron activity in adulthood produces no lasting effects. These findings identify an activity-dependent sensitive period for prefrontal circuit maturation and highlight how abnormal PV interneuron activity during development alters adult prefrontal circuit function and cognitive behavior.
  • Tianeptine, but not fluoxetine, decreases avoidant behavior in a mouse model of early developmental exposure to fluoxetine
    Elizabeth A. Pekarskaya, Emma S. Holt, Jay A. Gingrich, Mark S. Ansorge, Jonathan A. Javitch, Sarah E. Canetta
    Scientific Reports, 2021
    Depression and anxiety, two of the most common mental health disorders, share common symptoms and treatments. Most pharmacological agents available to treat these disorders target monoamine systems. Currently, finding the most effective treatment for an individual is a process of trial and error. To better understand how disease etiology may predict treatment response, we studied mice exposed developmentally to the selective serotonin reuptake inhibitor (SSRI) fluoxetine (FLX). These mice show the murine equivalent of anxiety- and depression-like symptoms in adulthood and here we report that these mice are also behaviorally resistant to the antidepressant-like effects of adult SSRI administration. We investigated whether tianeptine (TIA), which exerts its therapeutic effects through agonism of the mu-opioid receptor instead of targeting monoaminergic systems, would be more effective in this model. We found that C57BL/6J pups exposed to FLX from postnatal day 2 to 11 (PNFLX, the mouse equivalent in terms of brain development to the human third trimester) showed increased avoidant behaviors as adults that failed to improve, or were even exacerbated, by chronic SSRI treatment. By contrast, avoidant behaviors in these same mice were drastically improved following chronic treatment with TIA. Overall, this demonstrates that TIA may be a promising alternative treatment for patients that fail to respond to typical antidepressants, especially in patients whose serotonergic system has been altered by in utero exposure to SSRIs.
  • Medial Prefrontal Lesions Impair Performance in an Operant Delayed Nonmatch to Sample Working Memory Task
    Laura J. Benoit, Emma S. Holt, Eric Teboul, Joshua P. Taliaferro, Christoph Kellendonk, Sarah Canetta
    Behavioral Neuroscience, 2020
    Cognitive functions, such as working memory, are disrupted in most psychiatric disorders. Many of these processes are believed to depend on the medial prefrontal cortex (mPFC). Traditionally, maze-based behavioral tasks, which have a strong exploratory component, have been used to study the role of the mPFC in working memory in mice. In maze tasks, mice navigate through the environment and require a significant amount of time to complete each trial, thereby limiting the number of trials that can be run per day. Here, we show that an operant-based delayed nonmatch to sample (DNMS) working memory task, with shorter trial lengths and a smaller exploratory component, is also mPFC-dependent. We created excitotoxic lesions in the mPFC of mice and found impairments in both the acquisition of the task, with no delay, and in the performance with delays introduced. Importantly, we saw no differences in trial length, reward collection, or lever-press latencies, indicating that the difference in performance was not due to a change in motivation or mobility. Using this operant DNMS task will facilitate the analysis of working memory and improve our understanding of the physiology and circuit mechanisms underlying this cognitive process. (PsycInfo Database Record (c) 2020 APA, all rights reserved).
  • Hippocampal-Prefrontal Theta Transmission Regulates Avoidance Behavior
    Nancy Padilla-Coreano, Sarah Canetta, Rachel M. Mikofsky, Emily Alway, Johannes Passecker, Maxym V. Myroshnychenko, Alvaro L. Garcia-Garcia, Richard Warren, Eric Teboul, Dakota R. Blackman, Mitchell P. Morton, Sofiya Hupalo, Kay M. Tye, Christoph Kellendonk, David A. Kupferschmidt, Joshua A. Gordon
    Neuron, 2019
  • When Time Matters: An Adolescent Intervention to Prevent Adult Brain Dysfunction
    Sarah Canetta, Christoph Kellendonk
    Cell, 2019
  • Serotonin inputs to the dorsal BNST modulate anxiety in a 5-HT1A receptor-dependent manner
    A L Garcia-Garcia, S Canetta, J M Stujenske, N S Burghardt, M S Ansorge, A Dranovsky, E D Leonardo
    Molecular Psychiatry, 2018
  • Can we use mice to study schizophrenia?
    Sarah Canetta, Christoph Kellendonk
    Philosophical Transactions of the Royal Society B Biological Sciences, 2018
  • Serotonin Signaling through Prefrontal Cortex 5-HT1A Receptors during Adolescence Can Determine Baseline Mood-Related Behaviors
    Alvaro L. Garcia-Garcia, Qingyuan Meng, Sarah Canetta, Alain M. Gardier, Bruno P. Guiard, Christoph Kellendonk, Alex Dranovsky, E. David Leonardo
    Cell Reports, 2017
  • Maternal immune activation leads to selective functional deficits in offspring parvalbumin interneurons
    S Canetta, S Bolkan, N Padilla-Coreano, L J Song, R Sahn, N L Harrison, J A Gordon, A Brown, C Kellendonk
    Molecular Psychiatry, 2016
  • Maternal immune activation does not alter the number of perisomatic parvalbumin-positive boutons in the offspring prefrontal cortex
    S Canetta, S Bolkan, N Padilla-Coreano, L J Song, R Sahn, N L Harrison, J A Gordon, A Brown, C Kellendonk
    Molecular Psychiatry, 2016
  • Response to Selten and van Os
    Sarah Canetta, Alan S. Brown
    American Journal of Psychiatry, 2015
  • Elevated maternal C-reactive protein and increased risk of schizophrenia in a national birth cohort
    Sarah Canetta, Andre Sourander, Heljä-Marja Surcel, Susanna Hinkka-Yli-Salomäki, Jaana Leiviskä, Christoph Kellendonk, Ian W. McKeague, Alan S. Brown
    American Journal of Psychiatry, 2014
  • Serological documentation of maternal influenza exposure and bipolar disorder in adult offspring
    Sarah E. Canetta, Yuanyuan Bao, Mary Dawn T. Co, Francis A. Ennis, John Cruz, Masanori Terajima, Ling Shen, Christoph Kellendonk, Catherine A. Schaefer, Alan S. Brown
    American Journal of Psychiatry, 2014
  • Prenatal infection, maternal immune activation, and risk for schizophrenia
    Sarah Canetta, Alan Brown
    Translational Neuroscience, 2012
  • Type III Nrg1 back signaling enhances functional TRPV1 along sensory axons contributing to basal and inflammatory thermal pain sensation
    Sarah E. Canetta, Edlira Luca, Elyse Pertot, Lorna W. Role, David A. Talmage
    Plos One, 2011
  • Presynaptic type III neuregulin1-ErbB signaling targets α 7 nicotinic acetylcholine receptors to axons
    Melissa L. Hancock, Sarah E. Canetta, Lorna W. Role, David A. Talmage
    Journal of Cell Biology, 2008