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Publications
Check out what the lab has been up to in some recent highlights
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
June 2024
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.
Measuring Motivation Using the Progressive Ratio Task in Adolescent Mice
Emily Cambre, Elena Christenfeld, Arturo Herraez Torres, Sarah Canetta
May 2023
Changes in reward seeking behavior are present in various psychiatric disorders. These disorders with reward-seeking deficits often have a significant neurodevelopmental component, highlighting the importance of studying motivational changes throughout life. A crucial aspect of reward seeking is 'wanting,' which can be studied in humans and rodents using the progressive ratio task. Although prior protocols have focused on studying adult mice, this paper presents a new protocol that adapts this task for use with adolescent mice.
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
December 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. This paper uses mice to 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 later in life.
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
May 2022
Impaired cortical maturation is a postulated mechanism in the etiology of neurodevelopmental disorders, including schizophrenia. In sensory cortex, activity relayed by the thalamus during a postnatal sensitive period is essential for proper cortical maturation. Whether thalamic activity also shapes prefrontal cortical maturation is unknown. This paper establishes that inhibiting thalamic input to the prefrontal cortex during adolsecence, but not adulthood, leads to long-lasting decreases in thalamo-prefrontal projection density, reduced excitatory drive to prefrontal neurons and deficits in prefrontal activity supporting cognitive flexibility.
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
November 2021
While multiple classes of pharmaceutical agents are available to treat symptoms of depression and anxiety, finding the most effective treatment for an individual is currently a process of trial and error. To more precisely understand how disease etiology may predict treatment response, this study looked at whether adult anxiety-like behavior in mice exposed developmentally to the selective serotonin reuptake inhibitor (SSRI) fluoxetine (FLX) might be more effectively treated by chronic administration of FLX or an atypical antidepressant, tianeptine (TIA), in adulthood. The results detailed in the paper demonstrate that TIA may be a promising alternative treatment for patients that fail to respond to typical antidepressants, especially in patients who may have been exposed to changes in early life levels of serotonin, such as in utero exposure to SSRIs.