Publications
Check out what the lab has been up to in some recent highlights
Measuring Motivation Using the Progressive Ratio Task in Adolescent Mice
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
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
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.
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.