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Impaired cortical maturation is a postulated mechanism in the etiology of neurodevelopmental disorders, including schizophrenia. In the 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. We show that inhibiting the mediodorsal and midline thalamus in mice during adolescence leads to a long-lasting decrease in thalamo–prefrontal projection density and reduced excitatory drive to prefrontal neurons. It also caused prefrontal-dependent cognitive deficits during adulthood associated with disrupted prefrontal cross-correlations and task outcome encoding. Thalamic inhibition during adulthood had no long-lasting consequences. Exciting the thalamus in adulthood during a cognitive task rescued prefrontal cross-correlations, task outcome encoding and cognitive deficits. These data point to adolescence as a sensitive window of thalamocortical circuit maturation. Furthermore, by supporting prefrontal network activity, boosting thalamic activity provides a potential therapeutic strategy for rescuing cognitive deficits in neurodevelopmental disorders. Benoit et al. show that inhibition of the thalamus during adolescence leads to long-lasting changes in prefrontal cortex function and behavior, demonstrating the importance of adolescent thalamic activity for prefrontal circuit maturation.

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.

Olfaction is an important sensory modality driving fundamental behaviors. During odor-dependent learning, a positive value is commonly assigned to an odorant, and multiple forms of plasticity are involved when such odor–reward associations are formed. In rodents, one of the mechanisms underlying plasticity in the olfactory bulb consists in recruiting new neurons daily throughout life. However, it is still unknown whether adult-born neurons might participate in encoding odor value. Here, we demonstrate that exposure to reward-associated odors specifically increases activity of adult-born neurons but not preexisting neurons. Remarkably, adult-born neuron activation during rewarded odor presentation heightens discrimination learning and enhances the ability to update the odor value during reversal association. Moreover, in some cases, activation of this interneuron population can trigger olfactory learning without sensory stimulation. Taken together, our results show a specific involvement of adult-born neurons in facilitating odor–reward association during adaptive learning.

1. Dispersal is a key mechanism enabling species to adjust their geographic range to rapid global change. However, dispersal is costly and environmental modifications are likely to modify the cost–benefit balance of individual dispersal decisions, for example, by decreasing functional connectivity. 2. Dispersal costs occur during departure, transience and settlement, and are levied in terms of energy, risk, time and lost opportunity, potentially influencing individual fitness. However, to the best of our knowledge, no study has yet quantified the energetic costs of dispersal across the dispersal period by comparing dispersing and philopatric individuals in the wild. 3. Here, we employed animal‐borne biologgers on a relatively large sample (N = 105) of juvenile roe deer to estimate energy expenditure indexed using the vector of dynamic body acceleration and mobility (distance travelled) in an intensively monitored population in the south‐west of France. We predicted that energy expenditure would be higher in dispersers compared to philopatric individuals. We expected costs to be (a) particularly high during transience, (b) especially high in the more fragmented areas of the landscape and (c) concentrated during the night to avoid disturbance caused by human activity. 4. There were no differences in energy expenditure between dispersers and philopatric individuals during the pre‐dispersal phase. However, dispersers expended around 22% more energy and travelled around 63% further per day than philopatric individuals during transience. Differences in energy expenditure were much less pronounced during the settlement phase. The costs of transience were almost uniquely confined to the dawn period, when dispersers spent 23% more energy and travelled 112% further than philopatric individuals. Finally, the energetic costs of transience per unit time and the total distance travelled to locate a suitable settlement range were higher in areas of high road density. 5. Our results provide strong support for the hypothesis that natal dispersal is energetically costly and indicate that transience is the most costly part of the process, particularly in fragmented landscapes. Further work is required to link dispersal costs with fitness components so as to understand the likely outcome of further environmental modifications on the evolution of dispersal behaviour.

Summary Sensitive periods in which experience-driven changes in activity persistently shape circuit function are well-described in sensory cortex. Whether comparable periods govern the development of associative cortical areas, like the prefrontal cortex, remains unclear. Here, we focus on the role of activity in the maturation and circuit integration of prefrontal parvalbumin-expressing interneurons, as these cells play an essential role in sensory cortical maturation and develop in lockstep with overall prefrontal circuit function. We found that transiently decreasing prefrontal parvalbumin activity during peripubertal and adolescent development results in persistent impairments in adult functional connectivity, in vivo network function and set-shifting behavior that can be rescued by targeted activation of these interneurons in the adult animal. In contrast, comparable adult inhibition had no lasting effects. These findings identify an activity-dependent sensitive period for prefrontal parvalbumin maturation and highlight how abnormal parvalbumin activity early in life can persistently alter adult circuit function and behavior. Competing Interest Statement The authors have declared no competing interest. Footnotes * ↵6 Lead contact; Further information and requests for resources and reagents should be directed to and will be fulfilled by the lead contact, Sarah E. Canetta (ses2119{at}cumc.columbia.edu) * ↵7 Senior author

Cognitive impairments are a hallmark of many, if not all, psychiatric disorders. They include deficits in working memory, attention, and cognitive flexibility. The prefrontal cortex (PFC) is essential for these cognitive functions and has been implicated in psychiatric disorders, including schizophrenia. The PFC receives reciprocal inputs from the thalamus, and this thalamo-PFC circuitry supports cognition. In patients with schizophrenia, who have impaired cognitive functioning, thalamo-PFC connectivity is disrupted. This finding is also seen in adolescents at high risk for the disorder, even before diagnosis.While impaired cortical maturation has been postulated as a mechanism in the etiology of schizophrenia, the postnatal development of thalamo-PFC circuitry is still poorly understood. In sensory cortex, activity relayed by the thalamus during a postnatal sensitive period is essential for proper cortical maturation. However, whether thalamic activity also shapes maturation of the PFC is unknown.Here, I will present evidence to support the hypothesis that adolescence represents a sensitive period, during which the PFC is susceptible to transient perturbations in thalamic input activity, resulting in persistent changes in circuitry.In Chapter 1, I present the existing literature on schizophrenia and our current understanding of its etiology. I then review the structure and connectivity of the PFC and its inputs, including the thalamus, in the context of schizophrenia and cognition. Next, I discuss the role of adolescence in the development of these structures and circuits. Finally, I introduce the concept of sensitive periods and outline the hypothesis that a similar process may occur in the context of the adolescent development of thalamo-PFC circuitry.To assess cognitive functioning in mouse models, I developed an operant-based working memory task. In Chapter 2, I describe this newly developed task and demonstrate that behavioral performance in the task is susceptible to PFC lesions. Thus, the task offers a new approach to studying PFC cognitive function.In Chapter 3, I discuss work done to address the hypothesis of adolescence as a sensitive period in the development of thalamo-PFC circuitry. I established an approach whereby I can transiently reduce activity in the thalamus during specific time windows. In this way, I compared the persistent effects of transient thalamic inhibition during adolescence and adulthood. I found that adolescent thalamic inhibition causes long-lasting deficits in cognitive behavioral performance, including the operant-based working memory task described in Chapter 2 and a cognitive flexibility task, decreased PFC cellular excitability, and reduced thalamo-PFC projection density. Meanwhile, adult thalamic inhibition has no persistent consequences on behavior or PFC excitability.Adolescent thalamic inhibition also results in disrupted PFC cellular cross-correlations and task outcome encoding during the cognitive flexibility task. Strikingly, exciting the thalamus in adulthood during the behavioral task rescues PFC cross-correlations, task outcome encoding, and the cognitive deficit. These data support the hypothesis that adolescence is a sensitive period in thalamo-PFC circuit maturation as adolescent thalamic inhibition has long-lasting consequences on PFC circuitry, while adult thalamic inhibition has no persistent effects. Moreover, these results highlight the role of the thalamus as a non-specific facilitator of PFC activity, expanding our understanding of this thalamic function to additional cognitive contexts. By supporting PFC network activity, boosting thalamic activity provides a potential therapeutic strategy for rescuing cognitive deficits in neurodevelopmental disorders.Finally, in Chapter 4, I conclude with a general discussion. I highlight major take-aways from this work as well as next steps in our exploration of these crucial neural circuits. Together, the findings outlined here offer new promise for early diagnosis and treatment options for patients with cognitive impairments and psychiatric disorders.

Deficits in working memory, which includes both the ability to learn and to retain information short-term, are a hallmark of many cognitive disorders. Our study analyzes data from a neuroscience experiment on animal subjects, where performance on a working memory task was recorded as repeated binary success or failure data. We estimate continuous probability of success curves from this binary data in the context of functional data analysis, which is largely used in biological processes that are intrinsically continuous. We then register these curves to decompose each function into its amplitude, representing overall performance, and its phase, representing the speed of learning or response. Because we are able to separate speed from performance, we can address the crucial question of whether a cognitive disorder impacts not only how well subjects can learn and remember, but also how fast. This allows us to analyze the components jointly to uncover how speed and performance co-vary, and to compare them separately to pinpoint whether group differences stem from a deficit in peak performance or a change in speed.

The coronavirus disease 2019 (COVID-19) pandemic presents an unprecedented challenge to public health, with over 233 million confirmed cases and over 4.6 million deaths globally as of September 2021 . Although many studies have reported worse mental health outcomes during the early weeks of the pandemic, some sources suggest a gradual decrease in anxiety and depressive symptoms during the lockdown . It remains to be explained whether mental health continued to deteriorate during the initial lockdown or whether there were signs of stabilization or improvement in the mental health of community-dwelling middle-aged and older adults. Our results showed that adults had twice the odds of depressive symptoms during the pandemic compared with the prepandemic period, with subgroups characterized by lower socioeconomic status and poor health-related factors experiencing a greater impact. Over 43% of adults showed a pattern of moderate or clinically high levels of depressive symptoms at baseline that increased over time. Loneliness and COVID-19 stressors were predictors of worsening depressive symptom trajectories. The disparities and patterns in the depressive symptom trajectories suggest that the negative mental health impacts of the pandemic persist and may worsen over time. Interventions that address the pandemic stressors and alleviate their impact on the mental health of adults are needed.

The behavioural trade-off between foraging and risk avoidance is expected to be particularly acute during gestation and lactation, when the energetic demands of reproduction peak. We investigated how female roe deer, an income breeding ungulate, adjust their management of this trade-off during the birth period in terms of foraging activity and habitat use. We showed that activity levels of reproductive females more than doubled immediately following parturition, when energy demand is highest. Moreover, reproductive females increased their use of open habitat during daytime and ranged closer to roads, but slightly further from refuge woodland, compared to non-reproductive females. However, these post-partum modifications in behaviour were particularly pronounced in late-parturient females who adopted a more risk prone tactic, presumably to compensate for the fitness handicap of their late-born offspring. In income breeders, individuals that give birth late may be forced to trade risk avoidance for resource acquisition during peak allocation to reproduction, likely with significant fitness consequences.

I belonged to a local service club who rents a booth every year at the Harrow Fair. This is a charitable organization that sells tickets on a car to raise money for the community. My partner and I have worked at the fair many years with no problems. This year, on the Friday morning with club shirts on and chairs in hand, we were told we had to pay $15 each for a pass. We explained we were just working for three hours for our club, and there should be a pass for us at the office. There was no pass, and they demanded we pay.