Oxytocin-dependent reopening of a social reward learning critical period with MDMA

Nardou, Romain; Lewis, Eastman M.; Rothhaas, Rebecca; Xu, Ran; Yang, Aimei; Boyden, Edward S.; Dölen, Gül

doi:10.1038/s41586-019-1075-9

Cited by 225 publications

(240 citation statements)

References 39 publications

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“…Is learning and adaptation during critical periods truly passive as previously thought? While it would be highly advantageous that basic sensory functions do not require more than simple exposure to environmental stimuli for functional maturation, complex skills, cognitive functions and behaviors likely require the involvement of higher brain regions and/or of neuromodulatory systems (Puzerey et al, 2018;Nardou et al, 2019). Future studies are bound to address this in more detail, as well as whether coordination of thalamic and local circuits represents a way to time cortical critical period closure (Toyoizumi et al, 2013;Gu and Cang, 2016).…”

Section: Plasticity In the Developing Cortexmentioning

confidence: 99%

Stability in the Face of Change: Lifelong Experience-Dependent Plasticity in the Sensory Cortex

Ribic

2020

Front. Cell. Neurosci.

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Plasticity is a fundamental property of the nervous system that enables its adaptations to the ever-changing environment. Heightened plasticity typical for developing circuits facilitates their robust experience-dependent functional maturation. This plasticity wanes during adolescence to permit the stabilization of mature brain function, but abundant evidence supports that adult circuits exhibit both transient and long-term experienceinduced plasticity. Cortical plasticity has been extensively studied throughout the life span in sensory systems and the main distinction between development and adulthood arising from these studies is the concept that passive exposure to relevant information is sufficient to drive robust plasticity early in life, while higher-order attentional mechanisms are necessary to drive plastic changes in adults. Recent work in the primary visual and auditory cortices began to define the circuit mechanisms that govern these processes and enable continuous adaptation to the environment, with transient circuit disinhibition emerging as a common prerequisite for both developmental and adult plasticity. Drawing from studies in visual and auditory systems, this review article summarizes recent reports on the circuit and cellular mechanisms of experience-driven plasticity in the developing and adult brains and emphasizes the similarities and differences between them. The benefits of distinct plasticity mechanisms used at different ages are discussed in the context of sensory learning, as well as their relationship to maladaptive plasticity and neurodevelopmental brain disorders. Knowledge gaps and avenues for future work are highlighted, and these will hopefully motivate future research in these areas, particularly those about the learning of complex skills during development.

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Section: Plasticity In the Developing Cortexmentioning

confidence: 99%

Stability in the Face of Change: Lifelong Experience-Dependent Plasticity in the Sensory Cortex

Ribic

2020

Front. Cell. Neurosci.

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“…Moreover, we have recently found that the combination of behavioral therapy (re-socialization in isolated animals) after chronic Fluoxetine treatment, increases the strength of the projection from the vHC to the mPFC and reduces abnormal aggressive behavior in a long-time manner (Mikics et al, 2018). Interestingly, other substances whose efficiency as antidepressants is undergoing a revision both in the context of clinical treatment as well as basic research, such as MDMA (Nardou et al, 2019), ketamine (Berman et al, FIGURE 2 | Diagram showing two different neurodevelopmental trajectories according to its prefrontocortical inputs: (1) an amygdaloid-dominant scenario, with strong projections from the basolateral amygdala to the mPFC, with increased volume in the amygdala which, as discussed in the main text, is related to increased fear expression and neuropsychiatric disorders; and (2) a hippocampal-dominated network, associated to antidepressant action and increased neuroplasticity. We also indicate the possibility of new treatments able to revert the network configuration as explained in the main text.…”

Section: A Critical Period Of Opportunitymentioning

confidence: 99%

“…2000; Li et al, 2010) or isoflurane (Antila et al, 2017), have been shown to reopen a critical period for social behavior through different molecular mechanisms of plasticity, including oxytocin, mTOR and TrkB (Li et al, 2010;Antila et al, 2017;Nardou et al, 2019).…”

Section: A Critical Period Of Opportunitymentioning

confidence: 99%

A Critical Period for Prefrontal Network Configurations Underlying Psychiatric Disorders and Addiction

Guirado

Pérez-Rando

Ferragud

et al. 2020

Front. Behav. Neurosci.

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The medial prefrontal cortex (mPFC) has been classically defined as the brain region responsible for higher cognitive functions, including the decision-making process. Ample information has been gathered during the last 40 years in an attempt to understand how it works. We now know extensively about the connectivity of this region and its relationship with neuromodulatory ascending projection areas, such as the dorsal raphe nucleus (DRN) or the ventral tegmental area (VTA). Both areas are well-known regulators of the reward-based decision-making process and hence likely to be involved in processes like evidence integration, impulsivity or addiction biology, but also in helping us to predict the valence of our future actions: i.e., what is "good" and what is "bad." Here we propose a hypothesis of a critical period, during which the inputs of the mPFC compete for target innervation, establishing specific prefrontal network configurations in the adult brain. We discuss how these different prefrontal configurations are linked to brain diseases such as addiction or neuropsychiatric disorders, and especially how drug abuse and other events during early life stages might lead to the formation of more vulnerable prefrontal network configurations. Finally, we show different promising pharmacological approaches that, when combined with the appropriate stimuli, will be able to re-establish these functional prefrontocortical configurations during adulthood.

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“…Additionally, it is possible that more than one pairing in each social context may be necessary for social CPP. We based our social CPP design on previously published papers 27,92,93 . For instance, using a similar design, Nardou et al 93 reported robust social conditioning in mice which required no additional social pairings.…”

Section: Discussionmentioning

confidence: 99%

Sex differences in adult mood and in stress-induced transcriptional coherence across mesocorticolimbic circuitry

et al. 2020

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Women are approximately two times as likely to be diagnosed with major depressive disorder (MDD) compared to men. While sex differences in MDD might be driven by circulating gonadal hormones, we hypothesized that developmental hormone exposure and/or genetic sex might play a role. Mice were gonadectomized in adulthood to isolate the role of developmental hormones. We examined the effects of developmental gonadal and genetic sex on anhedonia-/depressive-like behaviors under non-stress and chronic stress conditions and performed RNA-sequencing in three mood-relevant brain regions. We used an integrative network approach to identify transcriptional modules and stress-specific hub genes regulating stress susceptibility, with a focus on whether these differed by sex. After identifying sex differences in anhedonia-/depressive-like behaviors (female > male), we show that both developmental hormone exposure (gonadal female > gonadal male) and genetic sex (XX > XY) contribute to the sex difference. The top biological pathways represented by differentially expressed genes were related to immune function; we identify which differentially expressed genes are driven by developmental gonadal or genetic sex. There was very little overlap in genes affected by chronic stress in males and females. We also identified highly co-expressed gene modules affected by stress, some of which were affected in opposite directions in males and females. Since all mice had equivalent hormone exposure in adulthood, these results suggest that sex differences in gonadal hormone exposure during sensitive developmental periods program adult sex differences in mood, and that these sex differences are independent of adult circulating gonadal hormones.

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Oxytocin-dependent reopening of a social reward learning critical period with MDMA

Cited by 225 publications

References 39 publications

Stability in the Face of Change: Lifelong Experience-Dependent Plasticity in the Sensory Cortex

Stability in the Face of Change: Lifelong Experience-Dependent Plasticity in the Sensory Cortex

A Critical Period for Prefrontal Network Configurations Underlying Psychiatric Disorders and Addiction

Sex differences in adult mood and in stress-induced transcriptional coherence across mesocorticolimbic circuitry

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