Dopamine transporter blockade during adolescence increases adult dopamine function, impulsivity, and aggression.

Sensitive developmental periods shape neural circuits and enable adaptation. However, they also engender vulnerability to factors that can perturb developmental trajectories. An understanding of sensitive period phenomena and mechanisms separate from sensory system development is still lacking, yet critical to understanding disease etiology and risk.

5-HT2C receptor blockade reverses SSRI-associated basal ganglia dysfunction and potentiates therapeutic efficacy.

Serotonin (5-HT) selective reuptake inhibitors (SSRIs) are widely used in the treatment of depression and anxiety disorders, but responsiveness is uncertain and side effects often lead to discontinuation. Side effect profiles suggest that SSRIs reduce dopaminergic (DAergic) activity, but specific mechanistic insight is missing. Here we show in mice that SSRIs impair motor function by acting on 5-HT2C receptors in the substantia nigra pars reticulata (SNr), which in turn inhibits nigra pars compacta (SNc) DAergic neurons.

Hippocampal 5-HT Input Regulates Memory Formation and Schaffer Collateral Excitation.

The efficacy and duration of memory storage is regulated by neuromodulatory transmitter actions. While the modulatory transmitter serotonin (5-HT) plays an important role in implicit forms of memory in the invertebrate Aplysia, its function in explicit memory mediated by the mammalian hippocampus is less clear. Specifically, the consequences elicited by the spatio-temporal gradient of endogenous 5-HT release are not known.

New Insights into How Serotonin Selective Reuptake Inhibitors Shape the Developing Brain.

Development passes through sensitive periods, during which plasticity allows for genetic and environmental factors to exert indelible influence on the maturation of the organism. In the context of central nervous system (CNS) development, such sensitive periods shape the formation of neuro-circuits that mediate, regulate, and control behavior. This general mechanism allows for development to be guided by both the genetic blueprint, as well as the environmental context.

Early stress evokes dysregulation of histone modifiers in the medial prefrontal cortex across the life span.

Early stress has been hypothesized to recruit epigenetic mechanisms to mediate persistent molecular, cellular, and behavioral changes. Here, we have examined the consequence of the early life stress of maternal separation (ES) on the gene expression of several histone modifiers that regulate histone acetylation and methylation within the medial prefrontal cortex (mPFC), a key limbic brain region that regulates stress responses and mood-related behavior. ES animals exhibit gene regulation of both writer (histone acetyltransferases and histone methyltransferases) and eraser (histone deacetylases and histone lysine demethylases) classes of histone modifiers.

The adaptive and maladaptive continuum of stress responses - a hippocampal perspective.

Exposure to stressors elicits a spectrum of responses that span from potentially adaptive to maladaptive consequences at the structural, cellular and physiological level. These responses are particularly pronounced in the hippocampus where they also appear to influence hippocampal-dependent cognitive function and emotionality. The factors that influence the nature of stress-evoked consequences include the chronicity, severity, predictability and controllability of the stressors.

Monoamine-sensitive developmental periods impacting adult emotional and cognitive behaviors.

Development passes through sensitive periods, during which plasticity allows for genetic and environmental factors to exert indelible influence on the maturation of the organism. In the context of central nervous system development, such sensitive periods shape the formation of neurocircuits that mediate, regulate, and control behavior. This general mechanism allows for development to be guided by both the genetic blueprint as well as the environmental context.

Early stress prevents the potentiation of muscarinic excitation by calcium release in adult prefrontal cortex.

Background: The experience of early stress contributes to the etiology of several psychiatric disorders and can lead to lasting deficits in working memory and attention. These executive functions require activation of the prefrontal cortex (PFC) by muscarinic M1 acetylcholine (ACh) receptors. Such Gαq-protein coupled receptors trigger the release of calcium (Ca(2+)) from internal stores and elicit prolonged neuronal excitation.

Early stress evokes temporally distinct consequences on the hippocampal transcriptome, anxiety and cognitive behaviour.

The early stress of maternal separation (ES) exerts long-lasting effects on cognition and anxiety. Recent evidence indicates enhanced hippocampus-dependent spatial learning in young adult ES animals, which shifts towards a decline in long-term memory in middle-aged life. Further, we find that ES animals exhibit enhanced anxiety in young adulthood that does not persist into middle-aged life.

Early stress evokes age-dependent biphasic changes in hippocampal neurogenesis, BDNF expression, and cognition.

Background: Adult-onset stressors exert opposing effects on hippocampal neurogenesis and cognition, with enhancement observed following mild stress and dysfunction following severe chronic stress. While early life stress evokes persistent changes in anxiety, it is unknown whether early stress differentially regulates hippocampal neurogenesis, trophic factor expression, and cognition across the life span.

Methods: Hippocampal-dependent cognitive behavior, neurogenesis, and epigenetic regulation of brain-derived neurotrophic factor (Bdnf) expression was examined at distinct time points across the life span in rats subjected to the early stress of maternal separation (ES) and control groups.

Induction of the plasticity-associated immediate early gene Arc by stress and hallucinogens: role of brain-derived neurotrophic factor.

Exposure to stress and hallucinogens in adulthood evokes persistent alterations in neurocircuitry and emotional behaviour. The structural and functional changes induced by stress and hallucinogen exposure are thought to involve transcriptional alterations in specific effector immediate early genes. The immediate early gene, activity regulated cytoskeletal-associated protein (Arc), is important for both activity and experience dependent plasticity.