Neurobiology of Stress最新文献

Exposure to chronic stress contributes considerably to the development of cognitive impairments in psychiatric disorders such as depression, generalized anxiety disorder (GAD), obsessive-compulsive disorder (OCD), post-traumatic stress disorder (PTSD), and addictive behavior. Unfortunately, unlike mood-related symptoms, cognitive impairments are not effectively treated by available therapies, a situation in part resulting from a still incomplete knowledge of the neurobiological substrates that underly cognitive domains and the difficulty in generating interventions that are both efficacious and safe.

In this review, we will present an overview of the cognitive domains affected by stress with a specific focus on cognitive flexibility, behavioral inhibition, and working memory. We will then consider the effects of stress on neuronal correlates of cognitive function and the factors which may modulate the interaction of stress and cognition. Finally, we will discuss intervention strategies for treatment of stress-related disorders and gaps in knowledge with emerging new treatments under development.

Understanding how cognitive impairment occurs during exposure to chronic stress is crucial to make progress towards the development of new and effective therapeutic approaches.

Adverse early life experiences are strongly associated with reduced cognitive function throughout life. The link is strong in many human studies, but these do not enable assigning causality, and the limited access to the live human brain can impede establishing the mechanisms by which early-life adversity (ELA) may induce cognitive problems. In experimental models, artificially imposed chronic ELA/stress results in deficits in hippocampus dependent memory as well as increased vulnerability to the deleterious effects of adult stress on memory. This causal relation of ELA and life-long memory impairments provides a framework to probe the mechanisms by which ELA may lead to human cognitive problems. Here we focus on the consequences of a one-week exposure to adversity during early postnatal life in the rodent, the spectrum of the ensuing memory deficits, and the mechanisms responsible. We highlight molecular, cellular and circuit mechanisms using convergent trans-disciplinary approaches aiming to enable translation of the discoveries in experimental models to the clinic.

The lateral preoptic area (LPO) is a component of the hypothalamus involved in various physiological functions including sleep-wakefulness transition, thermoregulation, and water-salt balance. In this study, we discovered that distinct LPO excitatory neurons project separately to the aversive processing center lateral habenula (LHb) and the reward processing hub ventral tegmental area (VTA). Following chronic restraint stress (CRS), the LHb-projecting and VTA-projecting LPO neurons exhibited increased and decreased neuronal activities, respectively. Optogenetic activation of LHb-projecting LPO excitatory neurons and LPO excitatory neuronal terminals within LHb evoked aversion and avoidance behaviors, while activation of VTA-projecting LPO excitatory neurons and LPO excitatory neuronal terminals within VTA produced preference and exploratory behaviors in mice. Furthermore, either optogenetic inhibition of LHb-projecting LPO excitatory neurons or activation of VTA-projecting LPO excitatory neurons during CRS effectively prevented the development of depressive-like behaviors. Our study unveils, for the first-time, divergent pathways originating from LPO that regulate opposite affective states in mice and implicates that an imbalance of their activities could lead to depressive-like behaviors. These circuitries represent promising therapeutic targets to relieve emotional dysfunctions in neuropsychiatric disorders.