Prefrontal cortical regulation of brainwide circuit dynamics and reward-related behavior

Science, Год журнала: 2015, Номер 351(6268)

Опубликована: Дек. 31, 2015

Motivation for reward drives adaptive behaviors, whereas impairment of perception and experience (anhedonia) can contribute to psychiatric diseases, including depression schizophrenia. We sought test the hypothesis that medial prefrontal cortex (mPFC) controls interactions among specific subcortical regions govern hedonic responses. By using optogenetic functional magnetic resonance imaging locally manipulate but globally visualize neural activity in rats, we found dopamine neuron stimulation striatal activity, increased mPFC excitability reduces this response inhibits behavioral drive dopaminergic stimulation. This chronic overactivity also stably suppresses natural reward-motivated behaviors induces new brainwide interactions, which predict degree anhedonia individuals. These findings describe a mechanism by modulates expression reward-seeking behavior, regulating dynamical between distant regions.

Язык: Английский

---

Bidirectional Control of Social Hierarchy by Synaptic Efficacy in Medial Prefrontal Cortex

Science, Год журнала: 2011, Номер 334(6056), С. 693 - 697

Опубликована: Сен. 30, 2011

Dominance hierarchy has a profound impact on animals' survival, health, and reproductive success, but its neural circuit mechanism is virtually unknown. We found that dominance ranking in mice transitive, relatively stable, highly correlates among multiple behavior measures. Recording from layer V pyramidal neurons of the medial prefrontal cortex (mPFC) showed higher strength excitatory synaptic inputs with ranking, as compared their subordinate cage mates. Furthermore, molecular manipulations resulted an increase decrease efficacy dorsal mPFC caused upward downward movement social rank, respectively. These results provide direct evidence for mPFC's involvement suggest rank plastic can be tuned by altering cells.

Язык: Английский

---

Neural Mechanisms of Stress Resilience and Vulnerability

Neuron, Год журнала: 2012, Номер 75(5), С. 747 - 761

Опубликована: Сен. 1, 2012

Язык: Английский

---

Ventral hippocampal afferents to the nucleus accumbens regulate susceptibility to depression

Nature Communications, Год журнала: 2015, Номер 6(1)

Опубликована: Май 8, 2015

Abstract Enhanced glutamatergic transmission in the nucleus accumbens (NAc), a region critical for reward and motivation, has been implicated pathophysiology of depression; however, afferent source this increased glutamate tone is not known. The NAc receives inputs from medial prefrontal cortex (mPFC), ventral hippocampus (vHIP) basolateral amygdala (AMY). Here, we demonstrate that vHIP afferents to regulate susceptibility chronic social defeat stress (CSDS). We observe reduced activity mice resilient CSDS. Furthermore, attenuation vHIP-NAc by optogenetic induction long-term depression pro-resilient, whereas acute enhancement input pro-susceptible. This effect specific NAc, as stimulation either mPFC or AMY pro-resilient. These data indicate uniquely CSDS, highlighting an important, novel circuit-specific mechanism depression.

Язык: Английский

---

The ecology of human fear: survival optimization and the nervous system

Frontiers in Neuroscience, Год журнала: 2015, Номер 9

Опубликована: Март 18, 2015

We propose a Survival Optimization System (SOS) to account for the strategies that humans and other animals use defend against recurring novel threats. The SOS attempts merge ecological models define repertoire of contextually relevant threat induced survival behaviors with contemporary approaches human affective science. first goal nervous system is reduce surprise optimize actions by (i) predicting sensory landscape, through simulation possible encounters threat, selecting appropriate action pre-encounter avoidance (ii) prevention in which organism manufactures safe environments. When potential encountered (iii) orienting engaged determine whether ignores stimulus or switches into process (iv) assessment, where monitors stimulus, weighs value, predicts searches safety, guides behavioral crucial directed escape. under imminent attack, (v) defensive systems evoke fast reflexive indirect escape (i.e. fight flight). This cascade responses increasing magnitude are underwritten an interconnected neural architecture extends from cortical hippocampal circuits, attention, including amygdala, striatum, hard-wired midbrain. also includes modulatory feature consisting cognitive appraisal flexibly guide perception, risk action. Moreover, personal vicarious fine-tune via model-based learning, higher organisms bridging data face-to-face predators. Our theory unifies divergent field science, proposing highly integrated, optimized avoid dangers.

Язык: Английский

---

50 years of hurdles and hope in anxiolytic drug discovery

Nature Reviews Drug Discovery, Год журнала: 2013, Номер 12(9), С. 667 - 687

Опубликована: Авг. 30, 2013

Язык: Английский

---

What, If Anything, Is Rodent Prefrontal Cortex?

eNeuro, Год журнала: 2018, Номер 5(5), С. ENEURO.0315 - 18.2018

Опубликована: Сен. 1, 2018

Prefrontal cortex (PFC) means different things to people. In recent years, there has been a major increase in publications on the PFC, especially using mice. However, inconsistencies nomenclature and anatomical boundaries of PFC areas made it difficult for researchers compare data interpret findings across species. We conducted meta-analysis humans rodents found dramatic differences focus research these addition, we compared terms criteria several common rodent brain atlases among, even within, leading atlases. To assess impact issues community, survey established their use little consensus. report results propose an alternative scheme interpreting from studies, based structural analysis corpus callosum used anterior cingulate (ACC) primates.

Язык: Английский

---

Construction of implantable optical fibers for long-term optogenetic manipulation of neural circuits

Nature Protocols, Год журнала: 2011, Номер 7(1), С. 12 - 23

Опубликована: Дек. 8, 2011

Язык: Английский

---

Brain circuit dysfunction in post-traumatic stress disorder: from mouse to man

Nature reviews. Neuroscience, Год журнала: 2018, Номер 19(9), С. 535 - 551

Опубликована: Июль 27, 2018

Язык: Английский

---

Dendritic Spines in Depression: What We Learned from Animal Models

Neural Plasticity, Год журнала: 2016, Номер 2016, С. 1 - 26

Опубликована: Янв. 1, 2016

Depression, a severe psychiatric disorder, has been studied for decades, but the underlying mechanisms still remain largely unknown. Depression is closely associated with alterations in dendritic spine morphology and density. Therefore, understanding spines vital uncovering depression. Several chronic stress models, including restraint (CRS), unpredictable mild (CUMS), social defeat (CSDS), have used to recapitulate depression-like behaviors rodents study mechanisms. In comparison CRS, CUMS overcomes habituation widely model behaviors. CSDS one of most frequently models depression, it limited male mice. Generally, causes atrophy loss neurons hippocampus prefrontal cortex. Meanwhile, amygdala nucleus accumbens exhibit an increase These induced by are often accompanied However, poorly understood. This review summarizes our current stress-induced remodeling hippocampus, cortex, orbitofrontal amygdala, also discusses putative

Язык: Английский

---