Covert capture and attenuation of a hippocampus-dependent fear memory

Nature Neuroscience, Год журнала: 2021, Номер 24(5), С. 677 - 684

Опубликована: Апрель 1, 2021

Язык: Английский

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Prefrontal modulation of anxiety through a lens of noradrenergic signaling

Frontiers in Systems Neuroscience, Год журнала: 2023, Номер 17

Опубликована: Апрель 17, 2023

Anxiety disorders are the most common class of mental illness in U.S., affecting 40 million individuals annually. is an adaptive response to a stressful or unpredictable life event. Though evolutionarily thought aid survival, excess intensity duration anxiogenic can lead plethora adverse symptoms and cognitive dysfunction. A wealth data has implicated medial prefrontal cortex (mPFC) regulation anxiety. Norepinephrine (NE) crucial neuromodulator arousal vigilance believed be responsible for many anxiety disorders. NE synthesized locus coeruleus (LC), which sends major noradrenergic inputs mPFC. Given unique properties LC-mPFC connections heterogeneous subpopulation neurons known involved regulating anxiety-like behaviors, likely modulates PFC function cell-type circuit-specific manner. In working memory stress response, follows inverted-U model, where overly high low release associated with sub-optimal neural functioning. contrast, based on current literature review individual contributions disorders, we propose model level- adrenergic receptor-dependent, NE-PFC modulation Further, advent new techniques measure unprecedented spatial temporal resolution will significantly help us understand how

Язык: Английский

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The central amygdala recruits mesocorticolimbic circuitry for pursuit of reward or pain

Nature Communications, Год журнала: 2020, Номер 11(1)

Опубликована: Июнь 1, 2020

Abstract How do brain mechanisms create maladaptive attractions? Here intense attractions are created in laboratory rats by pairing optogenetic channelrhodopsin (ChR2) stimulation of central nucleus amygdala (CeA) with encountering either sucrose, cocaine, or a painful shock-delivering object. We find that pairings make the respective pursue sucrose exclusively, cocaine repeatedly self-inflict shocks. CeA-induced attractions, even to shock-rod, recruit mesocorticolimbic incentive-related circuitry. Shock-associated cues also gain positive incentive value and pursued. Yet motivational effects paired CeA can be reversed negative valence Pavlovian fear learning situation, where ChR2 increases defensive reactions. Finally, switched neutral innocuous stimuli. These results reveal plasticity multiple modes for motivation via circuitry under control activation.

Язык: Английский

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Chronic Stress Induces Maladaptive Behaviors by Activating Corticotropin-Releasing Hormone Signaling in the Mouse Oval Bed Nucleus of the Stria Terminalis

Journal of Neuroscience, Год журнала: 2020, Номер 40(12), С. 2519 - 2537

Опубликована: Фев. 13, 2020

The bed nucleus of the stria terminalis (BNST) is a forebrain region highly responsive to stress that expresses corticotropin-releasing hormone (CRH) and implicated in mood disorders, such as anxiety. However, exact mechanism by which chronic induces CRH-mediated dysfunction BNST maladaptive behaviors remains unclear. Here, we first confirmed selective acute optogenetic activation oval (ovBNST) increases avoidance male mice. Next, found 6 week variable mild (CVMS) paradigm resulted increased cellular excitability ovBNST CRH neurons potentiating mEPSC amplitude, altering resting membrane potential, diminishing M-currents (a voltage-gated K + current stabilizes potential) ex vivo slices. CVMS also c-fos cells following handling. We next investigated potential molecular underlying electrophysiological effects observed pituitary adenylate cyclase-activating polypeptide (PACAP; upstream regulator) but decreased striatal-enriched protein tyrosine phosphatase STEP inhibitor) ovBNST. Interestingly, were reversed CRHR1-selective antagonist R121919 application. activated kinase A (PKA) BNST, infusion PKA-selective H89 into CVMS. Coadministration PKA agonist forskolin prevented beneficial R121919. Finally, induced an increase surface expression phosphorylated GluR1 (S845) BNST. Collectively, these findings highlight novel indispensable stress-induced role for PKA-dependent CRHR1 signaling activating mediating behaviors. SIGNIFICANCE STATEMENT Chronic rodents. precise mechanisms remain demonstrate activates (CRH)-associated amplitude decreasing M-current These alterations mediated A-dependent signaling. Our results thus importance disorders.

Язык: Английский

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Behavioral and brain mechanisms mediating conditioned flight behavior in rats

Scientific Reports, Год журнала: 2021, Номер 11(1)

Опубликована: Апрель 15, 2021

Abstract Environmental contexts can inform animals of potential threats, though it is currently unknown how context biases the selection defensive behavior. Here we investigated context-dependent flight responses with a Pavlovian serial-compound stimulus (SCS) paradigm that evokes freeze-to-flight transitions. Similar to previous work in mice, show male and female rats display flight-like behavior SCS paradigm. Flight was dependent on contextual fear insofar as only evoked shock-associated reduced conditioning after extinction. expressed white noise regardless temporal order within compound. Nonetheless, received unpaired trials did not SCS, indicating associative. Finally, pharmacological inactivation two brain regions critical expression fear, central nucleus amygdala (CeA) bed stria terminalis (BNST), attenuates both responses. All these effects were similar rats. This demonstrates summate cued innate drive high state transition from post-encounter circa-strike modes.

Язык: Английский

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Oxytocin Promotes Accurate Fear Discrimination and Adaptive Defensive Behaviors

Frontiers in Neuroscience, Год журнала: 2020, Номер 14

Опубликована: Сен. 23, 2020

The nonapeptide, oxytocin (OT), known for its role in social bonding and attachment formation, has demonstrated anxiolytic properties animal models human studies. However, the regulation of fear responses appears more complex, brain site-specific, sex-specific, dependent on a prior stress history. Studies have shown that OT neurons hypothalamus are activated during cued contextual conditioning recall, highlighting recruitment endogenous system learning. is released into extended amygdala, which contains central nucleus amygdala (CeA) bed stria terminalis (BNST), both critical anxiety-like behaviors. Behavioral studies report CeA reduces responses; whereas BNST, receptor (OTR) neurotransmission facilitates to un-signaled, diffuse threats. These ostensibly contrasting behavioral effects support growing evidence works promote discrimination by reducing or threats, yet strengthening imminent predictable Recent from basolateral (BLA) this notion show activation OTR BLA increasing discrete cues. Also, transmission been mediate switch passive freezing active escape behaviors confrontation with an imminent, escapable threat but reduce reactivity distant Therefore, increase salience relevant threat-signaling cues distant, Lastly, signaling underlie emotional between conspecifics time distress, fear, buffering fear. As enhance positive negative experiences, it can also serve as warning against potential threats networks. Here, we extend hypothesis proposing enhances environmental non-social contexts, such promotes defensive

Язык: Английский

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Sex Differences in BNST and Amygdala Activation by Contextual, Cued, and Unpredictable Threats

eNeuro, Год журнала: 2021, Номер 9(1), С. ENEURO.0233 - 21.2021

Опубликована: Дек. 15, 2021

Abstract Fear and anxiety can be described as emotional physical responses to predictable unpredictable threats. While the amygdala is necessary for context cued fear conditioning, bed nucleus of stria terminalis (BNST) important anxiety-like behavior conditioned diffuse and/or However, we still lack knowledge about how BNST nuclei act in coordination. Moreover, incidence disorders posttraumatic stress disorder (PTSD) substantially higher women than men, but most studies conditioning are conducted male rodents. Here, asked whether lateral, basal, central active during expression female rats using FOS immunohistochemistry. We first show that indeed involved males, not females. The lateral was both sexes expression. next trained animals tone cues paired with an unconditioned stimulus (US), or which were unpaired US, thus nonpredictive. Females displayed greater these tones males. upregulated basal sexes. differential processing by males females highlights need acknowledge sex differences memory.

Язык: Английский

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Dynamic Threat Processing

Journal of Cognitive Neuroscience, Год журнала: 2018, Номер 31(4), С. 522 - 542

Опубликована: Дек. 4, 2018

During real-life situations, multiple factors interact dynamically to determine threat level. In the current fMRI study involving healthy adult human volunteers, we investigated interactions between proximity, direction (approach vs. retreat), and speed during a dynamic threat-of-shock paradigm. As measure of threat-evoked physiological arousal, skin conductance responses were recorded scanning. Some brain regions tracked individual threat-related factors, others also sensitive combinations these variables. particular, signals in anterior insula interaction proximity where approach versus retreat stronger when was closer compared with farther. A parallel proximity-by-direction observed responses. right amygdala, by interaction, but intriguingly opposite as insula; bed nucleus stria terminalis, an effect whereas periaqueductal gray/midbrain (the latter detected exploratory analyses not voxelwise fashion). Together, our refines understanding mechanisms involved aversive anticipation brain. Importantly, it emphasizes that processing should be understood manner is both context-sensitive dynamic.

Язык: Английский

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Threat imminence dictates the role of the bed nucleus of the stria terminalis in contextual fear

Neurobiology of Learning and Memory, Год журнала: 2019, Номер 167, С. 107116 - 107116

Опубликована: Ноя. 15, 2019

Язык: Английский

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Somatostatin Neurons of the Bed Nucleus of Stria Terminalis Enhance Associative Fear Memory Consolidation in Mice

Journal of Neuroscience, Год журнала: 2021, Номер 41(9), С. 1982 - 1995

Опубликована: Янв. 19, 2021

Excessive fear learning and generalized, extinction-resistant memories are core symptoms of anxiety trauma-related disorders. Despite significant evidence from clinical studies reporting hyperactivity the bed nucleus stria terminalis (BNST) under these conditions, role BNST in expression is still not clarified. Here, we tested how modulates male mice using a chemogenetic approach. Activation GABAergic neurons during conditioning or memory consolidation resulted enhanced cue-related recall. Importantly, activation had no acute impact on recalls, but it recall subsequently, potentially via altered activity downstream regions. Enhanced could be replicated by selectively activating somatostatin (SOM), corticotropin-releasing factor (CRF), BNST, which was accompanied increased generalization. Our findings suggest modulation strength specific circuits BNST. SIGNIFICANCE STATEMENT The mediates different defensive behaviors, its connections implicate integrative modulatory formation; however, involvement has yet to elucidated detail. data highlight that stimulation enhances formation without direct effects expression. study identified (SOM) cells within extended amygdala as promoting formation. These underline importance maladaptive formation, indicating elevated potential vulnerability

Язык: Английский

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