Top-down control of flight by a non-canonical cortico-amygdala pathway.

Survival requires the selection of appropriate behaviour in response to threats, and dysregulated defensive reactions are associated with psychiatric illnesses such as post-traumatic stress and panic disorder. Threat-induced behaviours, including freezing and flight, are controlled by neuronal circuits in the central amygdala (CeA); however, the source of neuronal excitation of the CeA that contributes to high-intensity defensive responses is unknown. Here we used a combination of neuroanatomical mapping, in vivo calcium imaging, functional manipulations and electrophysiology to characterize a previously unknown projection from the dorsal peduncular (DP) prefrontal cortex to the CeA.

The Neuroendocrine Impact of Acute Stress on Synaptic Plasticity.

Stress induces changes in nervous system function on different signaling levels, from molecular signaling to synaptic transmission to neural circuits to behavior-and on different time scales, from rapid onset and transient to delayed and long-lasting. The principal effectors of stress plasticity are glucocorticoids, steroid hormones that act with a broad range of signaling competency due to the expression of multiple nuclear and membrane receptor subtypes in virtually every tissue of the organism. Glucocorticoid and mineralocorticoid receptors are localized to each of the cellular compartments of the receptor-expressing cells-the membrane, cytosol, and nucleus.

Acute Ethanol Modulates Synaptic Inhibition in the Basolateral Amygdala via Rapid NLRP3 Inflammasome Activation and Regulates Anxiety-Like Behavior in Rats.

Chronic alcohol exposure leads to a neuroinflammatory response involving activation of the nucleotide-binding oligomerization domain-like receptor protein 3 (NLRP3) inflammasome and proinflammatory cytokine production. Acute ethanol (EtOH) exposure activates GABAergic synapses in the central and basolateral amygdala (BLA) , but whether this rapid modulation of synaptic inhibition is because of an acute inflammatory response and alters anxiety-like behavior in male and female animals is not known. Here, we tested the hypotheses that acute EtOH facilitates inhibitory synaptic transmission in the BLA by activating the NLRP3 inflammasome-dependent acute inflammatory response, that the alcohol-induced increase in inhibition is cell type and sex dependent, and that acute EtOH in the BLA reduces anxiety-like behavior.

The Role of Genetically Distinct Central Amygdala Neurons in Appetitive and Aversive Responding Assayed with a Novel Dual Valence Operant Conditioning Paradigm.

To survive, animals must meet their biological needs while simultaneously avoiding danger. However, the neurobiological basis of appetitive and aversive survival behaviors has historically been studied using separate behavioral tasks. While recent studies in mice have quantified appetitive and aversive conditioned responses simultaneously (Jikomes et al.

The role of genetically distinct central amygdala neurons in appetitive and aversive responding assayed with a novel dual valence operant conditioning paradigm.

Unlabelled: To survive, animals must meet their biological needs while simultaneously avoiding danger. However, the neurobiological basis of appetitive and aversive survival behaviors has historically been studied using separate behavioral tasks. While recent studies in mice have quantified appetitive and aversive conditioned responses simultaneously (Heinz et al.

Stress-induced glucocorticoid desensitizes adrenoreceptors to gate the neuroendocrine response to somatic stress in male mice.

Noradrenergic afferents to hypothalamic corticotropin releasing hormone (CRH) neurons provide a major excitatory drive to the hypothalamic-pituitary-adrenal (HPA) axis via α1 adrenoreceptor activation. Noradrenergic afferents are recruited preferentially by somatic, rather than psychological, stress stimuli. Stress-induced glucocorticoids feed back onto the hypothalamus to negatively regulate the HPA axis, providing a critical autoregulatory constraint that prevents glucocorticoid overexposure and neuropathology.

Critical periods when dopamine controls behavioral responding during Pavlovian learning.

Rationale: Learning the association between rewards and predictive cues is critical for appetitive behavioral responding. The mesolimbic dopamine system is thought to play an integral role in establishing these cue-reward associations. The dopamine response to cues can signal differences in reward value, though this emerges only after significant training.

Neurobiology: Novel peptide pathways impact threat discrimination.

Discriminating dangerous predictive stimuli from non-threatening stimuli is vital for maintaining optimal behavioral strategies. A new study finds that novel stress-related peptide pathways to the dopaminergic midbrain play a fundamental role in threat generalization.

Dopamine release and its control over early Pavlovian learning differs between the NAc core and medial NAc shell.

Dopamine neurons respond to cues to reflect the value of associated outcomes. These cue-evoked dopamine responses can encode the relative rate of reward in rats with extensive Pavlovian training. Specifically, a cue that always follows the previous reward by a short delay (high reward rate) evokes a larger dopamine response in the nucleus accumbens (NAc) core relative to a distinct cue that always follows the prior reward by a long delay (low reward rate).

Pattern of dopamine signaling during aversive events predicts active avoidance learning.

Learning to avoid aversive outcomes is an adaptive strategy to limit one's future exposure to stressful events. However, there is considerable variance in active avoidance learning across a population. The mesolimbic dopamine system contributes to behaviors elicited by aversive stimuli, although it is unclear if the heterogeneity in active avoidance learning is explained by differences in dopamine transmission.

Mechanistic insights into epigenetic modulation of ethanol consumption.

There is growing evidence that small-molecule inhibitors of epigenetic modulators, such as histone deacetylases (HDAC) and DNA methyltransferases (DNMT), can reduce voluntary ethanol consumption in animal models, but molecular and cellular processes underlying this behavioral effect are poorly understood. We used C57BL/6J male mice to investigate the effects of two FDA-approved drugs, decitabine (a DNMT inhibitor) and SAHA (an HDAC inhibitor), on ethanol consumption using two tests: binge-like drinking in the dark (DID) and chronic intermittent every other day (EOD) drinking. Decitabine but not SAHA reduced ethanol consumption in both tests.

Repeated social defeat stress enhances glutamatergic synaptic plasticity in the VTA and cocaine place conditioning.

Enduring memories of sensory cues associated with drug intake drive addiction. It is well known that stressful experiences increase addiction vulnerability. However, it is not clear how repeated stress promotes learning of cue-drug associations, as repeated stress generally impairs learning and memory processes unrelated to stressful experiences.

DREAM/calsenilin/KChIP3 modulates strategy selection and estradiol-dependent learning and memory.

Downstream regulatory element antagonist modulator (DREAM)/calsenilin(C)/K⁺ channel interacting protein 3 (KChIP3) is a multifunctional Ca²⁺-binding protein highly expressed in the hippocampus that inhibits hippocampus-sensitive memory and synaptic plasticity in male mice. Initial studies in our lab suggested opposing effects of DR/C/K3 expression in female mice. Fluctuating hormones that occur during the estrous cycle may affect these results.