Understanding Emotions: Origins and Roles of the Amygdala

Biomolecules, Год журнала: 2021, Номер 11(6), С. 823 - 823

Опубликована: Май 31, 2021

Emotions arise from activations of specialized neuronal populations in several parts the cerebral cortex, notably anterior cingulate, insula, ventromedial prefrontal, and subcortical structures, such as amygdala, ventral striatum, putamen, caudate nucleus, tegmental area. Feelings are conscious, emotional experiences these that contribute to networks mediating thoughts, language, behavior, thus enhancing ability predict, learn, reappraise stimuli situations environment based on previous experiences. Contemporary theories emotion converge around key role amygdala central brain structure constantly evaluates integrates a variety sensory information surroundings assigns them appropriate values dimensions, valence, intensity, approachability. The participates regulation autonomic endocrine functions, decision-making adaptations instinctive motivational behaviors changes through implicit associative learning, short- long-term synaptic plasticity, activation fight-or-flight response via efferent projections its nucleus cortical structures.

Язык: Английский

---

The glucagon-like peptide-1 (GLP-1) analogue semaglutide reduces alcohol drinking and modulates central GABA neurotransmission

JCI Insight, Год журнала: 2023, Номер 8(12)

Опубликована: Май 16, 2023

Growing evidence indicates that the glucagon-like peptide-1 (GLP-1) system is involved in neurobiology of addictive behaviors, and GLP-1 analogues may be used for treatment alcohol use disorder (AUD). Here, we examined effects semaglutide, a long-acting analogue, on biobehavioral correlates rodents. A drinking-in-the-dark procedure was to test semaglutide binge-like drinking male female mice. We also tested dependence-induced rats, as well acute spontaneous inhibitory postsynaptic currents (sIPSCs) from central amygdala (CeA) infralimbic cortex (ILC) neurons. Semaglutide dose-dependently reduced mice; similar effect observed intake other caloric/noncaloric solutions. rats. increased sIPSC frequency CeA ILC neurons alcohol-naive suggesting enhanced GABA release, but had no overall transmission alcohol-dependent In conclusion, analogue decreased across different models species modulated neurotransmission, providing support clinical testing potentially novel pharmacotherapy AUD.

Язык: Английский

---

Central amygdala micro-circuits mediate fear extinction

Nature Communications, Год журнала: 2021, Номер 12(1)

Опубликована: Июль 6, 2021

Fear extinction is an adaptive process whereby defensive responses are attenuated following repeated experience of prior fear-related stimuli without harm. The formation memories involves interactions between various corticolimbic structures, resulting in reduced central amygdala (CEA) output. Recent studies show, however, the CEA not merely output relay fear but contains multiple neuronal subpopulations that interact to calibrate levels responding. Here, by integrating behavioural, vivo electrophysiological, anatomical and optogenetic approaches mice we demonstrate produces reversible, stimulus- context-specific changes conditioned functionally genetically defined cell types lateral (CEl) medial (CEm) CEA. Moreover, show these alterations absent when deficient selective silencing protein kinase C delta-expressing (PKCδ) CEl neurons impairs extinction. Our findings identify inhibitory microcircuits act as critical elements within brain networks mediating

Язык: Английский

---

Astrocyte regulation of synaptic signaling in psychiatric disorders

Neuropsychopharmacology, Год журнала: 2022, Номер 48(1), С. 21 - 36

Опубликована: Май 16, 2022

Язык: Английский

---

Neural Functions of Hypothalamic Oxytocin and its Regulation

ASN NEURO, Год журнала: 2022, Номер 14, С. 175909142211007 - 175909142211007

Опубликована: Янв. 1, 2022

Oxytocin (OT), a nonapeptide, has variety of functions. Despite extensive studies on OT over past decades, our understanding its neural functions and their regulation remains incomplete. is mainly produced in neurons the supraoptic nucleus (SON), paraventricular (PVN) accessory nuclei between SON PVN. exerts neuromodulatory effects brain spinal cord. While magnocellular PVN innervate pituitary forebrain regions, parvocellular brainstem cord, two sets have close interactions histologically functionally. expression occurs at early life to promote mental physical development, while subsequent decrease later stage accompanies aging diseases. Adaptive changes this system, however, take place under different conditions upon maturation release machinery. can modulate social recognition behaviors, learning memory, emotion, reward, other higher also regulates eating drinking, sleep wakefulness, nociception analgesia, sexual behavior, parturition, lactation instinctive behaviors. autonomic nervous somatic specialized senses. Notably, modulatory same function conditions. Such divergence may derive from connections, receptor gene dimorphism methylation, complex with hormones. In review, underlying mechanisms as well perspectives clinical usage are presented.

Язык: Английский

---

Cell-type specific changes in PKC-delta neurons of the central amygdala during alcohol withdrawal

Translational Psychiatry, Год журнала: 2022, Номер 12(1)

Опубликована: Июль 20, 2022

The central amygdala (CeA) contains a diverse population of cells, including multiple subtypes GABAergic neurons, along with glia and epithelial cells. Specific CeA cell types have been shown to affect alcohol consumption in animal models dependence may be involved negative during withdrawal. We used single-nuclei RNA sequencing determine cell-type specificity differential gene expression the induced by Cells within were classified using unbiased clustering analyses identified based on known marker genes. Differential analysis was performed each cell-type. It revealed astrocytes neurons associated further subclassified into 13 clusters Analyzing transcriptomic responses these subclusters that exposure differentially expressed genes one subtype protein kinase C delta (PKCδ) expressing neurons. These results suggest PKCδ uniquely sensitive effects identify novel cells

Язык: Английский

---

Central amygdala astrocyte plasticity underlies GABAergic dysregulation in ethanol dependence

Translational Psychiatry, Год журнала: 2025, Номер 15(1)

Опубликована: Апрель 8, 2025

Dependence is a hallmark of alcohol use disorder characterized by excessive intake and withdrawal symptoms. The central nucleus the amygdala (CeA) key brain structure underlying synaptic behavioral consequences ethanol dependence. While accumulating evidence suggests that astrocytes regulate transmission behavior, there limited understanding role play in present study used combination viral labeling, super resolution confocal microscopy, 3D image analysis, slice electrophysiology to determine effects chronic intermittent (CIE) exposure on astrocyte plasticity CeA. During from CIE exposure, we observed increased GABA transmission, an upregulation astrocytic GAT3 levels, proximity processes near CeA synapses. Furthermore, levels were positively associated with voluntary drinking dependent rats. Slice confirmed was functional, as unmasked GAT3-sensitive tonic current A causal for dependence assessed using viral-mediated overexpression knockdown approaches. However, or had no effect somatic symptoms, dependence-escalated intake, aversion-resistant drinking, post-dependent male female Moreover, intra-CeA pharmacological inhibition did not alter drinking. Together, these findings indicate induces GABAergic dysregulation changes do appear be necessary related phenotypes

Язык: Английский

---

Astrocytic GABAergic Regulation in Alcohol Use and Major Depressive Disorders

Cells, Год журнала: 2024, Номер 13(4), С. 318 - 318

Опубликована: Фев. 9, 2024

Gamma-aminobutyric acid (GABA) is the major inhibitory neurotransmitter in central nervous system (CNS). Most GABAergic neurons synthesize GABA from glutamate and release it synaptic cleft CNS. However, astrocytes can also GABA, activating receptors neighboring physiological pathological conditions. As primary homeostatic glial cells brain, play a crucial role regulating homeostasis neurotransmission. Accumulating evidence demonstrates that astrocytic dysregulation implicated psychiatric disorders, including alcohol use disorder (AUD) depressive (MDD), most prevalent co-occurring disorders. Several current medications emerging pharmacological agents targeting levels are clinical trials for treating AUD MDD. This review offers concise summary of regulation We provide an overview understanding areas debate regarding mechanisms by which regulate CNS their potential significance molecular basis MDD, paving way toward future research directions therapeutic target within this field.

Язык: Английский

---

Sex Differences in Neural Networks Recruited by Frontloaded Binge Alcohol Drinking

bioRxiv (Cold Spring Harbor Laboratory), Год журнала: 2024, Номер unknown

Опубликована: Фев. 9, 2024

Abstract Frontloading is an alcohol drinking pattern where intake skewed toward the onset of access. The goal current study was to identify brain regions involved in frontloading. Whole imaging performed 63 C57Bl/6J (32 female and 31 male) mice that underwent 8 days binge using drinking-in-the-dark (DID) model. On 1-7, three hours into dark cycle, received 20% (v/v) or water for two hours. Intake measured 1-minute bins volumetric sippers, which facilitated analyses patterns. day were perfused 80 minutes DID session brains extracted. Brains then processed stain Fos protein iDISCO+. Following light sheet imaging, ClearMap2.1 used register Allen Brain Atlas detect Fos+ cells. For network analyses, patterns characterize as frontloaders non-frontloaders a recently developed change-point analysis. Based on this analysis groups (n = 20), 2), male 13) 8). There no differences total animals frontloaded versus those did not. Only characterized non-frontloaders, thus preventing group. Functional correlation matrices calculated each group from log 10 values. Euclidean distances these R values hierarchical clustering determine modules (highly connected regions). In males, access decreased modularity (3 both non-frontloaders) compared drinkers (7 modules). females, opposite effect observed. Alcohol (9 frontloaders) increased (5 These results suggest sex how consumption reorganizes functional architecture neural networks. Next, key identified. Connector hubs, primarily facilitate communication between modules, provincial within specific interest their important differing roles. 4 connector hubs 17 uniquely identified (i.e., not have status drinkers). represented hindbrain (e.g., locus coeruleus pontine gray) functionally striatal/cortical cortical amygdalar area) by paraventricular nucleus thalamus. 16 distributed across 9 frontloader drinker network. one region (the raphe pontis) hub sexes, suggesting frontloading males females may be driven different regions. conclusion, led fewer, but more densely connected, recruited sexes. leads reduction efficiency mice.

Язык: Английский

---

Synthetic, Mechanistic, and Biological Interrogation of Ginkgo biloba Chemical Space En Route to (−)-Bilobalide

Journal of the American Chemical Society, Год журнала: 2020, Номер 142(43), С. 18599 - 18618

Опубликована: Сен. 29, 2020

Here we interrogate the structurally dense (1.64 mcbits/Å3) GABAA receptor antagonist bilobalide, intermediates en route to its synthesis, and related mechanistic questions. 13C isotope labeling identifies an unexpected bromine migration α-selective, catalytic asymmetric Reformatsky reaction, ruling out allylation pathway. Experiment computation converge on driving forces behind two surprising observations. First, oxetane acetal persists in concentrated mineral acid (1.5 M DCl THF-d8/D2O); longevity is correlated destabilizing steric clash between substituents upon ring-opening. Second, a regioselective oxidation of des-hydroxybilobalide found rely lactone acidification through lone-pair delocalization, which leads extremely rapid intermolecular enolate equilibration. We also establish equivalent effects (−)-bilobalide nonconvulsive sesquiterpene (−)-jiadifenolide action potential-independent inhibitory currents at GABAergic synapses, using (+)-bilobalide as negative control. The high information density bilobalide distinguishes it from other scaffolds may characterize natural product (NP) space more generally. Therefore, include Python script quickly (ca. 132 000 molecules/min) calculate content (Böttcher scores), prove helpful identify important features NP space.

Язык: Английский

---