Top-down regulation of motivated behaviors via lateral septum sub-circuits

Molecular Psychiatry, Journal Year: 2022, Volume and Issue: 27(8), P. 3119 - 3128

Published: May 18, 2022

Abstract How does cognition regulate innate behaviors? While the cognitive functions of cortex have been extensively studied, we know much less about how can motivated behaviors to fulfill physiological, safety and social needs. Selection appropriate depends on external stimuli past experiences that helps scale priorities. With its abundant inputs from neocortical allocortical regions, lateral septum (LS) is ideally positioned integrate perception experience signals in order activity hypothalamic midbrain nuclei control behaviors. In addition, LS receives numerous subcortical modulatory inputs, which represent animal internal states also participate this regulation. perspective, argue sub-circuits distinct by integrating neural neocortical, neuromodulatory inputs. propose inhibition between may allow emergence functional units orchestrates competing

Language: Английский

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The Neuropsychology of Anxiety

Oxford University Press eBooks, Journal Year: 2024, Volume and Issue: unknown

Published: May 7, 2024

Abstract The Neuropsychology of Anxiety first appeared in 1982 as the volume Oxford Psychology Series, and it quickly established itself classic work on subject. It second edition (appearing 2000) have been cited at a steadily increasing rate passing 500/year 2017. field has continued to expand last quarter century necessitating this third edition. This completely updated revised (with many figures converted colour) retains original core concepts while expanding often simplifying details. includes new chapter prefrontal cortex, which integrates frontal hippocampal views anxiety an extensively modified personality providing basis for further developments Reinforcement Sensitivity Theory. book is essential postgraduate students researchers experimental psychology neuroscience, well all clinical psychologists psychiatrists.

Language: Английский

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Lateral septum-lateral hypothalamus circuit dysfunction in comorbid pain and anxiety

Molecular Psychiatry, Journal Year: 2023, Volume and Issue: 28(3), P. 1090 - 1100

Published: Jan. 16, 2023

Abstract Pain and anxiety comorbidities are a common health problem, but the neural mechanisms underlying comorbidity remain unclear. We propose that implies similar brain regions circuits, with lateral septum (LS) as major candidate, process pain anxiety. From results of behavioral neurophysiological experiments combined selective LS manipulation in mice, we find GABAergic neurons were critical for both Selective activation induced hyperalgesia anxiety-like behaviors. In contrast, inhibition reduced nocifensive withdrawal responses This was found two mouse models, one chronic inflammatory (induced by complete Freund’s adjuvant) restraint stress). Additionally, using TetTag chemogenetics to functionally mark neurons, acute stimulation could induce behaviors vice versa. Furthermore, show projection hypothalamus (LH) plays an important role regulation comorbidities. Our study revealed especially -LH circuit, modulation

Language: Английский

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Lateral septum adenosine A2A receptors control stress-induced depressive-like behaviors via signaling to the hypothalamus and habenula

Nature Communications, Journal Year: 2023, Volume and Issue: 14(1)

Published: April 5, 2023

Major depressive disorder ranks as a major burden of disease worldwide, yet the current antidepressant medications are limited by frequent non-responsiveness and significant side effects. The lateral septum (LS) is thought to control depression, however, cellular circuit substrates largely unknown. Here, we identified subpopulation LS GABAergic adenosine A

Language: Английский

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Prefrontal modulation of anxiety through a lens of noradrenergic signaling

Frontiers in Systems Neuroscience, Journal Year: 2023, Volume and Issue: 17

Published: April 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

Language: Английский

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Kisspeptin fiber and receptor distribution analysis suggests its potential role in central sensorial processing and behavioral state control

Journal of Neuroendocrinology, Journal Year: 2025, Volume and Issue: unknown

Published: March 10, 2025

Kisspeptin (KP) signaling in the brain is defined by anatomical distribution of KP-producing neurons, their fibers, receptors, and connectivity. Technological advances have prompted a re-evaluation these chemoanatomical aspects, originally studied early years after discovery KP its receptor Kiss1r. Previously, we characterized (Hernández et al. bioRxiv 2024) seven neuronal populations mouse at mRNA level, including two novel populations, examined response to gonadectomy. In this study, mapped fiber rats mice using immunohistochemistry under intact as well short- long-term post-gonadectomy conditions. Kiss1r expression was via RNAscope, relation vesicular GABA transporter (Slc32a1) whole brain, glutamate 2 (Slc17a6), Kiss1, Slc32a1 hypothalamic RP3V arcuate regions. We identified fibers 118 regions, primarily extra-hypothalamic areas associated with sensorial processing behavioral state control. KP-immunoreactive density were largely unchanged expressed prominently control regions such septal nuclei, suprachiasmatic nucleus, locus coeruleus, hippocampal layers, thalamic cerebellar structures. Co-expression Kiss1 observed suggesting both autocrine paracrine mechanisms. These findings enhance our understanding beyond reproductive functions, particularly regulation. This study opens new avenues for investigating KP's role controlling complex physiological processes, those unrelated reproduction.

Language: Английский

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Opioid-driven disruption of the septal complex reveals a role for neurotensin-expressing neurons in withdrawal

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2024, Volume and Issue: unknown

Published: Jan. 16, 2024

Because opioid withdrawal is an intensely aversive experience, persons with use disorder (OUD) often relapse to avoid it. The lateral septum (LS) a forebrain structure that important in aversion processing, and previous studies have linked the substance disorders. It unclear, however, which precise LS cell types might contribute maladaptive state of withdrawal. To address this, we used single-nucleus RNA-sequencing interrogate type specific gene expression changes induced by chronic morphine We discovered globally disrupted transcriptional profile types, but Neurotensin-expressing neurons (

Language: Английский

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Multimodal classification of neurons in the lateral septum

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2024, Volume and Issue: unknown

Published: Feb. 20, 2024

ABSTRACT The lateral septum (LS) is a nucleus in the ventral forebrain that modulates complex social and affective behaviors. Several distinct neuronal types have been described LS; however, full extent of this cellular molecular diversity remains unclear. We address gap by profiling transcriptional identity mature LS neurons originating from two progenitor lineages defined their anatomical location expression transcription factor Nkx2.1 . describe 12 molecularly subtypes fall into main groups: those with history without. discovered lineage share an enrichment select cell adhesion communication molecules. Despite this, we found developmental origins can exhibit significant similarities. then examined spatial relationships among LS, revealing each subtype occupies discrete domain. These domains are graded patterns gene correlate taxonomy neuron encode proteins involved synaptic signaling. Lastly, genetically labeled non-overlapping subgroups neurons, detailed connective, morphological, electrophysiological properties. Our findings offer deeper understanding heterogeneity paving way for future studies how these contribute to regulating emotional motivated

Language: Английский

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TrkB-dependent regulation of molecular signaling across septal cell types

Translational Psychiatry, Journal Year: 2024, Volume and Issue: 14(1)

Published: Jan. 23, 2024

The lateral septum (LS), a GABAergic structure located in the basal forebrain, is implicated social behavior, learning, and memory. We previously demonstrated that expression of tropomyosin kinase receptor B (TrkB) LS neurons required for novelty recognition. To better understand molecular mechanisms by which TrkB signaling controls we locally knocked down used bulk RNA-sequencing to identify changes gene downstream TrkB. knockdown induces upregulation genes associated with inflammation immune responses, downregulation synaptic plasticity. Next, generated one first atlases profiles cell types using single nucleus (snRNA-seq). identified markers broadly, specifically, as well all neuronal types. then investigated whether differentially expressed (DEGs) induced map specific Enrichment testing downregulated DEGs are broadly across clusters. analyses these uniquely LS, either plasticity or neurodevelopmental disorders. Upregulated enriched microglia, response inflammation, linked both neurodegenerative disease neuropsychiatric In addition, many regulating behaviors. summary, findings implicate critical regulator networks psychiatric disorders display deficits, including schizophrenia autism, diseases, Alzheimer's.

Language: Английский

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The role of the lateral septum in neuropsychiatric disease

Journal of Neuroscience Research, Journal Year: 2022, Volume and Issue: 100(7), P. 1422 - 1437

Published: April 20, 2022

Abstract The lateral septum (LS) is a structure in the midline of brain that interconnected with areas associated stress and feeding. This review highlights role LS anxiety, depression, eating disorders their comorbidity. There prevailing view anxiolytic. finds both anxiolytic anxiogenic. Furthermore, can promote inhibit Given these shared roles, represents common site for comorbidity neuropsychiatric disorders, therefore potential pharmacological target. crucial since currently available treatments are not always effective. Corticotrophin‐releasing factor 2 antagonists drugs treatment anxiety anorexia require further research. other trials binge eating, such as alpha‐adrenergic agonists, may fact food intake. It hoped advancements chemo‐ optogenetic techniques will allow future studies to profile specific neural connections function. information could facilitate our understanding underlying mechanisms, targets, psychiatric conditions.

Language: Английский

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