Serotonergic modulation of nucleus reuniens in affective and cognitive behaviors

情感和认知行为中团聚核的血清素调节

• 批准号: 10303284
• 负责人: ROBERT Paul Vertes
• 金额: $ 41.11万
• 依托单位: FLORIDA ATLANTIC UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-09-01 至 2025-02-28
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10303284
• 关键词: Affect; Affective; Anatomy; Anxiety; Attention; Behavior; Behavior assessment; Behavioral; Behavioral Assay; Behavioral Paradigm; Brain Stem; Cannulas; Central Nervous System Diseases; Clozapine; Cognition; Cognitive; Communication; Deafferentation procedure; Development; Dorsal; Emotional; Executive Dysfunction; Fiber; Fright; Gap Junctions; Glutamates; Goals; Hippocampus (Brain); Impairment; Implant; Investigation; Laboratories; Link; Measures; Mediating; Memory; Mental Depression; Mental disorders; Microinjections; Modeling; Mood Disorders; Mus; Neurobehavioral Manifestations; Neurons; Obsessive-Compulsive Disorder; Odors; Output; Oxides; Pathology; Pathway interactions; Pharmacogenetics; Pharmacology; Population; Positioning Attribute; Prefrontal Cortex; Primates; Process; Prosencephalon; RNA Interference; Rattus; Regulation; Reuniens Thalamic Nucleus; Reversal Learning; Rodent; Role; Sampling; Serotonergic System; Serotonin; Short-Term Memory; Site; System; TPH2; Tactile; Technology; Testing; Thalamic structure; Theta Rhythm; Transgenic Organisms; Update; Viral Vector; Work; anxiety-like behavior; avoidance behavior; behavior test; cognitive function; designer receptors exclusively activated by designer drugs; emotional functioning; executive function; expectation; experimental study; flexibility; insight; nerve supply; neuropsychiatric disorder; neuroregulation; neurotoxin 5; novel therapeutic intervention; raphe nuclei; receptor; recruit; response; virtual

PROJECT SUMMARY The nucleus reuniens (RE) of the ventral midline thalamus sits as the nonpareil nexus of prefrontal-hippocampal communication. While RE selectively directs its output to cortical limbic targets including the hippocampus (HF) and orbitomedial prefrontal cortex (PFC), RE receives a diverse array of inputs, including a dense supply of serotonergic (5- HT) fibers from the dorsal (DR) and median (MR) raphe nuclei. While DR and MR form two distinct essentially nonoverlapping 5-HT pathways, RE serves as a key site of convergence as MR and DR both distribute heavily to the midline thalamus. While RE's interactions with PFCàHF circuitry have been linked to cognitive behaviors, virtually nothing is known regarding the neuromodulatory role of 5-HT in RE. With the present proposal, we intend to continue our investigation of RE by utilizing pharmacological and chemogenetic approaches in conjunction with behavioral testing to elucidate how 5-HT modulation of RE participates in affective, mnemonic, and executive functioning. We hypothesize that 5-HT influence of RE is essential to flexible behavior and quelling 5-HT input to RE will increase avoidance behavior and impair executive measures, with each of these behaviors recruiting specific raphe pathways. We will utilize a comprehensive battery of validated rat behavioral assays to assess: 1.) anxiety/avoidance behavior using an open field and elevated plus maze paradigm; 2.) spatial working memory and behavioral flexibility using a delayed nonmatch to sample t-maze paradigm; 3.) and attention and behavioral flexibility using an odor tactile attentional set shifting task. First in Aim 1, we will examine how 5-HT availability in RE affects behavior by locally depleting 5-HT using the neurotoxin 5,7- dihydroxytryptamine. In Aim 2a, we will examine the distinct contributions of DR and MR on RE on behavior by using the inhibitory hM4D DREADD receptor to selectively suppress raphe-RE terminals. In Aim 2b, we will use a TPH2-Cre rat model in combination with DREADD technology to selectively inhibit serotoninergic projections from DR or MR to RE. These aims will be the first to outline the specific contributions of 5-HT input to RE on behavior. These results will provide important information on how raphe-thalamic circuitry contributes to emotional and cognitive functioning and importantly how alterations of this system impact this symptomology in depression, anxiety, and other neuropsychiatric disorders.

项目总结

项目成果

Projections from the five divisions of the orbital cortex to the thalamus in the rat.

从大鼠眼眶皮层的五个部分到丘脑的投影。

• DOI: 10.1002/cne.25419
• 发表时间: 2023
• 期刊: The Journal of comparative neurology
• 作者: Vertes,RobertP;Hoover,WalterB;Witter,MennoP;Yanik,MehmetFatih;Rojas,AmandaKP;Linley,StephanieB
• 通讯作者: Linley,StephanieB