Prefrontal circuit mechanisms of threat conditioning
Prefrontal circuit mechanisms of threat conditioning
批准号:
10332742
负责人:
Roger L Clem
金额:
$42.12万
依托单位国家:
美国
项目类别:
财政年份:
2018
资助国家:
美国
项目状态:
已结题
起止时间:
2018-04-01 至 2023-12-31
关键词:
AddressAmygdaloid structureAnimalsAreaAttenuatedAuditoryAxonBehaviorBehavioralBrainBrain regionCalciumCellsChemosensitizationComplexConditioned StimulusCre driverDataDesire for foodDiseaseDisinhibitionDorsalElectrophysiology (science)EmotionalExhibitsExtinction (Psychology)FreezingFrightGeneticGenetic RecombinationGoalsHumanHyperactivityImageInterneuronsInvestigationLabelLearningMedialMediatingMemoryModelingModificationMood DisordersMusNeuronal PlasticityNeuronsNucleus AccumbensOutputPanicPanic DisorderParvalbuminsPathologicPeptidesPhobiasPopulationPost-Traumatic Stress DisordersPrefrontal CortexProcessRecruitment ActivityReportingResearchRodentRoleSignal TransductionSliceSomatostatinSourceStimulusSynapsesSynaptic TransmissionSynaptic plasticitySystemTechniquesTestingThalamic structureTimeViralWorkbasebehavioral outcomebehavioral responseclassical conditioningconditioned fearconditioningemotion dysregulationemotional reactionexcitatory neuronexperienceexperimental studyimprovedin vivomicroendoscopemidbrain central gray substanceneglectneocorticalneural circuitoptogeneticsrecruitstimulus processingtransmission process
中文摘要
精神疾病,如恐惧症、恐慌和创伤后应激障碍(PTSD)都与之相关
英文摘要
Psychiatric conditions such as phobia, panic and post-traumatic stress disorder (PTSD) are associated with
heightened fear-related behavior. This has been attributed in part to increased acquisition and expression of
threat memory, which occurs when an innocuous stimulus encountered under threatening circumstances
becomes a potent trigger for defensive emotional reactions. Research indicates that this form of memory
engages the prelimbic cortex, a rodent brain region that is analogous to an area of pathological hyperactivity in
the human medial prefrontal cortex (mPFC). Prelimbic excitatory neurons are thought to mediate memory
expression by signaling to key downstream brain regions. However, the circuit and synaptic mechanisms
underlying memory-specific recruitment of these cells remain poorly understood. The purpose of this project is
to identify prelimbic synaptic changes associated with threat memory formation in mice, to elucidate the role of
neural circuits where these modifications occur, and to define specific prelimbic output connections that
mediate threat-related behaviors. Based on preliminary experiments, this work will focus sparse populations of
inhibitory interneurons that express the peptide marker somatostatin and exhibit increased excitatory synaptic
activity after threat learning. Our central hypothesis is that these cells undergo an increase in stimulus-related
activity after learning and that they function to suppress parvalbumin-containing interneurons and thereby
relieve a major brake on excitatory neuronal firing. In Aim 1, we will use brain slice electrophysiology to
examine synapses mediating elevated activity of somatostatin interneurons as well as their interaction with
parvalbumin interneurons. In Aim 2, we will use optogenetics and calcium-based imaging in freely behaving
animals to test the role of somatostatin and parvalbumin interneurons in threat memory expression. Finally, in
Aim 3, we will identify specific excitatory populations mediating behavioral outcomes of somatostatin
interneuron manipulations as well as establish downstream brain regions to which these neurons provide
synaptic input. This project represents the first attempt to establish how emotional learning alters complex
inhibitory stimulus processing to support mPFC memory functions, and will identify potential targets for
attenuating pathological activity and associated behaviors.
期刊论文(7)
专著(0)
科研奖励(0)
会议论文
登录
查看更多内容
DOI:
10.1016/j.nlm.2021.107504
发表时间:
2021-10
期刊:
Neurobiology of learning and memory
影响因子:
2.7
作者:
[Cummings KA, Lacagnina AF, Clem RL]
通讯作者:
Clem RL
DOI:
10.1016/j.neuron.2022.07.004
发表时间:
2022-09-21
期刊:
NEURON
影响因子:
16.2
作者:
[Cummings, Kirstie A., Bayshtok, Sabina, Dong, Tri N., Kenny, Paul J., Clem, Roger L.]
通讯作者:
Clem, Roger L.
DOI:
10.1016/j.brainresbull.2017.11.016
发表时间:
2018-07
期刊:
Brain research bulletin
影响因子:
3.8
作者:
[Lucas EK, Clem RL]
通讯作者:
Clem RL
DOI:
10.1038/s41598-021-02157-7
发表时间:
2021-11-22
期刊:
Scientific reports
影响因子:
4.6
作者:
[Roman-Ortiz C, Guevara JA, Clem RL]
通讯作者:
Clem RL
DOI:
10.1007/s00213-018-5001-x
发表时间:
2019-01
期刊:
Psychopharmacology
影响因子:
3.4
作者:
[Lucas EK, Wu WC, Roman-Ortiz C, Clem RL]
通讯作者:
Clem RL
共 6 条
Microcircuits governing conflicting memories of threat and safety
-
批准号:10753931
-
项目类别:
-
资助金额:$62.24万
-
财政年份:2023
-
负责人:Roger L Clem
-
依托单位:
Comparative Neuroanatomy at single-neuron resolution
-
批准号:10216577
-
项目类别:
-
资助金额:$75.84万
-
财政年份:2021
-
负责人:Roger L Clem
-
依托单位:
Cellular substrates of early life trauma
-
批准号:10100871
-
项目类别:
-
资助金额:$58.65万
-
财政年份:2020
-
负责人:Roger L Clem
-
依托单位:
Cellular substrates of early life trauma
-
批准号:10266111
-
项目类别:
-
资助金额:$55.71万
-
财政年份:2020
-
负责人:Roger L Clem
-
依托单位:
Cellular substrates of early life trauma
-
批准号:10441585
-
项目类别:
-
资助金额:$55.71万
-
财政年份:2020
-
负责人:Roger L Clem
-
依托单位:
Cellular substrates of early life trauma
-
批准号:10657416
-
项目类别:
-
资助金额:$55.71万
-
财政年份:2020
-
负责人:Roger L Clem
-
依托单位:
Noradrenergic circuit mechanisms of persistent fear
-
批准号:8979721
-
项目类别:
-
资助金额:$42.38万
-
财政年份:2014
-
负责人:Roger L Clem
-
依托单位:
Noradrenergic circuit mechanisms of persistent fear
-
批准号:8800033
-
项目类别:
-
资助金额:$42.38万
-
财政年份:2014
-
负责人:Roger L Clem
-
依托单位:
Noradrenergic circuit mechanisms of persistent fear
-
批准号:9223120
-
项目类别:
-
资助金额:$4.21万
-
财政年份:2014
-
负责人:Roger L Clem
-
依托单位:
Regulation of calcium-permeable AMPA receptors in associative memory
-
批准号:7996558
-
项目类别:
-
资助金额:$5.3万
-
财政年份:2010
-
负责人:Roger L Clem
-
依托单位:
Regulation of calcium-permeable AMPA receptors in associative memory
-
批准号:7753061
-
项目类别:
-
资助金额:$5.01万
-
财政年份:2010
-
负责人:Roger L Clem
-
依托单位:
Regulation of calcium-permeable AMPA receptors in associative memory
-
批准号:8238370
-
项目类别:
-
资助金额:$1.29万
-
财政年份:2010
-
负责人:Roger L Clem
-
依托单位: