Disinhibition-assisted LTP as a method for testing role of neuronal circuits in behavior
Disinhibition-assisted LTP as a method for testing role of neuronal circuits in behavior
批准号:
9903868
负责人:
Alexei Morozov
金额:
$12.46万
依托单位国家:
美国
项目类别:
财政年份:
2019
资助国家:
美国
项目状态:
已结题
起止时间:
2019-07-20 至 2019-11-30
关键词:
AcuteAmygdaloid structureAnxietyAreaAttenuatedBehaviorBehavioralBrainBrain regionCellsCorticosteroneDataDevelopmentDiseaseDisinhibitionDopamineEmotional disorderEtiologyFailureFrightGlutamatesIn VitroInterneuronsLearningLocationLong-Term PotentiationMental DepressionMethodsModelingMusNeuronsNorepinephrineOutcomePathway interactionsPharmacologyPrefrontal CortexPresynaptic TerminalsPropertyProtocols documentationPsyche structurePublishingRoleSomatostatinStressStructureSynapsesSynaptic TransmissionTechniquesTest ResultTestingWorkanxiety-like behavioranxiety-related behaviorbasedesigner receptors exclusively activated by designer drugsexperimental studyin vivointerestneuronal circuitryneuronal patterningoptogeneticsprocess optimizationtooltraittransmission process
中文摘要
项目摘要
在发育、学习或发展为疾病的过程中,大脑经历了整形
突触改变以突触传递逐渐增加或减少为特征的变化建模
这种人为的改变对于理解它们的功能作用是必要的。最近
发展的光遗传和化学遗传技术允许神经元激活或抑制,
但它们的行为方式要么全有,要么全不,不允许对逐渐的突触变化进行建模。
同时,这种逐渐的变化可以通过诱导长时程增强(LTP)或
抑郁症,但这些技术并不是在大脑的所有区域都可靠地起作用,特别是在
抑制控制较强的区域,包括基底外侧杏仁核。在试行阶段
实验中,我们发现瞬时的化学发生或光发生抑制
生长抑素而不是小白蛋白阳性的中间神经元能够在前额叶诱导LTP。
杏仁核通路。根据这些发现和公布的数据,我们假设一个瞬变
抑制某些类型的局部GABA能神经元,并联合刺激
感兴趣的突触,将提供一种通用的手段,在远程输入到
活体局部主神经元。我们将在目标1中使用额叶前部杏仁核来验证这一假说。
电路,因为它的人工突触调制特别难实现,而
考虑到这一回路在相关行为特征中的作用,对这种调节的需求很高
精神疾病。在目标2中,我们将测试dmPFC-BLA中的突触有效性的预测
循环决定了两种结构之间的振荡同步,并影响焦虑-
类似的行为。这些预测是基于theta振荡同步的发现
BLA和dmPFC之间的关系随着开阔视野中先天焦虑的增加而增加,而光刺激
DmPFC内的BLA轴突终末显著增加升高的PLUS中的焦虑样行为
迷宫和空地。这项研究有望产生获得LTP的技术
连接dmPFC和dmPFC主神经元的谷氨酸能突触的理想大小
BLA。在这些通路中控制LTP的GABA能神经元的类别将被识别,以及
将开发它们的瞬时抑制以帮助LTP诱导的方法。此LTP
优化过程将为开发类似的LTP协议提供模板
大脑区域。DmPFC-BLA相互投射的突触效应在振荡中的作用
同步性和焦虑相关的特征将被确定,这将告知潜在的
在情绪障碍中对该通路进行有针对性的操作的方法。
英文摘要
Project Summary
During development, learning or progression towards disease, the brain undergoes plastic
changes characterized by gradual increases or decreases in synaptic transmission. Modeling
such changes by artificial means is necessary for understanding their functional role. Recently
developed optogenetic and chemogenetic techniques allow neuronal activation or suppression,
but they act in the all-or-none manner and do not allow modeling of gradual synaptic changes.
Meanwhile, such gradual changes can be obtained by inducing long-term potentiation (LTP) or
depression, but these techniques do not work reliably in all areas of the brain, particularly in the
areas with a strong inhibitory control, which include the basolateral amygdala. In the pilot
experiments, we found that a transient chemogenetic or optogenetic suppression of the
somatostatin- but not parvalbumin-positive interneurons enables LTP induction in the prefrontal-
amygdala pathway. Based on these findings and published data, we hypothesize that a transient
suppression of certain classes of the local GABAergic neurons, combined with stimulation of
synapses of interest, will provide a universal means for inducing LTP in the remote inputs to the
local principal neurons in vivo. We will test this hypothesis in Aim 1 using the prefrontal-amygdala
circuit, because its artificial synaptic modulation has been especially difficult to achieve, while
the need for such modulation is high given the role of this circuit in the behavioral traits relevant
to mental disease. In Aim 2, we will test predictions that synaptic efficacy in the dmPFC-BLA
loop determines oscillatory synchronization between the two structures and influences anxiety-
like behaviors. These predictions are based on findings that theta oscillations synchrony
between BLA and dmPFC increase with innate anxiety in the open field, and photostimulation of
BLA axonal terminals in dmPFC acutely increase anxiety-like behaviors in the elevated plus
maze and open field. The study is expected to produce techniques for obtaining LTP of a
desirable magnitude in glutamatergic synapses connecting principal neurons of dmPFC and
BLA. The classes of GABAergic neurons that gate LTP in these pathways will be identified, and
methods for their transient suppression to aid LTP induction will be developed. This LTP
optimization process will provide a template for developing analogous LTP protocols for other
brain areas. The role of synaptic efficacy of the dmPFC-BLA reciprocal projections in oscillatory
synchronization and anxiety-relevant traits will be determined, which will inform about potential
methods for targeted manipulation of that pathway in emotional disorders.
期刊论文(2)
专著(0)
科研奖励(0)
会议论文
DOI:
10.1117/1.nph.7.1.015007
发表时间:
2020-01-01
期刊:
Neurophotonics
影响因子:
5.3
作者:
[Ito, Wataru, Fusco, Brendon, Morozov, Alexei]
通讯作者:
Morozov, Alexei
Observational fear enhanced plasticity in dmPFC-BLA circuit as a modulator of affective behaviors
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批准号:10614980
-
项目类别:
-
资助金额:$40.0万
-
财政年份:2019
-
负责人:Alexei Morozov
-
依托单位:
Observational fear enhanced plasticity in dmPFC-BLA circuit as a modulator of affective behaviors
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批准号:10400827
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项目类别:
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资助金额:$40.0万
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财政年份:2019
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负责人:Alexei Morozov
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依托单位:
Observational fear enhanced plasticity in dmPFC-BLA circuit as a modulator of affective behaviors
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批准号:10159754
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项目类别:
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资助金额:$40.0万
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财政年份:2019
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负责人:Alexei Morozov
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依托单位:
Observational fear enhanced plasticity in dmPFC-BLA circuit as a modulator of affective behaviors
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批准号:9973171
-
项目类别:
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资助金额:$40.0万
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财政年份:2019
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负责人:Alexei Morozov
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依托单位:
Silent synapses and plasticity of prefrontal-amygdala pathway after emotional distress
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批准号:8953261
-
项目类别:
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资助金额:$24.15万
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财政年份:2015
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负责人:Alexei Morozov
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依托单位:
CA3-Restricted BDNF Knockout as a Model of Abnormal Traits in Social Behaviors
-
批准号:8686082
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项目类别:
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资助金额:$32.4万
-
财政年份:2012
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负责人:Alexei Morozov
-
依托单位:
CA3-Restricted BDNF Knockout as a Model of Abnormal Traits in Social Behaviors
-
批准号:8354468
-
项目类别:
-
资助金额:$32.4万
-
财政年份:2012
-
负责人:Alexei Morozov
-
依托单位:
CA3-Restricted BDNF Knockout as a Model of Abnormal Traits in Social Behaviors
-
批准号:8531355
-
项目类别:
-
资助金额:$32.4万
-
财政年份:2012
-
负责人:Alexei Morozov
-
依托单位:
Role of Rhythmic Oscillations in Neuronal Plasticity
-
批准号:7312902
-
项目类别:
-
资助金额:$0.0万
-
财政年份:--
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负责人:Alexei Morozov
-
依托单位:
Synaptic mechanisms of amygdala-dependent behaviors
-
批准号:8556968
-
项目类别:
-
资助金额:$102.24万
-
财政年份:--
-
负责人:Alexei Morozov
-
依托单位:
Control of Fear/Defensive Behavior by Brain Derived Neurotrophic Factor
-
批准号:7594562
-
项目类别:
-
资助金额:$49.51万
-
财政年份:--
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负责人:Alexei Morozov
-
依托单位:
Control of fear/cognition by MAP kinase signaling
-
批准号:7137876
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项目类别:
-
资助金额:$0.0万
-
财政年份:--
-
负责人:Alexei Morozov
-
依托单位:
Synaptic mechanisms of amygdala-dependent behaviors
-
批准号:8158142
-
项目类别:
-
资助金额:$132.58万
-
财政年份:--
-
负责人:Alexei Morozov
-
依托单位:
Role of Rhythmic Oscillations in Neuronal Plasticity
-
批准号:6824373
-
项目类别:
-
资助金额:$0.0万
-
财政年份:--
-
负责人:Alexei Morozov
-
依托单位:
Control of Fear/Defensive Behavior by Brain Derived Neurotrophic Factor
-
批准号:8556945
-
项目类别:
-
资助金额:$25.56万
-
财政年份:--
-
负责人:Alexei Morozov
-
依托单位:
Control of Fear/Defensive Behavior by Brain Derived Neurotrophic Factor
-
批准号:7969396
-
项目类别:
-
资助金额:$100.9万
-
财政年份:--
-
负责人:Alexei Morozov
-
依托单位:
Control of Fear Behavior by Brain Derived Neurotrophic F
-
批准号:6982745
-
项目类别:
-
资助金额:$0.0万
-
财政年份:--
-
负责人:Alexei Morozov
-
依托单位:
Synaptic mechanisms of amygdala-dependent behaviors
-
批准号:8342166
-
项目类别:
-
资助金额:$126.6万
-
财政年份:--
-
负责人:Alexei Morozov
-
依托单位:
Role of Rhythmic Oscillations in Neuronal Plasticity
-
批准号:7735166
-
项目类别:
-
资助金额:$6.99万
-
财政年份:--
-
负责人:Alexei Morozov
-
依托单位:
Synaptic mechanisms of amygdala-dependent behaviors
-
批准号:7735211
-
项目类别:
-
资助金额:$46.58万
-
财政年份:--
-
负责人:Alexei Morozov
-
依托单位: