Electrophysiological Markers of Social Function

理性：社会缺陷使精神分裂症的难治性症状失灵。杏仁核是 被认为调节这一行为，以及对NMDAR介导的谷氨酸的破坏 传播也有牵连。然而，对蜂窝和区域的详细了解 社会赤字背后的巡回机制是缺乏的。假设：我们认为扰乱发展 而杏仁基底外侧核(BLA)神经元上NMDAR的谷氨酸能输入功能可能会中断 获得并维持正常的社会行为。此外，增加休息活动，即噪音，在 BLA会导致正常信号处理中断和社交输入的信噪比(SNR)降低 来自皮质-边缘脑区。方法：我们将使用活体脑电，局部场电位 (LFP)和多单位记录在脑白质和海马区的社会行为以及电压敏感 染料成像(VSDI)和细胞内记录来自NMDAR信号中断的小鼠的切片。型号 系统将包括NMDAR1表达结构性降低(NRL-/-)的小鼠，这些小鼠在 使用NRIflx小鼠的脑电和社会交互作用以及杏仁核选择性减少NRL的小鼠 注射AAV-Cre。解释：数据将为使用功能磁共振成像解释大脑区域激活提供信息 精神分裂症和高危受试者的体表脑电(项目1)。我们还将研究新的药理作用 恢复静息和社会行为中血乳酸兴奋性-抑制性平衡的方法。 公益声明：精神分裂症患者社交困难，致残 并且对目前的治疗方法有抵抗力。大脑中被称为杏仁核的一部分被认为调节正常 社会互动，以及被称为NMDA受体的受体上的神经递质谷氨酸的中断， 与精神分裂症的正常社交问题有牵连。这个项目将 确定小鼠杏仁核NMDA受体上谷氨酸活性的中断是否会导致社交 如果用新药修复这种活动可以恢复正常的社会功能。

Rational: Social deficits are disabling, treatment refractory symptoms of schizophrenia. The amygdala is thought to modulate this behavior, and disruption of NMDA receptor (NMDAR) mediated glutamate transmission has been implicated as well. However, a detailed understanding of the cellular and regional circuit mechanisms underlying social deficits is lacking. Hypotheses: We propose that disrupted development and functioning of glutamatergic inputs to NMDARs on basolateral amygdala (BLA) neurons can disrupt acquisition and maintenance of normal social behavior. Furthermore, increased resting activity, i.e. noise, in BLA leads to disruption of normal signal processing and reduced signal-to-noise ratio (SNR) for social inputs from cortico-limbic brain regions. Approach: We will use in vivo electroencephalography, local field potentials (LFP) and multiunit recording in in BLA and hippocampus during social behavior as well as voltage sensitive dye imaging (VSDI) and intracellular recordings in slices from mice with disrupted NMDAR signaling. Model systems will include mice with constitutive reduction in NMDAR1 expression (NRl-/-) that have deficits in EEG and social interactions, as well as mice with amygdala-selective reduction in NRl using NRIflox mice with AAV-Cre injections. Interpretation: Data will inform interpretation of regional brain activation using fMRI and surface EEG (Project 1) in schizophrenia and at risk subjects. We will also examine novel pharmacologic approaches for restoration of excitatory-inhibitory balance in BLA at rest and during social behaviors. Public Welfare Statement: People with schizophrenia have difficulty in social interactions, which is disabling and resistant to current treatments. A part of the brain called the amygdala is thought to modulate normal social interactions, and disruption of the neurotransmitter glutamate at a receptor called the NMDA receptor, has been implicated in causing problems with normal social interactions in schizophrenia. This project will determine if disruption of glutamate activity at NMDA receptors in amygdala in mice can cause social deficits, and if fixing that activity with new medications could restore normal social function .