背景:与抑郁症相关的症状被认为是由大脑网络中信息处理的中断引起的。腹侧被盖区(VTA)影响基于奖励的行为,动机,上瘾,和精神疾病,包括抑郁症。内侧前脑束(MFB)的深部脑刺激(DBS),是治疗难治性抑郁症的新兴疗法。了解抑郁症相关的解剖网络对于理解其抗抑郁作用至关重要。
方法:弗林德斯敏感线(FSL),本研究使用了抑郁症的啮齿动物模型和Sprague-Dawley大鼠(每组n=10)。我们使用单突触追踪来映射VTA传出神经元的输入:VTA到NAc伏隔核(NAc)(核心和外壳)和VTA到前额叶皮层(PFC)。定量分析探讨了传入多样性和优势。
结果:VTA传出神经元接受不同的输入权重和主要的神经调节表现。值得注意的是,NAc核心投射的VTA神经元显示出来自背侧中缝的更强传入,而NAc壳投射VTA神经元显示来自皮层的较低输入强度,丘脑,FSL大鼠的透明带和前盖区。NAc壳投射VTA神经元在实验组中的连通性差异最大。
结论:缺乏解剖连接的功能特性是本研究的主要限制。应当注意狂犬病病毒的不完全标记和细胞毒性。
结论:这些发现为不同的VTA上升投影神经元的输入提供了第一个表征,揭示中脑-前脑系统连接体的关键差异。此外,这些差异支持MFBDBS神经调节抑郁症背景下这些电路的潜在网络效应.
The symptoms associated with depression are believed to arise from disruptions in information processing across brain networks. The ventral tegmental area (VTA) influences reward-based behavior, motivation, addiction, and psychiatric disorders, including depression. Deep brain stimulation (DBS) of the medial forebrain bundle (MFB), is an emerging therapy for treatment-resistant depression. Understanding the depression associated anatomical networks crucial for comprehending its antidepressant effects.
Flinders Sensitive Line (FSL), a rodent model of depression and Sprague-Dawley rats (n = 10 each) were used in this study. We used monosynaptic tracing to map inputs of VTA efferent neurons: VTA-to-NAc nucleus accumbens (NAc) (both core and shell) and VTA-to-prefrontal cortex (PFC). Quantitative analysis explored afferent diversity and strengths.
VTA efferent neurons receive a variety of afferents with varying input weights and predominant neuromodulatory representation. Notably, NAc-core projecting VTA neurons showed stronger afferents from dorsal raphe, while NAc shell-projecting VTA neurons displayed lower input strengths from cortex, thalamus, zona incerta and pretectal area in FSL rats. NAc shell-projecting VTA neurons showed the most difference in connectivity across the experimental groups.
Lack of functional properties of the anatomical connections is the major limitation of this study. Incomplete labeling and the cytotoxicity of the rabies virus should be made aware of.
These findings provide the first characterization of inputs to different VTA ascending projection neurons, shedding light on critical differences in the connectome of the midbrain-forebrain system. Moreover, these differences support potential network effects of these circuits in the context of MFB DBS neuromodulation for depression.