Tuna Tuğçe, Banks Tyler, Glickert Gregory, Sevinc Cem, Nair Satish S, Unal Gunes
Behavioral Neuroscience Laboratory, Department of Psychology, Boğaziçi University, Bebek, 34342, Istanbul, Turkey.
Neural Engineering Laboratory, Department of Electrical Engineering and Computer Science, University of Missouri, Columbia, MO, 65211, USA.
Brain Struct Funct. 2025 Jan 13;230(1):30. doi: 10.1007/s00429-024-02886-1.
Theta oscillations of the mammalian amygdala are associated with processing, encoding and retrieval of aversive memories. In the hippocampus, the power of the network theta oscillation is modulated by basal forebrain (BF) GABAergic projections. Here, we combine anatomical and computational approaches to investigate if similar BF projections to the amygdaloid complex provide an analogous modulation of local network activity. We used retrograde tracing with fluorescent immunohistochemistry to identify cholinergic and non-cholinergic parvalbumin- or calbindin-immunoreactive BF neuronal subgroups targeting the input (lateral and basolateral nuclei) and output (central nucleus and the central bed nucleus of the stria terminalis) regions of the amygdaloid complex. We observed a dense non-cholinergic, putative GABAergic projection from the ventral pallidum (VP) and the substantia innominata (SI) to the basolateral amygdala (BLA). The VP/SI axonal projections to the BLA were confirmed using viral anterograde tracing and transsynaptic labeling. We tested the potential function of this VP/SI-BLA pathway in a 1000-cell biophysically realistic network model, which incorporated principal neurons and three major interneuron groups of the BLA, together with extrinsic glutamatergic, cholinergic, and VP/SI GABAergic inputs. We observed in silico that theta-modulation of VP/SI GABAergic projections enhanced theta oscillations in the BLA via their selective innervation of the parvalbumin-expressing local interneurons. Ablation of parvalbumin-, but not somatostatin- or calretinin-expressing, interneurons reduced theta power in the BLA model. These results suggest that long-range BF GABAergic projections may modulate network activity at their target regions through the formation of a common interneuron-type and oscillatory phase-specific disinhibitory motif.
哺乳动物杏仁核的θ振荡与厌恶记忆的处理、编码和提取有关。在海马体中，网络θ振荡的功率受基底前脑（BF）GABA能投射的调节。在此，我们结合解剖学和计算方法来研究向杏仁复合体的类似BF投射是否对局部网络活动提供类似的调节。我们使用荧光免疫组织化学逆行追踪来识别靶向杏仁复合体输入（外侧核和基底外侧核）和输出（中央核和终纹床核）区域的胆碱能和非胆碱能小白蛋白或钙结合蛋白免疫反应性BF神经元亚群。我们观察到从腹侧苍白球（VP）和无名质（SI）到基底外侧杏仁核（BLA）有密集的非胆碱能、假定的GABA能投射。使用病毒顺行追踪和跨突触标记证实了VP/SI向BLA的轴突投射。我们在一个包含BLA的主神经元和三个主要中间神经元群以及外在谷氨酸能、胆碱能和VP/SI GABA能输入的1000细胞生物物理真实网络模型中测试了这条VP/SI-BLA通路的潜在功能。我们在计算机模拟中观察到，VP/SI GABA能投射的θ调制通过其对表达小白蛋白的局部中间神经元的选择性支配增强了BLA中的θ振荡。消融表达小白蛋白而非生长抑素或钙视网膜蛋白的中间神经元可降低BLA模型中的θ功率。这些结果表明，长程BF GABA能投射可能通过形成一种共同的中间神经元类型和振荡相位特异性去抑制基序来调节其靶区域的网络活动。
