Center for Regenerative Medicine, Massachusetts General Hospital, Boston, MA, 02114, USA; Harvard Stem Cell Institute, Cambridge, MA, 02138, USA; Department of Psychiatry, Massachusetts General Hospital, Harvard Medical School, Boston, MA, 02114, USA.
Center for Regenerative Medicine, Massachusetts General Hospital, Boston, MA, 02114, USA; Harvard Stem Cell Institute, Cambridge, MA, 02138, USA; Department of Psychiatry, Massachusetts General Hospital, Harvard Medical School, Boston, MA, 02114, USA; BROAD Institute of Harvard and MIT, Cambridge, MA, 02142, USA.
Behav Brain Res. 2021 Feb 5;399:112917. doi: 10.1016/j.bbr.2020.112917. Epub 2020 Sep 16.
Hippocampal circuitry is continuously modified by integration of adult-born dentate granule cells (DGCs). Prior work has shown that enhancing adult hippocampal neurogenesis decreases interference or overlap or conflict between ensembles of similar contexts and promotes discrimination of a shock-associated context from a similar, neutral context. However, the impact of enhanced integration of adult-born neurons on hippocampal network activity or downstream circuits such as the dorsolateral septum that mediate defensive behavioral responses is poorly understood. Here, we first replicated our finding that genetic expansion of the population of adult-born dentate granule cells (8 weeks and younger) promotes contextual fear discrimination. We found that enhanced contextual fear discrimination is associated with greater c-Fos expression in discrete hippocampal subfields along the proximo-distal and dorsoventral axis. Examination of the dorsolateral septum revealed an increase in activation of somatostatin expressing neurons consistent with recent characterization of these cells as calibrators of defensive behavior. Together, these findings begin to shed light on how genetically enhancing adult hippocampal neurogenesis affects activity of hippocampal-dorsolateral septal circuits.
海马回路通过成年新生齿状回颗粒细胞（DGC）的整合不断得到修饰。先前的研究表明，增强成年海马神经发生可以减少相似背景的集合之间的干扰、重叠或冲突，并促进对与冲击相关的背景与相似的中性背景的区分。然而，成年新生神经元整合增强对海马网络活动或下游回路（如介导防御行为反应的外侧隔核）的影响知之甚少。在这里，我们首先复制了我们的发现，即成年新生齿状回颗粒细胞（8 周龄及以下）群体的遗传扩展促进了情境恐惧的辨别。我们发现，增强的情境恐惧辨别与沿近-远轴和背-腹轴离散海马亚区中 c-Fos 表达的增加有关。对外侧隔核的检查显示，表达生长抑素的神经元的激活增加，这与这些细胞作为防御行为校准器的最近特征一致。总之，这些发现开始阐明如何通过遗传增强成年海马神经发生来影响海马-外侧隔核回路的活动。
