Neurobiology Unit, Institute for Biotechnology and Biomedicine (BIOTECMED), Universitat de València, 46100, Spain; Spanish National Network for Research in Mental Health CIBERSAM, 28029, Spain; Fundación Investigación Hospital Clínico de Valencia, INCLIVA, 46010 Valencia, Spain.
Neurobiology Unit, Institute for Biotechnology and Biomedicine (BIOTECMED), Universitat de València, 46100, Spain.
Neurobiol Dis. 2024 Oct 1;200:106642. doi: 10.1016/j.nbd.2024.106642. Epub 2024 Aug 22.
Adverse experiences during infancy and adolescence have an important and enduring effect on the brain and are predisposing factors for mental disorders, particularly major depression. This impact is particularly notable in regions with protracted development, such as the prefrontal cortex. The inhibitory neurons of this cortical region are altered by peripubertal stress (PPS), particularly in female mice. In this study we have explored whether the inhibitory circuits of the thalamus are impacted by PPS in male and female mice. This diencephalic structure, as the prefrontal cortex, also completes its development during postnatal life and is affected by adverse experiences. The long-term changes induced by PPS were exclusively found in adult female mice. We have found that PPS increases depressive-like behavior and induces changes in parvalbumin-expressing (PV+) cells of the thalamic reticular nucleus (TRN). We observed reductions in the volume of the TRN, together with those of parameters related to structures/molecules that regulate the plasticity and connectivity of PV+ cells: perineuronal nets, matricellular structures surrounding PV+ neurons, and the polysialylated form of the neural cell adhesion molecule (PSA-NCAM). The expression of the GluN1, but not of GluN2C, NMDA receptor subunit was augmented in the TRN after PPS. An increase in the fluorescence intensity of PV+ puncta was also observed in the synaptic output of TRN neurons in the lateral posterior thalamic nucleus. These results demonstrate that the inhibitory circuits of the thalamus, as those of the prefrontal cortex, are vulnerable to the effects of aversive experiences during early life, particularly in females. This vulnerability is probably related to the protracted development of the TRN and might contribute to the development of psychiatric disorders.
婴儿期和青少年期的不良经历对大脑有重要且持久的影响,是精神障碍的促成因素,尤其是重度抑郁症。这种影响在发育过程较长的区域尤为明显,如前额叶皮层。该皮质区域的抑制性神经元会被青春期前应激(PPS)改变,尤其是在雌性小鼠中。在这项研究中,我们探讨了 PPS 是否会影响雄性和雌性小鼠丘脑的抑制性回路。与前额叶皮层一样,这个间脑结构也在出生后生命中完成发育,并受到不良经历的影响。PPS 引起的长期变化仅在成年雌性小鼠中发现。我们发现,PPS 会增加类似抑郁的行为,并诱导丘脑网状核(TRN)中表达 Parvalbumin 的(PV+)细胞发生变化。我们观察到 TRN 体积减小,同时与调节 PV+细胞可塑性和连通性的结构/分子的参数也减小:神经元周围网络、围绕 PV+神经元的基质细胞结构,以及神经细胞黏附分子的多涎酸化形式(PSA-NCAM)。PPS 后,TRN 中 NMDA 受体亚单位 GluN1 的表达增加,但 GluN2C 没有增加。在外侧丘脑后核的 TRN 神经元的突触输出中,还观察到 PV+ 斑点的荧光强度增加。这些结果表明,丘脑的抑制性回路,如同前额叶皮层的回路一样,容易受到生命早期不良经历的影响,尤其是在女性中。这种易感性可能与 TRN 的发育过程较长有关,并且可能有助于精神障碍的发展。