Parvalbumin positive (PV+) interneurons play a pivotal role in cognition and are known to be regulated developmentally and by ovarian hormones. The onset of puberty represents the end of a period of optimal learning when impairments in synaptic plasticity are observed in the CA1 hippocampus of female mice. Therefore, we tested whether the synaptic inhibitory current generated by PV+ interneurons is increased at puberty and contributes to these deficits in synaptic plasticity. To this end, the spontaneous inhibitory postsynaptic current (sIPSC) was recorded using whole-cell patch-clamp techniques from CA1 pyramidal cells in the hippocampal slice before (PND 28–32) and after the onset of puberty in female mice (~PND 35–44, assessed by vaginal opening). sIPSC frequency and amplitude were significantly increased at puberty, but these measures were reduced by 1 μM DAMGO [1 μM, (D-Ala², N-MePhe⁴, Gly-ol)-enkephalin], which silences PV+ activity via μ-opioid receptor targets. At puberty, dendritic branching of PV+ interneurons in GAD67-GFP mice was increased, while expression of the δ subunit of the GABA_A receptor (GABAR) on these interneurons decreased. Both frequency and amplitude of sIPSCs were significantly increased in pre-pubertal mice with reduced δ expression, suggesting a possible mechanism. Theta burst induction of long-term potentiation (LTP), an in vitro model of learning, is impaired at puberty but was restored to optimal levels by DAMGO administration, implicating inhibition via PV+ interneurons as one cause. Administration of the neurosteroid/stress steroid THP (30 nM, 3α-OH, 5α-pregnan-20-one) had no effect on sIPSCs. These findings suggest that phasic inhibition generated by PV+ interneurons is increased at puberty when it contributes to impairments in synaptic plasticity. These results may have relevance for the changes in cognitive function reported during early adolescence.

小白蛋白阳性（PV +）中间神经元在认知中起关键作用，并且已知在发育过程中受到卵巢激素的调节。当在雌性小鼠的CA1海马中观察到突触可塑性受损时，青春期的开始代表最佳学习期的结束。因此，我们测试了由PV +中间神经元产生的突触抑制电流是否在青春期增加，并有助于这些突触可塑性的缺陷。为此，在雌性小鼠青春期发作之前（PND 28-32），使用海马切片CA1锥体细胞的全细胞膜片钳技术记录了自发抑制突触后电流（sIPSC）（〜PND 35 –44，通过阴道开口评估）。sIPSC的频率和振幅在青春期显着增加，²，N-MePhe ⁴，Gly-ol）-脑啡肽]，它使PV +活性沉默通过μ阿片受体靶标。青春期，GAD67-GFP小鼠中PV +中间神经元的树突分支增加，而这些中间神经元上的GABA _A受体（GABAR）δ亚基的表达减少。sIPSCs的频率和幅度在青春期前的δ表达降低的小鼠中均显着增加，提示可能的机制。长期增强（LTP）的Theta爆发诱导体外 的学习模型，在青春期受损，但通过DAMGO给药恢复到最佳水平，这意味着抑制 通过PV +中间神经元是原因之一。神经类固醇/应激类固醇THP（30 nM，3α-OH，5α-pregnan-20-one）的给药对sIPSC没有影响。这些发现表明，PV +中间神经元产生的阶段性抑制作用在青春期时会增加，这会导致突触可塑性受损。这些结果可能与青春期早期报道的认知功能改变有关。