Harte-Hargrove Lauren C, Varga-Wesson Ada, Duffy Aine M, Milner Teresa A, Scharfman Helen E
The Nathan Kline Institute for Psychiatric Research, Center of Dementia Research, Orangeburg, New York 10962, New York University, Langone Medical Center, Departments of Child and Adolescent Psychiatry, and.
The Nathan Kline Institute for Psychiatric Research, Center of Dementia Research, Orangeburg, New York 10962, New York University, Langone Medical Center.
J Neurosci. 2015 Jan 28;35(4):1723-38. doi: 10.1523/JNEUROSCI.0820-14.2015.
The mossy fiber (MF) pathway is critical to hippocampal function and influenced by gonadal hormones. Physiological data are limited, so we asked whether basal transmission and long-term potentiation (LTP) differed in slices of adult male and female rats. The results showed small sex differences in basal transmission but striking sex differences in opioid receptor sensitivity and LTP. When slices were made from females on proestrous morning, when serum levels of 17β-estradiol peak, the nonspecific opioid receptor antagonist naloxone (1 μm) enhanced MF transmission but there was no effect in males, suggesting preferential opioid receptor-dependent inhibition in females when 17β-estradiol levels are elevated. The μ-opioid receptor (MOR) antagonist Cys2,Tyr3,Orn5,Pen7-amide (CTOP; 300 nm) had a similar effect but the δ-opioid receptor (DOR) antagonist naltrindole (NTI; 1 μm) did not, implicating MORs in female MF transmission. The GABAB receptor antagonist saclofen (200 μm) occluded effects of CTOP but the GABAA receptor antagonist bicuculline (10 μm) did not. For LTP, a low-frequency (LF) protocol was used because higher frequencies elicited hyperexcitability in females. Proestrous females exhibited LF-LTP but males did not, suggesting a lower threshold for synaptic plasticity when 17β-estradiol is elevated. NTI blocked LF-LTP in proestrous females, but CTOP did not. Electron microscopy revealed more DOR-labeled spines of pyramidal cells in proestrous females than males. Therefore, we suggest that increased postsynaptic DORs mediate LF-LTP in proestrous females. The results show strong MOR regulation of MF transmission only in females and identify a novel DOR-dependent form of MF LTP specific to proestrus.
苔藓纤维（MF）通路对海马功能至关重要，并受性腺激素影响。生理数据有限，因此我们研究了成年雄性和雌性大鼠脑片的基础传递和长时程增强（LTP）是否存在差异。结果显示，基础传递存在微小的性别差异，但阿片受体敏感性和LTP存在显著的性别差异。当在动情前期早晨（此时血清17β-雌二醇水平达到峰值）取雌性大鼠脑片时，非特异性阿片受体拮抗剂纳洛酮（1 μM）可增强MF传递，但对雄性大鼠无此作用，这表明当17β-雌二醇水平升高时，雌性大鼠存在优先的阿片受体依赖性抑制。μ-阿片受体（MOR）拮抗剂Cys2,Tyr3,Orn5,Pen7-酰胺（CTOP；300 nM）有类似作用，但δ-阿片受体（DOR）拮抗剂纳曲吲哚（NTI；1 μM）则无此作用，提示MOR参与雌性MF传递。GABAB受体拮抗剂巴氯芬（200 μM）可阻断CTOP的作用，但GABAA受体拮抗剂荷包牡丹碱（10 μM）则不能。对于LTP，采用低频（LF）方案，因为较高频率会引起雌性大鼠的过度兴奋。动情前期雌性大鼠表现出LF-LTP，而雄性大鼠则没有，这表明当17β-雌二醇升高时，突触可塑性的阈值较低。NTI可阻断动情前期雌性大鼠的LF-LTP，但CTOP则不能。电子显微镜显示，动情前期雌性大鼠锥体细胞上DOR标记的棘突比雄性大鼠更多。因此，我们认为突触后DOR增加介导了动情前期雌性大鼠的LF-LTP。结果表明，仅在雌性大鼠中MOR对MF传递有强烈调节作用，并确定了一种动情前期特有的新型DOR依赖性MF LTP形式。
