啮齿动物主动母性行为动态改变的神经机制

doi:10.3724/SP.J.1042.2018.01417

摘要/Abstract

摘要：

主动母性行为是雌性哺乳动物在哺乳期内有效照料幼崽的一种动机行为, 对幼崽的生存和行为发展有重要影响。证据显示, 啮齿动物的主动母性行为会经历从产后早期的发动和维持到晚期衰退的动态改变, 反映了雌鼠对幼崽奖赏价值阶段性变化的适应; 这一过程不仅涉及分娩激素事件开启下丘脑内侧视前区(MPOA)-中脑腹侧被盖(VTA)-伏隔核(NA)-腹侧苍白球(VP)通路, 还需要杏仁核基底外侧核(BLA)和内侧前额皮层(MPFC)等脑区对上述通路进行实时调节。哺乳期主动母性行为动态改变及其神经机制的研究, 可以加深对行为进化和早期发展的认识, 也对人类母亲产后抑郁等临床问题的干预有借鉴意义。本文首先利用条件化位置偏好(CPP)任务的行为学证据分析幼崽奖赏价值与主动母性行为动态改变的关系; 然后系统阐述调控这一动态改变的神经机制; 最后对未来需要研究的一些重要问题或方向进行探讨。

关键词: 主动母性行为, 动态改变, 奖赏价值, 神经机制

Abstract:

Active maternal behavior refers to a set of motivated behaviors that promote female mammals to effectively care for the pups during their lactation, so it has a vital important role for the survival and behavioral development in pups. Evidence has shown that the active maternal behavior in rodents could dynamically change from the onset and maintenance in early postpartum to the decline in late postpartum, which reflects female rodents’ adaptation to the stage changes of incentive values in pups. This process not only involves in the pathway of medial preoptic area (MPOA)-ventral tegmental area (VTA)-nucleus accumbens (NA)-ventral pallidum (VP) opened by hormone profile at parturition, but also requires the basolateral amygdala (BLA), medial prefrontal cortex (MPFC), and other areas to real-timely regulate this pathway. Studies on the dynamic changes about active maternal behavior and its neural mechanisms in lactating rodents could deepen our knowledge about the evolution and early development of behaviors, and also be helpful for the clinical intervention to postpartum depression in humans. This review illustrates the relationship between incentive values in pups and dynamic changes in active maternal behavior with evidence used by conditioned place preference (CPP), then systematically elaborates the neural mechanisms underlying dynamic changes of active maternal behavior, and finally discusses several major issues or future research directions.

Key words: active maternal behavior, dynamic changes, incentive values, neural mechanisms

中图分类号:

B845

张一帆, 齐星亮, 蔡厚德. (2018). 啮齿动物主动母性行为动态改变的神经机制. 心理科学进展 , 26(8), 1417-1428.

ZHANG Yifan, QI Xingliang, CAI Houde. (2018). Neural mechanisms underlying dynamic changes of active maternal behavior in rodents. Advances in Psychological Science, 26(8), 1417-1428.

图/表 1

图1 主动母性行为动态改变的神经通路机制注： (A) 产后早期 (发动); (B) 产后早期 (维持); (C) 产后晚期 (衰退)。实线段表示神经投射的功能增强, 虚线段表示神经投射的功能减弱; 末端为箭头的线段为兴奋性投射, 末端为圆点的线段为抑制性投射; 线段上的小圆圈处标注神经投射的递质类型; 虚线椭圆表示VP中可以被强化的神经回路。Amygdala=杏仁核; MeA/CA=杏仁核内侧核/皮质核; BLA=杏仁核基底外侧核; MPFC=内侧前额皮层; IL=边缘下区; PrL=边缘前区; Hypothalamus=下丘脑; PVN=室旁核; MPOA=内侧视前区; VTA=中脑腹侧被盖; NA=伏隔核; VP=腹侧苍白球; MSN=中型多棘神经元; DA=多巴胺; GLU=谷氨酸; GABA= γ-氨基丁酸; OT=催产素; OTR=催产素受体。

参考文献 63

1	陈磊磊, 聂莉娜, 李钰, 程鹏, 李鸣, 高军 . ( 2017). 五羟色胺系统对母性行为的调控及其机制. 心理科学进展, 25( 12), 2089-2098.
2	刘飞, 蔡厚德 . ( 2010). 情绪生理机制研究的外周与中枢神经系统整合模型. 心理科学进展, 18( 4), 616-622.
3	Afonso, V. M, King, S., Chatterjee D., & Fleming A. S . ( 2009). Hormones that increase maternal responsiveness affect accumbal dopaminergic responses to pup- and food-stimuli in the female rat. Hormones and Behavior, 56( 1), 11-23. doi: 10.1016/j.yhbeh.2009.02.003 URL
4	Afonso V. M., Shams W. M., Jin D., & Fleming A. S . ( 2013). Distal pup cues evoke dopamine responses in hormonally primed rats in the absence of pup experience or ongoing maternal behavior. Journal of Neuroscience, 33( 6), 2305-2312. doi: 10.1523/JNEUROSCI.2081-12.2013 URL
5	Afonso V. M., Sison M., Lovic V., & Fleming A. S . ( 2007). Medial prefrontal cortex lesions in the female rat affect sexual and maternal behavior and their sequential organization. Behavioral Neuroscience, 121( 3), 515-526. doi: 10.1037/0735-7044.121.3.515 URL
6	Atzil S., Hendler T., & Feldman R . ( 2011). Specifying the neurobiological basis of human attachment: Brain, hormones, and behavior in synchronous and intrusive mothers. Neuropsychopharmacology, 36( 13), 2603-2615. doi: 10.1038/npp.2011.172 URL
7	Balleine, B. W., & Dickinson, A . ( 1998). Goal-directed instrumental action: Contingency and incentive learning and their cortical substrates. Neuropharmacology, 37( 4-5), 407-419. doi: 10.1016/S0028-3908(98)00033-1 URL
8	Banerjee S. B., & Liu R. C . ( 2013). Storing maternal memories: Hypothesizing an interaction of experience and estrogen on sensory cortical plasticity to learn infant cues. Frontiers in Neuroendocrinology, 34( 4), 300-314. doi: 10.1016/j.yfrne.2013.07.008 URL
9	Benedetto L., Pereira M., Ferreira A., & Torterolo P . ( 2014). Melanin-concentrating hormone in the medial preoptic area reduces active components of maternal behavior in rats. Peptides, 58, 20-25. doi: 10.1016/j.peptides.2014.05.012 URL
10	Cortés-Mendoza J., Díaz de León-Guerrero S., Pedraza-Alva G., & Pérez-Martínez L . ( 2013). Shaping synaptic plasticity: The role of activity-mediated epigenetic regulation on gene transcription. International Journal of Developmental Neuroscience, 31( 6), 359-369.
11	Dalley J. W., Cardinal R. N., & Robbins T. W . ( 2004). Prefrontal executive and cognitive functions in rodents: Neural and neurochemical substrates. Neuroscience and Biobehavioral Reviews, 28, 771-784. doi: 10.1016/j.neubiorev.2004.09.006 URL
12	D'Cunha T. M., King S. J., Fleming A. S., & Lévy F . ( 2011). Oxytocin receptors in the nucleus accumbens shell are involved in the consolidation of maternal memory in postpartum rats. Hormones & Behavior, 59( 1), 14-21.
13	Dilgen J., Tejeda H. A., & O'Donnell P . ( 2013). Amygdala inputs drive feedforward inhibition in the medial prefrontal cortex. Journal of Neurophysiology, 110( 1), 221-229. doi: 10.1152/jn.00531.2012 URL
14	Dobolyi A., Grattan D. R., & Stolzenberg D. S . ( 2014). Preoptic inputs and mechanisms that regulate maternal responsiveness. Journal of Neuroendocrinology, 26( 10), 627-640. doi: 10.1111/jne.12185 URL
15	Febo M., Numan M., & Ferris C. F . ( 2005). Functional magnetic resonance imaging shows oxytocin activates brain regions associated with mother-pup bonding during suckling. Journal of Neuroscience, 25( 50), 11637-11644. doi: 10.1523/JNEUROSCI.3604-05.2005 URL
16	Fleming A. S., Ruble D., Krieger H., & Wong P. Y . ( 1997). Hormonal and experiential correlates of maternal responsiveness during pregnancy and the puerperium in human mothers. Hormones & Behavior, 31( 2), 145-158.
17	Gagnidze K., Weil Z. M., Faustino L. C., Schaafsma S. M., & Pfaff D. W . ( 2013). Early histone modifications in the ventromedial hypothalamus and preoptic area following oestradiol administration. Journal of Neuroendocrinology, 25( 10), 939-955. doi: 10.1111/jne.2013.25.issue-10 URL
18	Jin S. H., Blendy J. A., & Thomas S. A . ( 2005). Cyclic AMP response element-binding protein is required for normal maternal nurturing behavior. Neuroscience, 133( 3), 647-655. doi: 10.1016/j.neuroscience.2005.03.017 URL
19	Kesner R. P . ( 2000). Subregional analysis of mnemonic functions of the prefrontal cortex in the rat. Psychobiology, 28( 2), 219-228.
20	Killcross, S., & Coutureau, E . ( 2003). Coordination of actions and habits in the medial prefrontal cortex of rats. Cerebral Cortex, 13( 4), 400-408. doi: 10.1093/cercor/13.4.400 URL
21	Kim P., Strathearn L., & Swain J. E . ( 2016). The maternal brain and its plasticity in humans. Hormones & Behavior, 77, 113-123.
22	Kuroda K. O., Meaney M. J., Uetani N., Fortin Y., Ponton A., & Kato T . ( 2007). ERK-fosB signaling in dorsal MPOA neurons plays a major role in the initiation of parental behavior in mice. Molecular and Cellular Neuroscience, 36( 2), 121-131. doi: 10.1016/j.mcn.2007.05.010 URL
23	Laurent, H. K., & Ablow, J. C . ( 2012). A cry in the dark: Depressed mothers show reduced neural activation to their own infant’s cry. Social Cognitive & Affective Neuroscience, 7( 2), 125-134.
24	Lee A., Clancy S., & Fleming A. S . ( 1999). Mother rats bar-press for pups: Effects of lesions of the MPOA and limbic sites on maternal behavior and operant responding for pup-reinforcement. Behavioural Brain Research, 100( 1-2), 15-31. doi: 10.1016/S0166-4328(98)00109-0 URL
25	Li, M., & Fleming, A. S . ( 2003). The nucleus accumbens shell is critical for normal expression of pup-retrieval in postpartum female rats. Behavioural Brain Research, 145( 1-2), 99-111. doi: 10.1016/S0166-4328(03)00135-9 URL
26	Lonstein J. S., Lévy F., & Fleming A. S . ( 2015). Common and divergent psychobiological mechanisms underlying maternal behaviors in non-human and human mammals. Hormones and Behavior, 73, 156-185. doi: 10.1016/j.yhbeh.2015.06.011 URL
27	Marlin B. J., Mitre M., D'Amour J. A., Chao M. V., & Froemke R. C . ( 2015). Oxytocin enables maternal behaviour by balancing cortical inhibition. Nature, 520( 7548), 499-504. doi: 10.1038/nature14402 URL
28	Mattson, B. J., & Morrell, J. I . ( 2005). Preference for cocaine- versus pup-associated cues differentially activates neurons expressing either Fos or cocaine- and amphetamine- regulated transcript in lactating, maternal rodents. Neuroscience, 135( 2), 315-328. doi: 10.1016/j.neuroscience.2005.06.045 URL
29	Mattson B. J., Williams S., Rosenblatt J. S., & Morrell J. I . ( 2001). Comparison of two positive reinforcing stimuli: Pups and cocaine throughout the postpartum period. Behavioral Neuroscience, 115( 3), 683-694. doi: 10.1037/0735-7044.115.3.683 URL
30	Moltz, H., & Wiener, E . ( 1966). Effects of ovariectomy on maternal behavior of primiparous and multiparous rats. Journal of Comparative & Physiological Psychology, 62( 3), 382-387.
31	Nicola, S. M . ( 2007). The nucleus accumbens as part of a basal ganglia action selection circuit. Psychopharmacology, 191( 3), 521-550. doi: 10.1007/s00213-006-0510-4 URL
32	Numan, M . ( 2006). Hypothalamic neural circuits regulating maternal responsiveness toward infants. Behavioral and Cognitive Neuroscience Reviews, 5( 4), 163-190. doi: 10.1177/1534582306288790 URL
33	Numan M., Bress J. A., Ranker L. R., Gary A. J., Denicola A. L., Bettis J. K., & Knapp S. E . ( 2010). The importance of the basolateral/basomedial amygdala for goal-directed maternal responses in postpartum rats. Behavioural Brain Research, 214( 2), 368-376. doi: 10.1016/j.bbr.2010.06.006 URL
34	Numan M., Rosenblatt J. S., & Komisaruk B. R . ( 1977). Medial preoptic area and onset of maternal behavior in the rat. Journal of Comparative & Physiological Psychology, 91( 1), 146-164.
35	Numan, M., & Stolzenberg, D. S . ( 2009). Medial preoptic area interactions with dopamine neural systems in the control of the onset and maintenance of maternal behavior in rats. Frontiers in Neuroendocrinology, 30( 1), 46-64. doi: 10.1016/j.yfrne.2008.10.002 URL
36	Numan, M., & Young, L. J . ( 2016). Neural mechanisms of mother-infant bonding and pair bonding: Similarities, differences, and broader implications. Hormones and Behavior, 77, 98-112. doi: 10.1016/j.yhbeh.2015.05.015 URL
37	Olazábal D., Pereira M., Agrati D., Ferreira A., Fleming A. S., González-Mariscal G.,.. Uriarte N . ( 2013 a). New theoretical and experimental approaches on maternal motivation in mammals. Neuroscience and Biobehavioral Reviews, 37, 1860-1874. doi: 10.1016/j.neubiorev.2013.04.003 URL
38	Olazábal D., Pereira M., Agrati D., Ferreira A., Fleming A. S., González-Mariscal G.,.. Uriarte N . ( 2013 b). Flexibility and adaptation of the neural substrate that supports maternal behavior in mammals. Neuroscience and Biobehavioral Reviews, 37, 1875-1892. doi: 10.1016/j.neubiorev.2013.04.004 URL
39	Parada M., King S., Li M., & Fleming A. S . ( 2008). The roles of accumbal dopamine D1 and D2 receptors in maternal memory in rats. Behavioral Neuroscience, 122( 2), 368-376. doi: 10.1037/0735-7044.122.2.368 URL
40	Peña, C. J., & Champagne, F. A . ( 2015). Neonatal overexpression of estrogen receptor-α alters midbrain dopamine neuron development and reverses the effects of low maternal care in female offspring. Developmental Neurobiology, 75( 10), 1114-1124. doi: 10.1002/dneu.v75.10 URL
41	Pereira, M . ( 2016). Structural and functional plasticity in the maternal brain circuitry. In H. J. V. Rutherford & L. C. Mayes (Eds.), Maternal brain plasticity: Preclinical and human research and implications for intervention. New Directions for Child and Adolescent Development (no. 153, pp. 23-46). Wiley Periodicals, Inc.
42	Pereira, M., & Ferreira, A . ( 2016). Neuroanatomical and neurochemical basis of parenting: Dynamic coordination of motivational, affective and cognitive processes. Hormones and Behavior, 77, 72-85. doi: 10.1016/j.yhbeh.2015.08.005 URL
43	Pereira, M., & Morrell, J. I . ( 2009). The changing role of the medial preoptic area in the regulation of maternal behavior across the postpartum period: Facilitation followed by inhibition. Behavioural Brain Research, 205( 1), 238-248. doi: 10.1016/j.bbr.2009.06.026 URL
44	Pereira, M., & Morrell, J. I . ( 2010). The medial preoptic area is necessary for motivated choice of pup- over cocaine- associated environments by early postpartum rats. Neuroscience, 167( 2), 216-231. doi: 10.1016/j.neuroscience.2010.02.015 URL
45	Pereira, M., & Morrell, J. I . ( 2011). Functional mapping of the neural circuitry of rat maternal motivation: Effects of site-specific transient neural inactivation. Journal of Neuroendocrinology, 23( 11), 1020-1035. doi: 10.1111/j.1365-2826.2011.02200.x URL
46	Reisbick S., Rosenblatt J. S., & Mayer A. D . ( 1975). Decline of maternal behavior in the virgin and lactating rat. Journal of Comparative & Physiological Psychology, 89( 7), 722-732.
47	Riccio, A . ( 2010). Dynamic epigenetic regulation in neurons: Enzymes, stimuli and signaling pathways. Nature Neuroscience, 13( 11), 1330-1337. doi: 10.1038/nn.2671 URL
48	Romero-Fernandez W., Borroto-Escuela D. O., Agnati L. F., & Fuxe K . ( 2013). Evidence for the existence of dopamine D2-oxytocin receptor heteromers in the ventral and dorsal striatum with facilitatory receptor-receptor interactions. Molecular Psychiatry, 18( 8), 849-850. doi: 10.1038/mp.2012.103 URL
49	Root D. H., Melendez R. I., Zaborszky L., & Napier T. C . ( 2015). The ventral pallidum: Subregion-specific functional anatomy and roles in motivated behaviors. Progress in Neurobiology, 130, 29-70. doi: 10.1016/j.pneurobio.2015.03.005 URL
50	Rosenblatt, J. S . ( 1967). Nonhormonal basis of maternal behavior in the rat. Science, 156( 3781), 1512-1513. doi: 10.1126/science.156.3781.1512 URL
51	Rosenblatt, J. S., & Siegel, H. I . ( 1981). Factors governing the onset and maintenance of maternal behavior among nonprimate mammals. In D. J. Gubernick & P. H. Klopfer (Eds.), Parental care in mammals ( pp. 13-76). Boston, MA: Springer.
52	Sabihi S., Dong S. M., Durosko N. E., & Leuner B . ( 2014). Oxytocin in the medial prefrontal cortex regulates maternal care, maternal aggression and anxiety during the postpartum period. Frontiers in Behavioral Neuroscience, 8, 258.
53	Seifritz E., Esposito F., Neuhoff J. G., Lüthi A., Mustovic H., Dammann G.,.. Di Salle F . ( 2003). Differential sex-independent amygdala response to infant crying and laughing in parents versus nonparents. Biological Psychiatry, 54( 12), 1367-1375. doi: 10.1016/S0006-3223(03)00697-8 URL
54	Seip, K. M., & Morrell, J. I . ( 2009). Transient inactivation of the ventral tegmental area selectively disrupts the expression of conditioned place preference for pup- but not cocaine- paired contexts. Behavioral Neuroscience, 123( 6), 1325-1338. doi: 10.1037/a0017666 URL
55	Seip K. M., Pereira M., Wansaw M. P., Reiss J. I., Dziopa E. I., & Morrell J. I . ( 2008). Incentive salience of cocaine across the postpartum period of the female rat. Psychopharmacology, 199( 1), 119-130. doi: 10.1007/s00213-008-1140-9 URL
56	Sesack, S. R., & Grace, A. A . ( 2010). Cortico-basal ganglia reward network: Microcircuitry. Neuropsychopharmacology, 35( 1), 27-47. doi: 10.1038/npp.2009.93 URL
57	Stolzenberg, D. S., & Champagne, F. A . ( 2016). Hormonal and non-hormonal bases of maternal behavior: The role of experience and epigenetic mechanisms. Hormones and Behavior, 77, 204-210. doi: 10.1016/j.yhbeh.2015.07.005 URL
58	Strathearn, L . ( 2011). Maternal neglect: Oxytocin, dopamine and the neurobiology of attachment. Journal of Neuroendocrinology, 23( 11), 1054-1065. doi: 10.1111/j.1365-2826.2011.02228.x URL
59	Swain J. E., Tasgin E., Mayes L. C., Feldman R., Constable R. T., & Leckman J. F . ( 2008). Maternal brain response to own baby-cry is affected by cesarean section delivery. Journal of Child Psychology & Psychiatry, 49( 10), 1042-1052.
60	Tzschentke T. M . ( 2007). Measuring reward with the conditioned place preference (CPP) paradigm: Update of the last decade. Addiction Biology, 12( 3-4), 227-462. doi: 10.1111/adb.2007.12.issue-3-4 URL
61	Wansaw M. P., Pereira M., & Morrell J. I . ( 2008). Characterization of maternal motivation in the lactating rat: Contrasts between early and late postpartum responses. Hormones and Behavior, 54( 2), 294-301. doi: 10.1016/j.yhbeh.2008.03.005 URL
62	Wu Z., Autry A. E., Bergan J. F., Watabe-Uchida M., & Dulac C. G . ( 2014). Galanin neurons in the medial preoptic area govern parental behaviour. Nature, 509( 7500), 325-330. doi: 10.1038/nature13307 URL
63	Zha, X., & Xu, X. H . ( 2015). Dissecting the hypothalamic pathways that underlie innate behaviors. Neuroscience Bulletin, 31( 6), 629-648. doi: 10.1007/s12264-015-1564-2 URL

[1]	王勇丽, 葛胜男, Lancy Lantin Huang, 万勤, 卢海丹. 言语想象的神经机制[J]. 心理科学进展, 2023, 31(4): 608-621.
[2]	孔祥祯, 张凤翔, 蒲艺. 空间导航的脑网络基础和调控机制[J]. 心理科学进展, 2023, 31(3): 330-337.
[3]	张明霞, 李雨欣, 李瑾, 刘勋. 内外动机对青少年记忆的影响及其神经机制[J]. 心理科学进展, 2023, 31(1): 1-9.
[4]	王松雪, 程思, 蒋挺, 刘勋, 张明霞. 外在奖赏对陈述性记忆的影响[J]. 心理科学进展, 2023, 31(1): 78-86.
[5]	邓尧, 王梦梦, 饶恒毅. 风险决策研究中的仿真气球冒险任务[J]. 心理科学进展, 2022, 30(6): 1377-1392.
[6]	李亮, 李红. 人们为什么会羞怯：认知机制及神经基础[J]. 心理科学进展, 2022, 30(5): 1038-1049.
[7]	武晓菲, 肖风, 罗劲. 创造性认知重评在情绪调节中的迁移效应及其神经基础[J]. 心理科学进展, 2022, 30(3): 477-485.
[8]	章丽娜, 宣宾. 语言产生中词频效应老化的神经基础与时间进程[J]. 心理科学进展, 2022, 30(2): 333-342.
[9]	李何慧, 黄慧雅, 董琳, 罗跃嘉, 陶伍海. 发展性阅读障碍与小脑异常：小脑的功能和两者的因果关系[J]. 心理科学进展, 2022, 30(2): 343-353.
[10]	胡佳宝, 雷扬, 定险峰, 程晓荣, 范炤. 大众与个人审美品位的认知与神经机制[J]. 心理科学进展, 2022, 30(2): 354-364.
[11]	陈群林, 丁珂. 发散思维的序列位置效应：创新想法动态产生机制的新视角[J]. 心理科学进展, 2022, 30(11): 2507-2517.
[12]	黄建平, 许婧娴, 宛小昂. 联想学习对消费行为的影响：基于产品搜索经验的视角[J]. 心理科学进展, 2022, 30(11): 2414-2423.
[13]	王紫乐, 张琪. 视觉搜索中注意模板促进搜索的内在机制[J]. 心理科学进展, 2022, 30(10): 2206-2218.
[14]	柳王娟, 定险峰, 程晓荣, 范炤. 序列依赖效应——一种全新的“历史效应”[J]. 心理科学进展, 2022, 30(10): 2228-2239.
[15]	胡小勇, 杜棠艳, 李兰玉, 王甜甜. 低社会经济地位影响自我调节的神经机制[J]. 心理科学进展, 2022, 30(10): 2278-2290.