Distinct behavioral phenotypes in novel "fast" kindling-susceptible and "slow" kindling-resistant rat strains selected by stimulation of the hippocampal perforant path.
Distinct behavioral phenotypes in novel "fast" kindling-susceptible and "slow" kindling-resistant rat strains selected by stimulation of the hippocampal perforant path.
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DOI：
10.1016/j.nbd.2015.10.008
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发表时间：
2016-01
影响因子：
6.1
通讯作者：
Sutula, Thomas P.
中科院分区：
文献类型：
--
作者：
Langberg, Tomer;Dashek, Ryan;Mulvey, Bernard;Miller, Kimberly A.;Osting, Susan;Stafstrom, Carl E.;Sutula, Thomas P.
关键词：
点燃是一种活动依赖的神经回路可塑性现象，由反复癫痫发作引起，导致癫痫易感性的进行性永久性增加。由于点燃引起的永久性结构和功能改变包括神经回路中不同范围的分子、细胞和功能变化，因此有兴趣确定与癫痫诱导可塑性相关的遗传背景是否也会影响其他行为基础神经回路的可塑性。选择近交系SD大鼠，饲养约15代，以“快”或“慢”的速度点燃发育，以响应刺激向海马区的穿支通路输入。经过7-8个世代的选择和选育，观察到了一致的“快”和“慢”点火率表型。第15代“快速”点燃大鼠(PPKS)至首次继发性全身性(V类)发作里程碑的点燃速率为10.7±1.1ADS，显著不同于需要25.5±2.0ADS的“慢”点燃PPKR大鼠和需要16.8±2.5ADS的杂交SD大鼠(P<；0.001，ANOVA)。对这一代癫痫幼稚的成年PPKs和PPKR大鼠与年龄匹配的成年杂交SD大鼠的后代进行了有效的行为测量比较，包括作为探索活动测量的开场测试，作为海马区空间记忆测量的Morris水迷宫，作为联合恐惧学习的行为范式的恐惧条件反射。对癫痫诱发的可塑性敏感性增加的PPKs(快速点燃)品系在旷场测试中运动探索活动显著增加，在Morris水迷宫中空间学习能力降低，但表现出正常的恐惧条件性学习，与近交系SD大鼠和耐“慢”点燃的PPKR品系相当。这些结果证实，基于对刺激激活的重复通路的反应的选择和育种可以产生对影响行为的遗传背景的持久修改。这些观察还表明，海马环路对癫痫诱导的可塑性的易感性或抵抗力的遗传背景也不同地影响依赖于点燃选择过程激活的环路的不同行为和学习，并可能与癫痫、共病行为状况和认知之间的联系有关。
Kindling is a phenomenon of activity-dependent neural circuit plasticity induced by repeated seizures that results in progressive permanent increases in susceptibility to epilepsy. As the permanent structural and functional modifications induced by kindling include a diverse range of molecular, cellular, and functional alterations in neural circuits, it is of interest to determine if genetic background associated with seizure-induced plasticity might also influence plasticity in neural circuitry underlying other behaviors. Outbred Sprague-Dawley (SD) rats were selected and bred for ~15 generations for “fast’ or “slow” rates of kindling development in response to stimulation of the perforant path input to the hippocampus. After 7-8 generations of selection and breeding, consistent phenotypes of “fast” and “slow” kindling rates were observed. By the 15th generation “fast” kindling rats referred to as Perforant Path Kindling Susceptible (PPKS) rats demonstrated a kindling rate of 10.7 ± 1.1 afterdischarges (ADs) to the milestone of the first secondary generalized (Class V) seizure, which differed significantly from “slow” kindling Perforant Path Kindling Resistant (PPKR) rats requiring 25.5 ± 2.0 ADs, and outbred SD rats requiring 16.8 ± 2.5 ADs (p < 0.001, ANOVA). Seizure-naïve adult PPKS and PPKR rats from offspring of this generation and age-matched adult outbred SD rats were compared in validated behavioral measures including the open field test as a measure of exploratory activity, the Morris water maze as a measure of hippocampal spatial memory, and fear conditioning as a behavioral paradigm of associative fear learning. The PPKS (“fast” kindling) strain with increased susceptibility to seizure-induced plasticity demonstrated statistically significant increases in motor exploratory activity in the open field test and reduced spatial learning the Morris water maze, but demonstrated normal fear conditioned learning comparable to outbred SD rats and the “slow” kindling-resistant PPKR strain. These results confirm that selection and breeding on the basis of responses to repeated pathway activation by stimulation can produce enduring modification of genetic background influencing behavior. These observations also suggest that genetic background underlying susceptibility or resistance to seizure-induced plasticity in hippocampal circuitry also differentially influences distinct behaviors and learning that depend on circuitry activated by the kindling selection process, and may have implications for associations between epilepsy, comorbid behavioral conditions, and cognition.
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影响因子：
5.3
作者：
GODDARD, GV;MCINTYRE, DC;LEECH, CK
通讯作者：
LEECH, CK
影响因子：
5.6
作者：
McIntyre, Dan C.;Gilby, Krista L.
通讯作者：
Gilby, Krista L.
影响因子：
3.4
作者：
Hannesson, DK;Howland, JG;Corcoran, ME
通讯作者：
Corcoran, ME
DOI：
10.1016/0013-4694(72)90177-0
发表时间：
1972-01-01
期刊：
ELECTROENCEPHALOGRAPHY AND CLINICAL NEUROPHYSIOLOGY
影响因子：
--
作者：
RACINE, RJ
通讯作者：
RACINE, RJ
影响因子：
3.3
作者：
Botterill, J. J.;Fournier, N. M.;Kalynchuk, L. E.
通讯作者：
Kalynchuk, L. E.