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Supplemental Material for Cognitive and Arginine Metabolic Correlates of Temporal Dysfunction in the MIA Rat Model of Schizophrenia Risk MIA大鼠精神分裂症风险模型中认知和精氨酸代谢与颞功能障碍相关的补充材料
IF 1.9 4区 医学 Q3 BEHAVIORAL SCIENCES Pub Date : 2022-10-24 DOI: 10.1037/bne0000540.supp
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引用次数: 0
Behavioral and neurochemical effects of nociceptin/orphanin FQ receptor activation in the social defeat protocol. 社交失败方案中伤害肽/孤啡肽FQ受体激活的行为和神经化学效应。
IF 1.9 4区 医学 Q3 BEHAVIORAL SCIENCES Pub Date : 2022-10-24 DOI: 10.1037/bne0000539.supp
Alice Barros Câmara, Igor Augusto Brandão
The nociceptin/orphanin FQ receptor (NOP receptor) has wide expression in the nervous system and is involved in neurotransmitter release. However, the role of the NOPR in depression is not widely recognized. This study aims to evaluate behavioral and biochemical effects of the NOPR agonist Ro 65-6570 in mice submitted to social defeat protocol. The open-field test, social interaction test, and tail suspension test were applied to evaluate depressive behavior in male Swiss mice. Blood and brain tissue samples were obtained to evaluate the oxidative stress. The NOP agonist, Ro 65-6570 (1 mg/kg), or the social defeat stress reduced exploration rate in the open-field test. The social defeat stress and/or the NOP agonist also increased immobility time in the tail suspension test and the grooming time, as well as reduced the social interaction on the last day of social defeat protocol. Seven days after the end of the protocol, only the drug alone was able to affect the animals' interaction. Additionally, the NOP agonist increased the concentration of carbonyl groups (CGs) in hippocampus and malondialdehyde in serum. The stress of social defeat and the NOP agonist, together, increased malondialdehyde in animals' serum and prefrontal cortex, as well as increased the CGs concentration in the prefrontal cortex. These findings indicate a chronic depressive effect induced by the NOPR activation, sometimes regardless of the social defeat stress. We suggest that the NOPR signaling can activate pathways involved in cellular oxidative stress, contributing to the depression pathology. (PsycInfo Database Record (c) 2022 APA, all rights reserved).
伤害肽/孤啡肽FQ受体(NOP受体)在神经系统中广泛表达,并参与神经递质的释放。然而,NOPR在抑郁症中的作用并没有得到广泛的认识。本研究旨在评估NOPR激动剂Ro65-6570对接受社交失败方案的小鼠的行为和生化影响。采用开放场地试验、社会互动试验和尾部悬吊试验对雄性瑞士小鼠的抑郁行为进行评估。获得血液和脑组织样本以评估氧化应激。NOP激动剂Ro 65-6570(1 mg/kg)或社交失败应激降低了野外试验中的探索率。社交失败压力和/或NOP激动剂也增加了尾部悬吊测试中的不动时间和梳理时间,并减少了社交失败协议最后一天的社交互动。方案结束七天后,只有单独的药物能够影响动物的相互作用。此外,NOP激动剂增加了海马中羰基(CGs)的浓度和血清中丙二醛的浓度。社交失败的压力和NOP激动剂一起增加了动物血清和前额叶皮层中的丙二醛,并增加了前额叶皮层的CGs浓度。这些发现表明,NOPR激活会引起慢性抑郁效应,有时与社交失败压力无关。我们认为,NOPR信号可以激活参与细胞氧化应激的途径,从而促进抑郁症的病理学。(PsycInfo数据库记录(c)2022 APA,保留所有权利)。
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引用次数: 1
Sex and estrous cycle in memory for sequences of events in rats. 大鼠记忆中事件序列的性周期和发情周期。
IF 1.9 4区 医学 Q3 BEHAVIORAL SCIENCES Pub Date : 2022-10-01 Epub Date: 2022-03-07 DOI: 10.1037/bne0000508
M Jayachandran, P Langius, F Pazos Rego, R P Vertes, T A Allen

The ability to remember sequences of events is fundamental to episodic memory. While rodent studies have examined sex and estrous cycle in episodic-like spatial memory tasks, little is known about these biological variables in memory for sequences of events that depend on representations of temporal context. We investigated the role of sex and estrous cycle in rats during training and testing stages of a cross-species validated sequence memory task (Jayachandran et al., 2019). Rats were trained on a two four-odor sequence memory task delivered on opposite ends of a linear track. Training occurred in six successive stages starting with learning to poke in a nose-port for ≥ 1.2 s; eventually demonstrating sequence memory by holding their nose in the port ≥ 1 s for in-sequence odors and < 1 s for out-of-sequence odors. Performance was analyzed across sex and estrous cycle (proestrus, estrus, metestrus, and diestrus), the latter being determined by cellular composition of a daily vaginal lavage. We found no evidence of sex differences in asymptotic sequence memory performance, similar to humans performing an analogous task (Reeders et al., 2021). Likewise, no differences in sequence memory performance were found across the estrous cycle. Some caveats are that males acquired out-of-sequence trials faster during training with a 3-odor sequence, but this apparent advantage did not carry over to the 4-odor sequence. Additionally, males had shorter poke times overall which seem consistent with a decreased overall response inhibition because they occurred regardless of sequence demands. Together, these results suggest sex and estrous cycle are not major factors in sequence memory capacities. (PsycInfo Database Record (c) 2022 APA, all rights reserved).

记忆事件序列的能力是情节记忆的基础。虽然啮齿类动物的研究已经在类似情景的空间记忆任务中检查了性和发情周期,但对于依赖于时间上下文表征的事件序列的记忆中的这些生物变量知之甚少。我们研究了在跨物种验证序列记忆任务的训练和测试阶段,性和发情周期在大鼠中的作用(Jayachandran等人,2019)。大鼠接受了在线性轨道两端进行的两个四气味序列记忆任务的训练。训练分为六个连续阶段,从学习戳鼻孔开始,持续时间≥1.2秒;最终通过将鼻子保持在端口中来证明序列记忆,对于序列内气味≥1秒,对于序列外气味<1s。分析了性别和发情周期(发情前期、发情期、中期和发情期)的表现,后者由每日阴道灌洗的细胞组成决定。我们没有发现渐进序列记忆表现存在性别差异的证据,类似于人类执行类似任务(Reeders等人,2021)。同样,在整个发情周期中,没有发现序列记忆表现的差异。一些注意事项是,雄性在使用3气味序列的训练中更快地获得了序列外试验,但这种明显的优势并没有延续到4气味序列中。此外,雄性的戳戳时间总体较短,这似乎与总体反应抑制的降低一致,因为它们的发生与序列需求无关。总之,这些结果表明性和发情周期不是序列记忆能力的主要因素。(PsycInfo数据库记录(c)2022 APA,保留所有权利)。
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引用次数: 2
A limited cerebellar contribution to suprasecond timing across differing task demands. 小脑对跨不同任务要求的超秒计时的有限贡献。
IF 1.9 4区 医学 Q3 BEHAVIORAL SCIENCES Pub Date : 2022-10-01 DOI: 10.1037/bne0000531
Kelsey A Heslin, Jessica R Purnell, Benjamin J De Corte, Krystal L Parker

The involvement of the cerebellum in suprasecond interval timing (i.e., timing in the seconds to minutes range) is controversial. A limited amount of evidence from humans, nonhuman primates, and rodents has shown that the lateral cerebellum, including the lateral cerebellar nucleus (LCN), may be necessary for successful suprasecond timing performance. However, many existing studies have pitfalls, such as limited timing outcome measures and confounded task demands. In addition, many existing studies relied on well-trained subjects. This approach may be a drawback, as the cerebellum is hypothesized to carry out ongoing error correction to limit timing variability. By using only experienced subjects, past timing studies may have missed a critical window of cerebellar involvement. In the experiments described here, we pharmacologically inactivated the rat LCN across three different peak interval timing tasks. We structured our tasks to address past confounds, collect timing variability measures, and characterize performance during target duration acquisition. Across these various tasks, we did not find strong support for cerebellar involvement in suprasecond interval timing. Our findings support the existing distinction of the cerebellum as a subsecond interval timing brain region. (PsycInfo Database Record (c) 2022 APA, all rights reserved).

小脑参与超秒间隔计时(即秒到分钟范围内的计时)是有争议的。来自人类、非人类灵长类动物和啮齿动物的有限证据表明,外侧小脑,包括外侧小脑核(LCN),可能是成功的超秒计时性能所必需的。然而,许多现有的研究存在缺陷,如时间限制,结果测量和混淆的任务需求。此外,许多现有的研究依赖于训练有素的受试者。这种方法可能是一个缺点,因为假设小脑进行持续的错误纠正以限制时间变异性。由于只使用有经验的受试者,过去的时间研究可能错过了小脑参与的关键窗口。在这里描述的实验中,我们通过三种不同的峰间隔定时任务从药理学上灭活了大鼠LCN。我们组织了我们的任务,以解决过去的混乱,收集时间可变性测量,并在目标持续时间获取期间描述性能。在这些不同的任务中,我们没有发现小脑参与超秒间隔计时的有力支持。我们的发现支持小脑作为亚秒间隔计时脑区域的现有区别。(PsycInfo Database Record (c) 2022 APA,版权所有)。
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引用次数: 2
Neural population clocks: Encoding time in dynamic patterns of neural activity. 神经群体时钟:以神经活动的动态模式编码时间。
IF 1.6 4区 医学 Q3 BEHAVIORAL SCIENCES Pub Date : 2022-10-01 Epub Date: 2022-04-21 DOI: 10.1037/bne0000515
Shanglin Zhou, Dean V Buonomano

The ability to predict and prepare for near- and far-future events is among the most fundamental computations the brain performs. Because of the importance of time for prediction and sensorimotor processing, the brain has evolved multiple mechanisms to tell and encode time across scales ranging from microseconds to days and beyond. Converging experimental and computational data indicate that, on the scale of seconds, timing relies on diverse neural mechanisms distributed across different brain areas. Among the different encoding mechanisms on the scale of seconds, we distinguish between neural population clocks and ramping activity as distinct strategies to encode time. One instance of neural population clocks, neural sequences, represents in some ways an optimal and flexible dynamic regime for the encoding of time. Specifically, neural sequences comprise a high-dimensional representation that can be used by downstream areas to flexibly generate arbitrarily simple and complex output patterns using biologically plausible learning rules. We propose that high-level integration areas may use high-dimensional dynamics such as neural sequences to encode time, providing downstream areas information to build low-dimensional ramp-like activity that can drive movements and temporal expectation. (PsycInfo Database Record (c) 2022 APA, all rights reserved).

预测和准备近期和远期事件的能力是大脑执行的最基本的计算之一。由于时间对预测和感觉运动处理的重要性,大脑已经进化出了多种机制,可以在从微秒到几天甚至更长的时间范围内告诉和编码时间。汇集实验和计算数据表明,在秒的尺度上,时间依赖于分布在不同大脑区域的不同神经机制。在以秒为单位的不同编码机制中,我们将神经群体时钟和斜坡活动区分为不同的时间编码策略。神经群体时钟的一个例子,神经序列,在某些方面代表了时间编码的最佳和灵活的动态机制。具体而言,神经序列包括高维表示,下游区域可以使用该高维表示来使用生物学上合理的学习规则灵活地生成任意简单和复杂的输出模式。我们提出,高级集成区域可以使用高维动力学(如神经序列)来编码时间,为下游区域提供信息,以构建低维斜坡状活动,从而驱动运动和时间预期。(PsycInfo数据库记录(c)2022 APA,保留所有权利)。
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引用次数: 0
How do real animals account for the passage of time during associative learning? 在联想学习过程中,真实的动物是如何解释时间的流逝的?
IF 1.6 4区 医学 Q3 BEHAVIORAL SCIENCES Pub Date : 2022-10-01 Epub Date: 2022-04-28 DOI: 10.1037/bne0000516
Vijay Mohan K Namboodiri

Animals routinely learn to associate environmental stimuli and self-generated actions with their outcomes such as rewards. One of the most popular theoretical models of such learning is the reinforcement learning (RL) framework. The simplest form of RL, model-free RL, is widely applied to explain animal behavior in numerous neuroscientific studies. More complex RL versions assume that animals build and store an explicit model of the world in memory. To apply these approaches to explain animal behavior, typical neuroscientific RL models make implicit assumptions about how real animals represent the passage of time. In this perspective, I explicitly list these assumptions and show that they have several problematic implications. I hope that the explicit discussion of these problems encourages the field to seriously examine the assumptions underlying timing and reinforcement learning. (PsycInfo Database Record (c) 2022 APA, all rights reserved).

动物通常会学会将环境刺激和自我产生的行为与其结果(如奖励)联系起来。强化学习(RL)框架是这种学习最流行的理论模型之一。RL的最简单形式,无模型RL,在许多神经科学研究中被广泛应用于解释动物行为。更复杂的RL版本假设动物在记忆中构建并存储一个明确的世界模型。为了应用这些方法来解释动物的行为,典型的神经科学RL模型对真实动物如何代表时间的流逝做出了隐含的假设。从这个角度来看,我明确列出了这些假设,并表明它们有几个问题。我希望对这些问题的明确讨论能鼓励该领域认真研究时间和强化学习的基本假设。(PsycInfo数据库记录(c)2022 APA,保留所有权利)。
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引用次数: 0
Effects of a cue associated with cocaine or food reinforcers on extinction and postextinction return of behavior. 与可卡因或食物强化物相关的线索对灭绝和灭绝后行为恢复的影响。
IF 1.9 4区 医学 Q3 BEHAVIORAL SCIENCES Pub Date : 2022-08-01 DOI: 10.1037/bne0000519
David S Jacobs, Leah N Hitchcock, Rapheal G Williams, K Matthew Lattal

Studies of instrumental responding often include the delivery of a cue that is coincident with the delivery of the reinforcer. One purpose of this is for the cue to be removed during extinction and then presented later to assess whether responding returns (cue-induced reinstatement). In two experiments, we examined the effects of having a cue associated with reinforcement present or absent during extinction. In Experiment 1, the cue was associated with fixed ratio responding for intravenous cocaine or food pellets in one context (Context A), followed by extinction in another context (Context B), where responding produced the cue in one group but did not produce the cue in the other group. Afterward, contextual renewal was assessed with and without the cue in Context A. During extinction, a cue previously associated with cocaine reinforcement caused an increase in responding initially (an extinction burst) and throughout 16 2-hr extinction sessions, as well as weakened contextual renewal when animals were tested with the cue in Context A. In contrast, there were few detectable effects of the cue on extinction and contextual renewal when food pellets were the reinforcer. In Experiment 2, effects of a cue during extinction of progressive ratio responding were revealed with food pellets when animals showed weakened responding on the initial trials of postextinction reacquisition sessions. These experiments demonstrate that the presence of a cue associated with reinforcement during extinction may prolong responding in the short term while creating a more persistent form of extinction that resists relapse. (PsycInfo Database Record (c) 2022 APA, all rights reserved).

工具性反应的研究通常包括提示的传递与强化物的传递是一致的。这样做的一个目的是在消失过程中删除提示,然后稍后呈现以评估是否有响应返回(提示诱导恢复)。在两个实验中,我们检查了在消失过程中存在或不存在与强化相关的线索的影响。在实验1中,线索在一个情境(情境A)中与静脉注射可卡因或食物颗粒的固定比例反应相关,随后在另一个情境(情境B)中消失,其中一组的反应产生线索,而另一组不产生线索。在灭绝期间,先前与可卡因强化相关的线索在最初(灭绝爆发)和16个2小时的灭绝过程中引起了反应的增加,并且当动物在背景a中使用线索进行测试时,背景更新被削弱。相比之下,当食物颗粒作为强化物时,线索对灭绝和背景更新的影响几乎没有可检测到的。在实验2中,当动物在灭绝后再习得的初始试验中表现出较弱的反应时,食物颗粒提示对递进比反应消失的影响。这些实验表明,在消退过程中与强化相关的线索的存在可能会在短期内延长反应,同时创造一种更持久的消退形式,以抵抗复发。(PsycInfo Database Record (c) 2022 APA,版权所有)。
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引用次数: 2
Hormonal contraceptives alter amphetamine place preference and responsivity in the intact female rat. 激素避孕药改变安非他明在完整雌性大鼠的位置偏好和反应性。
IF 1.9 4区 医学 Q3 BEHAVIORAL SCIENCES Pub Date : 2022-08-01 DOI: 10.1037/bne0000520
Emily N Hilz, Marcelle E Olvera, Dohyun Jun, Megha Chadha, Ross Gillette, Marie-H Monfils, Andrea C Gore, Hongjoo J Lee

Hormonal contraceptives (HCs) containing synthetic ovarian hormones are commonly used among reproductive aged women; HCs alter the physiological state of the user by interfering with endogenous hormone concentrations and their actions on the reproductive tract. As ovarian hormones modulate the incidence of substance abuse disorders in women, this experiment explores how modulating female rat ovarian hormonal states with an HC containing the synthetic progestin levonorgestrel influences measures of drug preference and responsivity. First, rats underwent food-light Pavlovian conditioning to measure conditioned orienting, a known predictor of amphetamine (AMP) place preference. Then, rats were conditioned and tested for AMP place preference with either an HC implant or during estrous cycle stages associated with opposing ovarian hormone levels, that is, proestrus (P) or metestrus/diestrus (M/D), while recording ultrasonic vocalizations (USVs) as an index of he donic drug responsivity. Because of dopamine's (DA's) role in reward learning and memory, DA cell number and activity were examined using tyrosine hydroxylase and FOS immunohistochemistry after a final AMP challenge. Conditioned orienting did not differ between cycling and HC-implanted rats. HC rats emitted fewer USVs in response to AMP, showed marginally less AMP place preference, and had lower DA cell activity in the substantia nigra after AMP compared to P rats. M/D rats showed a similar behavioral profile and neural response as HC rats. This experiment suggests ovarian hormones affect drug preference and responsivity, while providing novel insight into how hormone-altering contraceptives may reduce these measures. (PsycInfo Database Record (c) 2022 APA, all rights reserved).

含有合成卵巢激素的激素避孕药(HCs)通常用于育龄妇女;HCs通过干扰内源性激素浓度及其对生殖道的作用来改变使用者的生理状态。由于卵巢激素调节女性药物滥用障碍的发生率,本实验探讨了含有合成孕激素左炔诺孕酮的HC如何调节雌性大鼠卵巢激素状态影响药物偏好和反应性的测量。首先,大鼠接受了食物轻的巴甫洛夫条件反射来测量条件定向,这是一种已知的安非他明(AMP)位置偏好的预测因子。然后,用HC植入大鼠或在与卵巢激素水平相反的发情周期阶段(即发情前期(P)或初潮/初潮(M/D))对大鼠进行AMP位置偏好的条件反射和测试,同时记录超声发声(USVs)作为药物反应性的指标。由于多巴胺(DA)在奖励学习和记忆中的作用,在最后一次AMP刺激后,使用酪氨酸羟化酶和FOS免疫组织化学检测DA细胞的数量和活性。条件定向在循环大鼠和hc植入大鼠之间没有差异。与P大鼠相比,HC大鼠对AMP的反应释放出更少的usv, AMP的位置偏好略低,AMP后黑质DA细胞活性较低。M/D大鼠表现出与HC大鼠相似的行为特征和神经反应。该实验表明卵巢激素影响药物偏好和反应性,同时为改变激素的避孕药如何减少这些措施提供了新的见解。(PsycInfo Database Record (c) 2022 APA,版权所有)。
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引用次数: 1
Surprise-induced enhancements in the associability of Pavlovian cues facilitate learning across behavior systems. 惊喜引起的巴甫洛夫线索联想性的增强促进了跨行为系统的学习。
IF 1.9 4区 医学 Q3 BEHAVIORAL SCIENCES Pub Date : 2022-08-01 DOI: 10.1037/bne0000505
Inmaculada Márquez, Gabriel Loewinger, Juan Pedro Vargas, Juan Carlos López, Estrella Díaz, Guillem R Esber

Surprising violations of outcome expectancies have long been known to enhance the associability of Pavlovian cues; that is, the rate at which the cue enters into further associations. The adaptive value of such enhancements resides in promoting new learning in the face of uncertainty. However, it is unclear whether associability enhancements reflect increased associative plasticity within a particular behavior system, or whether they can facilitate learning between a cue and any arbitrary outcome, as suggested by attentional models of conditioning. Here, we show evidence consistent with the latter hypothesis. Violating the outcome expectancies generated by a cue in an appetitive setting (feeding behavior system) facilitated subsequent learning about the cue in an aversive setting (defense behavior system). In addition to shedding light on the nature of associability enhancements, our findings offer the neuroscientist a behavioral tool to dissociate their neural substrates from those of other, behavior system- or valence-specific changes. Moreover, our results present an opportunity to utilize associability enhancements to the advantage of counterconditioning procedures in therapeutic contexts. (PsycInfo Database Record (c) 2022 APA, all rights reserved).

人们早就知道出人意料地违反结果预期会增强巴甫洛夫线索的联想性;也就是说,线索进入进一步联想的速度。这种增强的适应价值在于在面对不确定性时促进新的学习。然而,目前尚不清楚联想性增强是否反映了特定行为系统中联想可塑性的增加,或者它们是否可以促进线索和任意结果之间的学习,正如条件作用的注意模型所表明的那样。在这里,我们展示了与后一种假设一致的证据。违反食欲环境(进食行为系统)中线索产生的结果预期,促进了随后在厌恶环境(防御行为系统)中对线索的学习。除了揭示联想性增强的本质,我们的发现还为神经科学家提供了一种行为工具,将他们的神经基质与其他行为系统或价特异性变化的神经基质分离开来。此外,我们的结果提供了一个机会,利用联想性增强的优势,在治疗背景下对抗条件作用程序。(PsycInfo Database Record (c) 2022 APA,版权所有)。
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引用次数: 0
Time to contrast models of timing: The structure of temporal memory. 时间与时间模型的对比:时间记忆的结构。
IF 1.9 4区 医学 Q3 BEHAVIORAL SCIENCES Pub Date : 2022-06-02 DOI: 10.1037/bne0000521
A. Machado, Marilia Pinheiro de Carvalho, Marco Vasconcelos
In the study of animal timing over the last 100 years, we identify three different periods, each characterized by a distinct activity. In the first period, researchers brought timing into the laboratory and explored its multiple expressions empirically. In the second period, the growing body of empirical findings inspired researchers to develop a plethora of timing models that vary in theoretical orientation, scope, depth, and quantitative explicitness. We argue that it is now the time to advance towards a third period, wherein researchers select models by comparing them with one another and with data. We make our case by contrasting how the scalar expectancy theory and the learning-to-time model conceive of temporal memory and learning both in concurrent timing tasks and in retrospective timing tasks. We identify four problems related to the structure of temporal memory and to the rules of temporal learning that challenge these models and that should drive the next steps in modeling the timing abilities of animals. (PsycInfo Database Record (c) 2022 APA, all rights reserved).
在对过去100年动物时间的研究中,我们确定了三个不同的时期,每个时期都有一个不同的活动特征。第一个阶段,研究者将时间引入实验室,并从实证角度探索其多重表现形式。在第二个时期,越来越多的实证研究结果激发了研究人员开发了大量的时间模型,这些模型在理论取向、范围、深度和定量清晰度方面各不相同。我们认为,现在是时候向第三个阶段迈进了,在这个阶段,研究人员通过相互比较和与数据比较来选择模型。我们通过对比标量期望理论和学习-时间模型如何理解并发计时任务和回顾性计时任务中的时间记忆和学习来证明我们的观点。我们确定了与时间记忆结构和时间学习规则相关的四个问题,这些问题挑战了这些模型,并且应该推动动物计时能力建模的下一步。(PsycInfo Database Record (c) 2022 APA,版权所有)。
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引用次数: 1
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Behavioral neuroscience
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