Song Chenghui, Ehlers Vanessa L, Moyer James R
Departments of Psychology and.
Departments of Psychology and Biological Sciences, University of Wisconsin-Milwaukee, Milwaukee, Wisconsin 53201
J Neurosci. 2015 Sep 30;35(39):13511-24. doi: 10.1523/JNEUROSCI.2329-15.2015.
Neuronal activity in medial prefrontal cortex (mPFC) is critical for the formation of trace fear memory, yet the cellular mechanisms underlying these memories remain unclear. One possibility involves the modulation of intrinsic excitability within mPFC neurons that project to the basolateral complex of amygdala (BLA). The current study used a combination of retrograde labeling and in vitro whole-cell patch-clamp recordings to examine the effect of trace fear conditioning on the intrinsic excitability of layer 5 mPFC-BLA projection neurons in adult rats. Trace fear conditioning significantly enhanced the intrinsic excitability of regular spiking infralimbic (IL) projection neurons, as evidenced by an increase in the number of action potentials after current injection. These changes were also associated with a reduction in spike threshold and an increase in h current. In contrast, trace fear conditioning reduced the excitability of regular spiking prelimbic (PL) projection neurons, through a learning-related decrease of input resistance. Interestingly, the amount of conditioned freezing was (1) positively correlated with excitability of IL-BLA projection neurons after conditioning and (2) negatively correlated with excitability of PL-BLA projection neurons after extinction. Trace fear conditioning also significantly enhanced the excitability of burst spiking PL-BLA projection neurons. In both regions, conditioning-induced plasticity was learning specific (observed in conditioned but not in pseudoconditioned rats), flexible (reversed by extinction), and transient (lasted <10 d). Together, these data suggest that intrinsic plasticity within mPFC-BLA projection neurons occurs in a subregion- and cell-type-specific manner during acquisition, consolidation, and extinction of trace fear conditioning. Significance statement: Frontal lobe-related function is vital for a variety of important behaviors, some of which decline during aging. This study involves a novel combination of electrophysiological recordings from fluorescently labeled mPFC-to-amygdala projection neurons in rats with acquisition and extinction of trace fear conditioning to determine how specific neurons change during behavior. This is the first study to demonstrate that trace fear conditioning significantly alters the intrinsic excitability of mPFC-to-amygdala projection neurons in a subregion- and cell-type-specific manner, which is also transient and reversed by extinction. These data are of broad interest to the neuroscientific community, and the results will inspire additional studies investigating the cellular mechanisms underlying circuit-specific changes within the brain as a result of associative learning and memory.
内侧前额叶皮质（mPFC）中的神经元活动对于痕迹恐惧记忆的形成至关重要，然而这些记忆背后的细胞机制仍不清楚。一种可能性涉及对投射到杏仁核基底外侧复合体（BLA）的mPFC神经元内在兴奋性的调节。当前研究结合逆行标记和体外全细胞膜片钳记录，以检查痕迹恐惧条件反射对成年大鼠5层mPFC - BLA投射神经元内在兴奋性的影响。痕迹恐惧条件反射显著增强了规则发放的边缘下区（IL）投射神经元的内在兴奋性，电流注入后动作电位数量增加证明了这一点。这些变化还与动作电位阈值降低和h电流增加有关。相反，痕迹恐惧条件反射通过与学习相关的输入电阻降低，降低了规则发放的前额叶前部（PL）投射神经元的兴奋性。有趣的是，条件性僵住的程度（1）与条件反射后IL - BLA投射神经元的兴奋性呈正相关，（2）与消退后PL - BLA投射神经元的兴奋性呈负相关。痕迹恐惧条件反射还显著增强了爆发式发放的PL - BLA投射神经元的兴奋性。在这两个区域，条件反射诱导的可塑性都是学习特异性的（在条件反射大鼠中观察到，而在假条件反射大鼠中未观察到）、灵活的（通过消退逆转）和短暂的（持续时间<10天）。总之，这些数据表明，在痕迹恐惧条件反射的获得、巩固和消退过程中，mPFC - BLA投射神经元内的内在可塑性以亚区域和细胞类型特异性的方式发生。意义声明：额叶相关功能对于多种重要行为至关重要，其中一些行为在衰老过程中会下降。本研究将大鼠中荧光标记的mPFC到杏仁核投射神经元的电生理记录与痕迹恐惧条件反射的获得和消退进行了新颖的结合，以确定特定神经元在行为过程中如何变化。这是第一项证明痕迹恐惧条件反射以亚区域和细胞类型特异性的方式显著改变mPFC到杏仁核投射神经元内在兴奋性的研究，这种改变也是短暂的且可通过消退逆转。这些数据引起了神经科学界的广泛关注，其结果将激发更多研究来探究大脑中因联想学习和记忆导致的特定回路变化背后的细胞机制。
