Hugues Sandrine, Kessal Karima, Hunt Mark J, Garcia Rene
Neurobiologie Comportementale, Equipe Avenir, Institut National de la Santé et de la Recherche Médicale, Université de Nice-Sophia Antipolis, 06108 Nice, France.
J Neurophysiol. 2003 Nov;90(5):3224-31. doi: 10.1152/jn.00895.2002.
Stress-related alterations to the induction of hippocampal synaptic plasticity have been implicated in certain forms of psychiatric disorders. However, relatively little is known about such changes in other psychiatric disorders-related structures. We tested this possibility in one of such structures, the nucleus accumbens, during re-exposure of rats to a conditioned stressful environment, in which they had previously received shock. In both control rats (no shock) and shocked rats previously submitted to an extensive pre-exposure to the to-be-conditioned contextual cues (latent inhibition), high- and low-frequency stimulation of fimbria-accumbens pathway induced, in the nucleus accumbens, similar pattern of increases and decreases in synaptic efficacy, respectively. However, in non-pre-exposed shocked rats, re-exposure to the conditioned contextual cues evoked high levels of freezing, which was accompanied by a blockade of the induction of enhancement, but a facilitation of the depression, of synaptic efficacy. In addition, contextual conditioning did not alter the baseline transmission whatever the stimulus intensity and was ineffective on the induction of fimbria-accumbens synaptic plasticity following complete extinction of freezing response to the conditioned contextual cues. These data support the idea according to which stress may be involved in certain forms of psychiatric disorders via induction of metaplastic changes in circuits including the hippocampus and hippocampal limbic target structures such as the nucleus accumbens.
应激相关的海马突触可塑性诱导改变与某些形式的精神疾病有关。然而,对于其他与精神疾病相关结构中的此类变化知之甚少。我们在大鼠重新暴露于先前曾遭受电击的条件性应激环境期间,在其中一个这样的结构——伏隔核中测试了这种可能性。在对照大鼠(无电击)和先前已广泛预先暴露于待条件化情境线索(潜伏抑制)的电击大鼠中,海马伞 - 伏隔核通路的高频和低频刺激分别在伏隔核中诱导出相似的突触效能增减模式。然而,在未预先暴露的电击大鼠中,重新暴露于条件性情境线索会引发高水平的僵住反应,这伴随着突触效能增强诱导的阻断,但突触效能降低的促进。此外,无论刺激强度如何,情境条件化均未改变基线传递,并且在对条件性情境线索的僵住反应完全消退后,对海马伞 - 伏隔核突触可塑性的诱导无效。这些数据支持这样一种观点,即应激可能通过诱导包括海马和海马边缘靶结构(如伏隔核)在内的神经回路中的元可塑性变化,参与某些形式的精神疾病。