Long-term potentiation in the accessory olfactory bulb: A mechanism for olfactory learning
Long-term potentiation in the accessory olfactory bulb: A mechanism for olfactory learning
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DOI：
10.1093/chemse/bjh158
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发表时间：
2005-01-01
期刊：
影响因子：
3.5
通讯作者：
Huang, GZ
中科院分区：
文献类型：
--
作者：
Kaba, H;Huang, GZ
嗅觉学习的一个背景已经被详细研究过，它涉及到交配时建立的记忆，以及雌鼠对交配雄鼠气味（信息素）的记忆。这种嗅觉记忆对于减轻可能由他的信息素引起的妊娠阻滞至关重要（Keverne和Rosser，1986）。来自一个陌生男性的信息素（尚未形成记忆）激活犁鼻系统，犁鼻器官中的受体，从而启动神经内分泌反射，抑制垂体分泌催乳素（Keverne，1983）。促黄体支持的去除导致孕酮水平下降并恢复发情。因此，已经假设信息素记忆用作抑制或调节特定信息素信号的门（Brennan等人，1990年; Kaba和Nakanishi，1995年; Brennan和Keverne，1997年; Brennan，2001年）。信息素记忆通过一次尝试学习获得，取决于交配并持续数周（Keverne和de la Riva，1982; Kaba等人，1988年）。作为记忆形成基础的神经变化发生在副嗅球（AOB）中，副嗅球是犁鼻系统中的第一中继，独立于主嗅觉系统和海马（Brennan等人，1990年; Kaba和Nakanishi，1995年; Brennan和Keverne，1997年）。AOB中的微电路包括二尖瓣细胞之间的显著的相互树突突触，一类投射神经元和颗粒细胞中间神经元。从二尖瓣细胞树突释放的谷氨酸激活颗粒细胞的树突，颗粒细胞的树突又介导GABA能树突状抑制回到二尖瓣细胞树突上（Jia et al.，1999年; Taniguchi和Kaba，2001年）。在相互突触处的这种反馈抑制调节二尖瓣细胞活性（Jia等人，1999年; Taniguchi和Kaba，2001年）。信息素记忆的形成需要信息素与AOB中的交配信号相关联。交配信号由蓝斑的去甲肾上腺素能投射传递。人工阴道宫颈刺激（Rosser和Keverne，1985）或交配（Brennan等人，1995）促进AOB中去甲肾上腺素（NA）的释放。交配后立即阻断AOB中的α-肾上腺素能受体可防止信息素记忆的形成（Kaba和Keverne，1988），交配前去除AOB的去甲肾上腺素能神经支配也是如此（Rosser和Keverne，1985）。此外，记忆形成与线粒体-颗粒细胞相互突触的神经化学和形态学变化相关（Brennan等人，1995; Matsuoka等人，1997年，2004年）。然而，尽管取得了这些进展，我们对电生理学方面的知识仍然存在一个重要的空白：突触强度的长期增加，称为长时程增强（LTP），几乎没有研究。此外，去甲肾上腺素能调节信息素学习的细胞和突触机制也是未知的。为了解决这些问题，我们在AOB切片中进行了一系列实验。
One context of olfactory learning that has been investigated in some detail concerns the memory, established at mating, and formed by the female mouse to the odours (pheromones) of the mating male. This olfactory memory is vital for mitigating pregnancy block that might otherwise be induced by his pheromones (Keverne and Rosser, 1986). Pheromones from an unfamiliar male, for which no memory has been formed, activate the vomeronasal system with their receptors in the vomeronasal organ, thereby initiating a neuroendocrine reflex that suppresses prolactin secretion from the pituitary (Keverne, 1983). The removal of luteotrophic support results in a fall in progesterone levels and a return to oestrus. Therefore, it has been hypothesized that the pheromonal memory functions as a gate to suppress or modulate the specific pheromonal signal (Brennan et al., 1990; Kaba and Nakanishi, 1995; Brennan and Keverne, 1997; Brennan, 2001). The pheromonal memory is acquired with one trial learning, depends upon mating and lasts for several weeks (Keverne and de la Riva, 1982; Kaba et al., 1988). The neural changes underlying memory formation occur in the accessory olfactory bulb (AOB), the first relay in the vomeronasal system, independently of the main olfactory system and the hippocampus (Brennan et al., 1990; Kaba and Nakanishi, 1995; Brennan and Keverne, 1997). Microcircuits in the AOB include the prominent reciprocal dendrodendritic synapse between mitral cells, a single class of projection neurons and granule cell interneurons. Glutamate released from mitral cell dendrites activates the dendrites of granule cells, which in turn mediate GABAergic dendrodendritic inhibition back onto mitral cell dendrites (Jia et al., 1999; Taniguchi and Kaba, 2001). This feedback inhibition at the reciprocal synapses regulates mitral cell activity (Jia et al., 1999; Taniguchi and Kaba, 2001). The formation of the pheromonal memory requires the association of the pheromonal and the mating signals in the AOB. The mating signal is conveyed by noradrenergic projections from the locus coeruleus. Artificial vaginocervical stimulation (Rosser and Keverne, 1985) or mating (Brennan et al., 1995) promotes the release of noradrenaline (NA) in the AOB. Blockade of α-adrenergic receptors in the AOB immediately after mating prevents the formation of the pheromonal memory (Kaba and Keverne, 1988), as does removal of noradrenergic innervation of the AOB prior to mating (Rosser and Keverne, 1985). Furthermore, memory formation is associated with neurochemical and morphological changes at the mitral–granule cell reciprocal synapses (Brennan et al., 1995; Matsuoka et al., 1997, 2004). Despite advances such as these, however, an important void in our knowledge of electrophysiological aspects has remained: a longlasting increase in synaptic strength, known as long-term potentiation (LTP), has been little investigated. Moreover, the cellular and synaptic mechanisms underlying noradrenergic modulation of pheromonal learning are also unknown. To address these questions, we have carried out a series of experiments in AOB slices.