Ronesi Jennifer, Gerdeman Gregory L, Lovinger David M
Laboratory for Integrative Neuroscience, National Institute on Alcohol Abuse and Alcoholism, Rockville, Maryland 20852-0615, USA.
J Neurosci. 2004 Feb 18;24(7):1673-9. doi: 10.1523/JNEUROSCI.5214-03.2004.
Activation of the CB1 cannabinoid receptor inhibits neurotransmission at numerous synapses in the brain. Indeed, CB1 is essential for certain types of both short- and long-term synaptic depression. It was demonstrated recently that CB1 is critical for activity-dependent long-term depression (LTD) at glutamatergic corticostriatal synapses in acute brain slice preparations. Here, we show that CB1 activation is necessary, but not solely sufficient, for induction of LTD and that the requisite signaling by endocannabinoids (eCBs) occurs during a time window limited to the first few minutes after high-frequency stimulation delivery. In addition, we have applied intracellularly anandamide membrane transporter inhibitors to provide novel evidence that postsynaptic transport mechanisms are responsible for the release of eCBs from striatal medium spiny neurons. These findings shed new light on the mechanisms by which transient eCB formation participates in the induction of long-lasting changes in synaptic efficacy that could contribute to brain information storage.
CB1大麻素受体的激活会抑制大脑中众多突触处的神经传递。实际上，CB1对于某些类型的短期和长期突触抑制至关重要。最近有研究表明，在急性脑片制备中，CB1对于谷氨酸能皮质纹状体突触处的活动依赖性长期抑制（LTD）至关重要。在此，我们表明CB1激活对于LTD的诱导是必要的，但并非唯一充分条件，并且内源性大麻素（eCBs）的必要信号传导发生在高频刺激传递后的最初几分钟内的有限时间窗口内。此外，我们在细胞内应用了花生四烯酸乙醇胺膜转运体抑制剂，以提供新的证据，表明突触后转运机制负责从纹状体中型多棘神经元释放eCBs。这些发现为瞬时eCB形成参与诱导突触效能的持久变化从而可能有助于大脑信息存储的机制提供了新的线索。
