Lambe Evelyn K, Aghajanian George K
Department of Psychiatry, Yale School of Medicine, New Haven, CT 06519, USA.
Neuron. 2003 Sep 25;40(1):139-50. doi: 10.1016/s0896-6273(03)00598-1.
In vivo, thalamocortical axons are susceptible to the generation of terminal spikes which antidromically promote bursting in the thalamus. Although neurotransmitters could elicit such ectopic action potentials at thalamocortical boutons, this hypothesis has never been confirmed. Prefrontal cortex is the cortical area most implicated in arousal and is innervated by thalamic neurons that are unusual since they burst rhythmically during waking. We show that a neurotransmitter critical for alertness, hypocretin (orexin), directly excites prefrontal thalamocortical synapses in acute slice. This TTX-sensitive activation of thalamic axons was demonstrated electrophysiologically and by two-photon sampling of calcium transients at single spines in apposition to thalamic boutons anterogradely labeled in vivo. Spines receiving these long-range projections constituted a unique population in terms of the presynaptic excitatory action of hypocretin. By this mechanism, the hypocretin projection to prefrontal cortex may play a larger role in prefrontal or "executive" aspects of alertness and attention than previously anticipated.
在体内，丘脑皮质轴突易产生终末锋电位，该电位可逆向促进丘脑的爆发式放电。尽管神经递质可能在丘脑皮质终末引发这种异位动作电位，但这一假说从未得到证实。前额叶皮质是与觉醒关系最为密切的皮质区域，由丘脑神经元支配，这些丘脑神经元不同寻常，因为它们在清醒时会有节律地爆发式放电。我们发现，对警觉至关重要的神经递质——下丘脑分泌素（食欲素），可直接兴奋急性脑片中的前额叶丘脑皮质突触。这种对丘脑轴突的河豚毒素敏感激活通过电生理学方法以及对与体内顺行标记的丘脑终末相对的单个棘突处钙瞬变进行双光子采样得以证实。就下丘脑分泌素的突触前兴奋作用而言，接受这些长距离投射的棘突构成了一个独特的群体。通过这种机制，下丘脑分泌素向前额叶皮质的投射可能在警觉和注意力的前额叶或“执行”方面发挥比先前预期更大的作用。
