Impaired acquisition of a passive avoidance response after lesions induced in the locus coeruleus by 6-OH-dopamine

Abstract

CROW¹ and Kety² have advanced the hypothesis that the fine network of noradrenaline-containing nerve terminals which innervates the cerebral cortex³ is a necessary component of the mechanism of learning. In particular, it is suggested that these neurones deliver a “results of action”⁴ signal which registers the successful outcome of a particular behavioural sequence. The noradrenaline released in the cortex is believed to interact with a transient synaptic change resulting from recent neural activity (the ‘short-term trace’), to initiate the long term synaptic changes presumed to underlie learning. Various authors have suggested the existence of such a “confirming reaction”⁵, “results of action”⁴, or “now print”⁶ mechanism. The diffuse distribution of noradrenergic terminals in the cerebral cortex would allow this system to deliver a generalised message of the type required. Ungerstedt⁷ has demonstrated histochemically that the cortical noradrenergic terminals originate from cell bodies of the nucleus locus coeruleus in the dorsal pontine tegmentum, and this has been confirmed in biochemical studies^8,9. The concept of the coerulo-cortical noradrenergic system as a reinforcement pathway is supported by the observation that rats with electrodes in the region of the locus coeruleus can be trained to self stimulate^10,11 and this behaviour is accompanied by increased noradrenaline turnover in the ipsilateral cortex¹².