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Towards an Understanding of the Contribution of Locus Coeruleus to Functional Networks and their Learning-Related Plasticity

Sebastien Bouret and Susan J. Sara
Neuromodulation and Memory Processes, CNRS, University Pierre & Marie Curie, Paris, France

We are attempting to relate activity in Locus Coeruleus (LC) to changes in spontaneous activity and evoked responses in two forebrain regions strongly implicated in cognitive processes: the medial Frontal Cortex (mFC) and the Basal Lateral Amygdala (BLA). We record single unity activity (SUA) simultaneously from LC and either mFC or BLA (in recent experiments, both).

mFC-LC recordings are made in freely moving rats engaged in a Go-NoGo odour discrimination task where stimulus-reinforcement contingencies were changed after each asymptotic performance, in order to study plasticity of neuronal responses in both regions along with the behavioural adaptation to the changed contingencies. LC responses are remarkably homogenous, responding initially to the light on-set signal and to primary reward, but not to odours. After several trials these cells began to respond to the odour associated with the reward, rather than to the reward, itself. The responses are related to "reward expectancy" in that they occur just before the behavioural response that elicits reward delivery. When stimulus-reward contingencies are modified, requiring new behavioural responses (extinction, reversal or intradimensional shift), LC neurons rapidly extinguish to the former CS+ and acquire the new association.

In contrast to LC, mFC responses are heterogeneous. Some cells respond to the light with sustained inhibition; 25% showed a phasic response during the 'reward expectancy' period; a few cells signal trial outcome as a function of behavioural response. The latency of mPFC responses within the trial, excitatory or inhibitory, is always longer than that seen in LC. Moreover, across trials during the learning of new reward contingencies, mPC responses appeared after the animal expressed behavioural learning, while LC cellular adaptation always preceded the behavioural expression of learning by many trials.

LC and BLA SUA were recorded in anesthetized rats subjected to contralateral pawshock. Neurons in LC responded homogeneously and vigorously with a short latency (~25ms) burst of excitation, inhibition, further excitation, followed by an extended period of inhibition (~ 1 sec). BLA responses were heterogenous even when single units were recorded from the same electrode tip. 2/3 responded to FS with either prolonged inhibition, or excitation as a phasic burst after the initial LC response, or a long-lasting excitation in phasic opposition to LC activity. Complementary experiments showed that 60% of BLA neurons are under potent inhibitory control of LC, as they respond to single-pulse stimulation of LC with prolonged inhibition.

Given the extent of the reciprocal connections between BLA and mFC and the important influence of LC on both regions, simultaneous recording from all three regions during learning should provide evidence that LC activation during specific phases of stimulus processing and learning promotes plasticity in learning-related forebrain networks.