Local norepinephrine depletion and learning-related neuronal activity in cingulate cortex and anterior thalamus of rabbits.

Multi-unit neuronal activity was recorded in posterior cingulate cortex (area 29) and the anterior ventral (AV) thalamic nucleus during discriminative instrumental avoidance learning wherein a response (stepping in an activity wheel) to a 0.5-s tone (CS+) prevented a foot-shock 5 s after CS+ onset. Presentations of a different tone (CS-) on 50% of the conditioning trials in an irregular sequence with the CS+ did not predict shock and thus required no response. Two groups of rabbits received intracranial micro-injections of 6-hydroxydopamine (6-OHDA) to locally deplete the NE in area 29 or the AV nucleus. Vehicle was injected in the non-depleted area in each group and a third group received vehicle injections in both areas. Dopamine neurons in subjects that received 6-OHDA were protected by pre-treatment with GBR-12909. Neuronal data were collected during two pre-training sessions in response to the tones only and when the tones and shock were presented unpaired. Thalamically depleted rabbits made more, and cortically depleted rabbits made fewer, avoidance responses than controls during the early stages of behavioral acquisition, and cortically depleted rabbits made fewer responses than controls and thalamically depleted rabbits during extinction testing administered after the completion of acquisition. One effect of NE depletion on neuronal activity was entirely local: elimination of neuronal sensitization effects (enhanced discharges elicited by tones during the unpaired tone-shock pre-training treatment relative to pre-training with tones only). Other neuronal effects of NE depletion were system-wide, i.e., they occurred whether the depletion was cortical or thalamic.(ABSTRACT TRUNCATED AT 250 WORDS)