Limbic thalamic lesions, appetitively motivated discrimination learning, and training-induced neuronal activity in rabbits

Abstract

A substantial literature implicates the anterior and mediodorsal (limbic) thalamic nuclei and the reciprocally interconnected areas of cingulate cortex in learning, memory, and attentional processes. Previous studies have shown that limbic thalamic lesions severely impair discriminative avoidance learning and that they block development of training-induced neuronal activity in the cingulate cortex. The present study investigated the possibility that the limbic thalamus and cingulate cortex are involved in reward-based discriminative approach learning, wherein head-extension responses yielding oral contact with a drinking spout that was inserted into the conditioning chamber after a positive conditional stimulus (CS+) were reinforced with a water reward but responses to the spout after a negative conditional stimulus (CS-) were not reinforced. In this task, the rabbits learned primarily to omit their prepotent responses to the spout on CS- trials. Acquisition was severely impaired in rabbits given limbic thalamic lesions before training. As during avoidance learning, posterior cingulate cortical neurons of control rabbits developed learning-related neuronal responses to task-relevant stimuli, but this activity was severely attenuated in rabbits with lesions. These results support a general involvement of the cingulothalamic circuitry in instrumental approach and avoidance learning. The fact that learning consisted of response omission indicated that the cingulothalamic role is not limited to acquisition or production of active behavioral responses, such as locomotion. It is proposed that cingulothalamic neurons mediate associative attention, wherein enhanced neuronal responses to stimuli associated with reinforcement facilitate the selection and production of task-relevant responses.

Fig. 1.

Coronal sections showing the smallest (gray) and largest (white) lesions. Anterior cingulate cortical Area 24b and posterior cingulate cortical Area 29c/d recording sites are indicated byasterisks. Coordinates are shown in millimeters from bregma.

Fig. 2.

Percentage of spout contact responses made to the CS+ (solid lines) and the CS− (dashed lines) by control rabbits (gray lines) and rabbits with lesions (black lines). Because the rabbits took varying numbers of training sessions to attain the criterion, the data of several training stages common to all subjects are shown. For control rabbits, the seven stages included the first and last training sessions and five equally spaced sessions representing the second through the sixth training stages for each rabbit. Rabbits with lesions required approximately twice the number of training sessions to attain criterion than controls. The abscissalabels indicate the average session numbers used for each training stage. For example, if the second training stage comprised sessions 4, 5, 6, and 7, the average of the sessions used to obtain data for the second training stage would be 5.5.

Fig. 3.

Average integrated unit activity in the posterior cingulate cortex of control rabbits (top row) and rabbits with lesions (bottom row) during preliminary training and seven equally spaced training stages. Each plot shows the average integrated unit activity, in the form of Z-scores normalized to pre-CS baseline, from CS onset for 400 msec in 10 msec intervals with the response to the CS+ (black bars) and CS− (white bars). The numbers above each plot indicate the average of the ordinal numbers of the sessions that were averaged to obtain data for a given training stage. For example, if the second training stage comprised sessions 4, 5, 6, and 7, the average of the sessions used to obtain data for the second training stage would be 5.5.

Fig. 4.

Spike overlays of the neurons contributing to the long-latency multiple-unit records of four representative rabbits. Two of the records were recorded in control rabbits (A,B), and two were recorded in rabbits with lesions (C, D). Spikes are shown for early (A, C) and late (B,D) training sessions. Recording thresholds are indicated by horizontal lines.

Fig. 5.

Average multiunit spike frequency in the posterior cingulate cortex of control rabbits (top row) and rabbits with lesions (bottom row) at the beginning of training (Early) and at the end of training (Late). Each plot shows the average number of spikes per trial, in the form of Z-scores normalized to pre-CS baseline, from CS onset for 4.3 sec in 100 msec intervals with the response to the CS+ (black bars) and CS− (white bars). CS onset occurred at 0 sec, and CS− offset occurred at 0.5 sec. Spout presentation occurred 4 sec after CS onset and is indicated by anarrow.

Fig. 6.

Representative individual posterior cingulate cortical multiunit records from three control rabbits and three rabbits with lesions. Data are shown for early and late training sessions for each rabbit. Each plot shows the spike frequency, in the form of Z-scores normalized to pre-CS baseline, from CS onset to 4.3 sec after CS onset, in 100 msec intervals. The solid anddashed lines show the responses to the CS+ and CS−, respectively. CS onset occurred at 0 sec, and CS offset occurred at 0.5 sec. Spout presentation (arrow) occurred 4 sec after CS onset.

Fig. 7.

Average integrated unit activity in the anterior cingulate cortex of control rabbits (top row) and rabbits with lesions (bottom row) during preliminary training and seven equally spaced training stages. Each plot shows the average integrated unit activity, in the form of Z-scores normalized to pre-CS baseline, from CS onset for 400 msec in 10 msec intervals with the response to the CS+ (black bars) and CS− (white bars). Numbers above each plot indicate the average number of conditioning sessions represented by that stage. For example, if the second training stage comprised sessions 4, 5, 6, and 7, the average of the sessions used to obtain data for the second training stage would be 5.5.