No abstract

Basolateral (BL) amygdaloid multi-unit activity was recorded as male albino rabbits learned to avoid a foot-shock unconditioned stimulus (US) by stepping in an activity wheel to an acoustic (pure tone) warning stimulus (CS+). A second tone (CS-) of different auditory frequency than the CS+ was presented in an irregular order on half of the conditioning trials but was never followed by the US. BL amygdaloid neurons developed, in the first session of conditioning, enhanced CS-elicited discharges relative to discharges recorded during pretraining with tones and noncontingent US presentations (excitatory plasticity), and greater discharges to the CS+ than to the CS- (discriminative plasticity). The discriminative plasticity attained maximal magnitude as the rabbits reached the asymptote of behavioral discrimination, and persisted during post-asymptotic training. Peak excitatory plasticity occurred in the session of the first significant behavioral discrimination and declined during the asymptotic and post-asymptotic stages of training. Similar patterns of excitatory and discriminative plasticity in structures directly interconnected with the BL nucleus (anterior cingulate cortex; medial dorsal thalamic nucleus) and effects of lesions suggest that the neurons in these areas participate in a circuit involved in mediation of avoidance learning.

Past studies of the neural determinants of discriminative avoidance conditioning in rabbits have fostered a theoretical model that describes the interactive functioning of the cingulate cortex (Brodmann's Areas 24 and 29), the anterior ventral and medial dorsal thalamic nuclei (AVN and MDN) and the hippocampus. Here we test hypotheses of the model concerning the influence of the hippocampus on cortical and thalamic information processing. The rabbits learned to perform locomotory conditioned responses (CRs) in an activity wheel in response to an acoustic (pure tone) positive conditional stimulus (CS+). A shock unconditional stimulus (US) was given 5 s after CS+ onset, but locomotion during the CS+ - US interval prevented the US. The rabbits also learned to ignore a second tone (a negative conditional stimulus, CS-) of different auditory frequency than the CS+, that did not predict the US. Multi-unit activity and intracranial macropotentials were recorded in the cingulate cortex and the AVN during acquisition, overtraining, extinction, reacquisition and reversal training. Data were obtained in intact rabbits and in rabbits with bilateral lesions of the subicular complex, the origin of projections of the hippocampal formation to the cingulate cortex and AVN. In addition, the activity in the AVN was recorded in a separate group of rabbits with posterior cingulate cortical (Area 29) lesions. Subicular and Area 29 lesions were associated with an enhancement of the training-induced CS+ elicited neuronal response in the AVN. The frequency of CRs was enhanced in animals with subicular lesions. CS elicited unit responses in the cingulate cortices were attenuated in rabbits with subicular lesions. Both of the lesions were associated with significantly increased amplitudes of the CS elicited average cortical and thalamic macropotentials. These results suggested the following conclusions: subiculocortical afferents provide an enabling influence that is essential for CS elicited excitation in the cingulate cortex; the cingulate cortical excitatory response in intact animals exerts a limiting influence on the activity in the AVN; the enhanced AVN neuronal response in rabbits with lesions is due to the absence of the limiting influence and it contributes to the increased CR frequency in those animals. It is hypothesized that the hippocampus via subiculocortical projections, governs the flow of CR-inducing thalamocortical excitatory volleys. This governance determines the timing of CR output. The results of hippocampal processing of contextual information acting through the subiculocortical projection determines the moment most appropriate for the CR.

Whereas the amygdala is generally understood to be involved in aversively motivated learning, the specific associative function of the amygdala remains controversial. This study addressed the amygdalar role in mediation of discriminative instrumental avoidance learning of rabbits. Bilateral microinjection of the GABA receptor agonist muscimol centered in the basolateral nucleus of the amygdala was given to inactivate amygdalar neurons at each of three stages of acquisition. The absence of behavioral learning in rabbits trained immediately after amygdalar inactivation confirmed previous results with electrolytic lesions. The absence of savings during training after muscimol had become ineffective indicated an amygdalar role in the establishment of acquisition-relevant neural plasticity, not simply in the expression of the learned response. A time-limited role of the amygdala in instrumental avoidance learning was indicated by the finding that intra-amygdalar muscimol failed to disrupt performance of the well-established avoidance response. The passage of time alone (with no training trials) was sufficient to reduce amygdalar involvement in response performance. These results and demonstrations that other limbic system areas make time-limited contributions to learning indicate that the amygdala is part of a larger intermediate memory system that supports learning and performance before habit consolidation.

It is well known that neurons of the medial geniculate (MG) nucleus of the thalamus send axonal projections to the amygdala. It has been proposed that these projections supply information that supports amygdalar associative processes underlying acquisition of acoustically cued conditioning and learning. Here we demonstrate the reverse direction of influence. Temporary inactivation of the amygdala using the GABA A receptor agonist muscimol just before the onset of discriminative avoidance conditioning permanently blocked the development of training-induced discriminative neuronal activity in the MG nucleus of rabbits. No discriminative activity developed when the amygdala was inactivated or during later training to criterion without muscimol. Thus, amygdalar processing at the outset of training is necessary for the development of training-induced discriminative activity of neurons in the MG nucleus.Key words: muscimol; GABA A agonist; temporary lesion; rabbits; associative conditioning; retention; multiunit neuronal activity It is well established that neurons in the amygdala and the medial geniculate (MG) nucleus, the auditory region of the sensory thalamus, are importantly involved in mediating acoustically cued Pavlovian and instrumental aversive conditioning Jarrell et al., 1986;LeDoux et al., 1986;McEchron et al., 1995;Maren and Fanselow, 1996;Davis, 1997; Poremba and Gabriel, 1997a,b;Armony et al., 1998;Ferry et al., 1999). Yet controversy remains as to the separate and distinct contributions of these nuclei, and little is known about how their neurons interact in mediating learning and performance.These issues could have been neatly resolved years ago had it been possible to confirm the hypothesis that neurons of the MG nucleus act simply to relay acoustic data to the amygdala via the direct axonal pathway documented by LeDoux et al. (1985). On this simple view, the function of MG nuclear neurons is sensory coding and transmission of acoustic signals. Interaction within the amygdala of the acoustic information with information concerning reinforcing stimuli would promote the development of plasticity at amygdalar synapses, which would thenceforth allow amygdalar neurons to respond uniquely to associatively significant acoustic cues, thus inducing the output of learned emotional responses and behaviors in other parts of the learning-relevant circuitry.A finding not easily incorporated into the foregoing model is the occurrence of training-induced associative neuronal activity, not simply sensory transmission, in the MG nucleus itself. For example, conditioning-induced, brief-latency discriminative neuronal activity develops in the medial region of the MG nucleus, and this activity exhibits reversal, during acquisition and reversal learning of a discriminative avoidance response (for review, see Gabriel et al., 1982). In the discriminative avoidance task, rabbits learn to avoid a foot shock by locomoting in response to a tone, the positive conditional stimulus (CSϩ), and they ignore a different tone, the CS...