Stimulus-related and movement-related single-unit activity in rabbit cingulate cortex and limbic thalamus during performance of discriminative avoidance behavior

A variety of studies have implicated the anterior cingulate cortex (ACC) in fear, including permanent storage of fear memory. Recent pharmacological and genetic studies indicate that early synaptic plasticity in the ACC may also contribute to certain forms of fear memory at early time points. However, no study has directly examined the possible changes in neuronal activity of ACC neurons in freely behaving mice during early learning. In the present study, we examined the neural responses of the ACC during trace fear conditioning. We found that ACC putative pyramidal and nonpyramidal neurons were involved in the termination of fear behavior ("un-freezing"), and the spike activity of these neurons was reduced during freezing. Some of the neurons were also found to acquire un-freezing locked activity and change their tuning. The results implicate the ACC neurons in fear learning and controlling the abolition of fear behavior. We also show that the ACC is important for making cue-related fear memory associations in the trace fear paradigm as measured with tone-evoked potentials and single-unit activity. Collectively, our findings indicate that the ACC is involved in predicting future aversive events and terminating fear during trace fear.

Section: Discussionmentioning

confidence: 99%

Predicting Aversive Events and Terminating Fear in the Mouse Anterior Cingulate Cortex during Trace Fear Conditioning

Steenland¹,

Li²,

Zhuo³

2012

“…Briefly, it is proposed that particular task-, and training stage-specific topographic distributions of brief latency CSϩ elicited cingulothalamic neuronal activity give rise to premotor "command volleys" in the cingulate cortex (Kubota et al, 1996), which are projected to striatal areas to trigger the output of the primed avoidance response.…”

Section: Discussionmentioning

confidence: 99%

“…With this approach it is possible to obtain a robust measure of localized learning-relevant neuronal activity, which remains stable over many days. Whereas the multiunit activity cannot document all relevant neuronal firing patterns, it has been shown to provide a reliable representation of the modal pattern of single-unit firing in these areas (Kubota et al, 1996).…”

Section: Methodsmentioning

confidence: 99%

Amygdalar Lesions Block Discriminative Avoidance Learning and Cingulothalamic Training-Induced Neuronal Plasticity in Rabbits

Poremba

Gabriel

1997

Self Cite

Learning to fear dangerous situations requires the participation of neurons of the amygdala. Here it is shown that amygdalar neurons are also involved in learning to avoid dangerous situations. Amygdalar lesions severely impaired the acquisition of acoustically cued, discriminative instrumental avoidance behavior of rabbits. In addition, the development of anterior cingulate cortical and medial dorsal thalamic training-induced neuronal plasticity in the early stages of behavioral acquisition was blocked in rabbits with lesions. The development of training-induced neuronal plasticity in the medial dorsal and anterior thalamic nuclei in late stages of behavioral acquisition was also blocked in rabbits with lesions. These results indicate that the integrity of the amygdala is essential for the establishment of both early and late training-induced cingulothalamic neuronal plasticity. It is hypothesized that amygdalar traininginduced neuronal plasticity in the initial trials of conditioning represents a substrate of learned fear, essential for the early and late cingulothalamic plasticity that is involved in mediation of acquisition of the instrumental avoidance response.Key words: limbic thalamus; cingulate cortex; amygdala; learning; operant conditioning; anterior ventral nucleus; medial dorsal nucleus Much information concerning the neural mediation of learned behavior has been provided by studies using the "model system" approach. These studies focus effort on the analysis of a single learning paradigm in a particular species (Carew et al., 1984;Steinmetz and Thompson, 1991;Gabriel, 1993). The present study continues an analysis of discriminative avoidance, wherein rabbits learn to step in an activity wheel in response to a tone that predicts foot shock, and they learn to ignore a different tone that does not predict foot shock.Past studies using lesions and multisite recording of neuronal activity have demonstrated that the cingulate cortex and the interconnected medial dorsal (MD) and anterior thalamic nuclei are essential for learning, and that neurons in these areas exhibit massive training-induced neuronal plasticity during learning (for review, see Gabriel, 1993). The thalamic training-induced neuronal plasticity does not depend on cerebral cortical afferents, because lesions in projecting cingulate cortical and hippocampal formation areas did not interfere with, indeed they enhanced, the development of the thalamic plasticity (Gabriel et al., 1987.Here, we tested the hypothesis that the integrity of the amygdala is essential for the development of training-induced plasticity in the anterior cingulate cortex and MD nucleus. This hypothesis was based on the following results: (1) the traininginduced plasticity of amygdalar, anterior cingulate cortical and MD thalamic neurons develops in parallel, in the early stages of learning; the plasticity in these areas diminishes as asymptotic levels of performance are attained (Applegate et al., 1982;Pascoe and Kapp, 1985;Nishijo et al., 1988;Gabriel, 1990;Maren et al...

“…Results of neuronal recording and lesion studies demonstrate a critical involvement of cingulate cortex and related limbic areas [the anterior and medial dorsal (MD) nuclei] of the thalamus in discriminative avoidance learning (for review, see Gabriel., 1993; see also Kubota et al, 1996). Intriguingly, cingulothalamic TIA and behavioral learning are blocked in rabbits with bilateral amygdalar lesions (Poremba and Gabriel, 1997), suggesting that amygdalar efferents are essential for the cingulothalamic TIA.…”

Section: Abstract: Limbic Thalamus; Cingulate Cortex; Amygdala; Learmentioning

confidence: 97%

Medial Geniculate Lesions Block Amygdalar and Cingulothalamic Learning-Related Neuronal Activity

Poremba

Gabriel

1997

Self Cite

This study assessed the role of the thalamic medial geniculate (MG) nucleus in discriminative avoidance learning, wherein rabbits acquire a locomotory response to a tone [conditioned stimulus (CS)ϩ] to avoid a foot shock, and they learn to ignore a different tone (CSϪ) not predictive of foot shock. Limbic (anterior and medial dorsal) thalamic, cingulate cortical, or amygdalar lesions severely impair acquisition, and neurons in these areas develop training-induced activity (TIA): more firing to the CSϩ than to the CSϪ. MG neurons exhibit TIA during learning and project to the amygdala. The MG neurons may supply afferents essential for amygdalar and cingulothalamic TIA and for avoidance learning. To test this hypothesis, bilateral electrolytic or excitotoxic ibotenic acid MG nuclear lesions were induced, and multiunit recording electrodes were chronically implanted into the anterior and posterior cingulate cortex, the anterior-ventral and medial-dorsal thalamic nuclei, and the basolateral nucleus of the amygdala before training. Learning was severely impaired and TIA was abolished in all areas in rabbits with lesions. Thus learning and TIA require the integrity of the MG nucleus. Only damage in the medial MG division was significantly correlated with the learning deficit. The lesions abolished the sensory response of amygdalar neurons, and they attenuated (but did not eliminate) the sensory response of cingulothalamic neurons, suggesting the existence of extra geniculate sources of auditory transmission to the cingulothalamic areas. Key words: limbic thalamus; cingulate cortex; amygdala; learning; instrumental conditioning; anterior ventral nucleus; medial dorsal nucleusThere is currently a great interest in the neural circuitry underlying aversively motivated learning (for review, see Davis, 1992;Gabriel, 1993;Lennartz and Weinberger, 1994;LeDoux, 1995;McGaugh et al., 1995;. A central role of amygdalar neurons is indicated by findings that amygdala lesions impair the acquisition of conditioned immobility (LeDoux et al., 1988; Fanselow and K im, 1994;LeDoux, 1995), autonomic responding (Blanchard and Blanchard, 1972;Spevack et al., 1975;Kapp et al., 1979;Gentile et al., 1986;Iwata et al., 1986;Helmstetter, 1992) and fear-potentiated startle behavior (Davis, 1986(Davis, , 1992Hitchcock and Davis, 1987;Sananes and Davis, 1992). Also, amygdalar neurons exhibit associative, training-induced activity (TIA) during Pavlovian conditioning (Umemoto and Olds, 1975;Applegate et al., 1982;Pascoe and Kapp, 1985;Nishijo et al., 1988; Muramoto et al., 1993;McEchron et al., 1995;Quirk et al., 1995).An involvement of the medial geniculate (MG) nucleus in aversively motivated learning is indicated by the observation of TIA in the medial division of the MG nucleus (MGm) (Olds et al., 1972;Gabriel et al., 1975;Gabriel et al., 1976;Ryugo and Weinberger, 1978;Birt and Olds, 1981;Weinberger, 1982;Edeline, 1990;Edeline and Weinberger, 1992;McEchron et al., 1995), and by impaired conditioning in animals with MG lesions (Iwata et al., 198...