Elsevier

Neuroscience

Volume 93, Issue 4, August 1999, Pages 1271-1287
Neuroscience

Emotional and behavioral correlates of the anterior cingulate cortex during associative learning in rats

https://doi.org/10.1016/S0306-4522(99)00216-XGet rights and content

Abstract

Neuronal activity was recorded from the anterior cingulate cortex of behaving rats during discrimination and learning of conditioned stimuli associated with or without reinforcements. The rats were trained to lick a protruding spout just after a conditioned stimulus to obtain reward (intracranial self-stimulation or sucrose solution) or to avoid aversion. The conditioned stimuli included both elemental (auditory or visual stimuli) and configural (simultaneous presentation of auditory and visual stimuli predicting reward outcome opposite to that predicted by each stimulus presented alone) stimuli. Of the 62 anterior cingulate neurons responding during the task, 38 and four responded differentially and non-differentially to the conditioned stimuli (conditioned stimulus-related neurons), respectively. Of the 38 differential conditioned stimulus-related neurons, 33 displayed excitatory (n=10) and inhibitory (n=23) responses selectively to the conditioned stimuli predicting reward. These excitatory and inhibitory differential conditioned stimulus-related neurons were located mainly in the cingulate cortex areas 1 and 3 of the rostral and ventral parts of the anterior cingulate cortex, respectively. The remaining 20 neurons responded mainly during intracranial self-stimulation and/or ingestion of sucrose (ingestion/intracranial self-stimulation-related neurons). Increase in activity of the ingestion/intracranial self-stimulation-related neurons was correlated to the first lick to obtain rewards during the task, suggesting that the activity reflected some aspects of motor functions for learned instrumental behaviors. These ingestion/intracranial self-stimulation-related neurons were located sparsely in cingulate cortex area 1 of the rostral part of the anterior cingulate cortex and densely in frontal area 2 of the caudal and dorsal parts of the anterior cingulate cortex. Analysis by the multidimensional scaling of responses of 38 differential conditioned stimulus-related neurons indicated that the anterior cingulate cortex categorized the conditioned stimuli into three groups based on reward contingency, regardless of the physical characteristics of the stimuli, in a two-dimensional space; the three conditioned (two elemental and one configural) stimuli predicting sucrose solution, the three conditioned (two elemental and one configural) stimuli predicting no reward, and the lone conditioned stimulus predicting intracranial self-stimulation.

The results suggest that the anterior cingulate cortex is organized topographically; stimulus attributes predicting reward or no reward are represented in the rostral and ventral parts of the anterior cingulate cortex, while the caudal and dorsal parts of the anterior cingulate cortex are related to execution of learned instrumental behaviors. These results are in line with recent neuropsychological studies suggesting that the rostral part of the anterior cingulate cortex plays a crucial role in socio-emotional behaviors by assigning a positive or negative value to future outcomes.

Section snippets

Subjects and experimental design

Nine male albino Wistar rats weighing 270–330 g (SLC, Hamamatsu, Japan) were used. The housing area was temperature controlled at 23°C and maintained on a 12-h/12-h light–dark cycle. Rats were placed on the water-deprivation regimen (see “Training” section). A rat was painlessly placed in the special stereotaxic apparatus with a device for sensory stimuli (Fig. 1A). Sensory stimuli included auditory (300-, 530-, 1200- and 2860-Hz tone), visual (white light) and configural (simultaneous

Classification of the anterior cingulate neurons

Over a period of one to three months for each rat, recordings were made from 418 neurons in and around the anterior cingulate cortex during the conditioning tasks. Of these, 321 neurons were located in the anterior cingulate cortex, and all 321 neurons were tested with at least the reward task. Of these 321 anterior cingulate neurons, 62 (19.3%; 62/321) responded (excitatory or inhibitory) in one or more phases of the task. These 62 responsive neurons were classified into two types in terms of

Spontaneous firing rates and latencies of rat anterior cingulate neurons

Spontaneous firing rates of anterior cingulate neurons in awake rabbits ranged from 1 to 17 spikes/s,25 which were comparable to those of the rat anterior cingulate neurons in the present study. In the present study, the differential conditioned stimulus-related neurons tended to have longer latencies than those of non-differential conditioned stimulus-related neurons. Previously, we reported a similar trend in the monkey amygdala,49., 50. the monkey septal nuclei,35 the monkey hippocampal

Conclusions

In the present study, anterior cingulate cortex neurons were classified into two categories based on the neuronal responses during each task phase: conditioned stimulus-related and ingestion/ICSS-related neurons. Analysis by MDS of differential conditioned stimulus-related neurons categorized the conditioned stimuli into three groups based on reward contingency, regardless of the physical characteristics of the stimuli in a two-dimensional space: the three conditioned stimuli (two elemental and

Acknowledgements

We thank Dr P. S. Grigson (The Pennsylvania State University) and Dr P. Martin (Toyama Medical and Pharmaceutical University) for help in preparing this manuscript. This work was supported partly by Japanese Ministry of Education, Science and Culture Grants-in-Aid for Scientific Research (11308033, 08279105, 10680762, 11145217), and by Funds for Comprehensive Research on Aging and Health.

References (85)

  • Y Kubota et al.

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

    Brain Res.

    (1996)
  • B Levin et al.

    Childhood obsessive–compulsive disorder and cingulate epilepsy

    Biol. Psychiat.

    (1991)
  • K Muramoto et al.

    Rat amygdaloid neuron responses during auditory discrimination

    Neuroscience

    (1993)
  • H Niki et al.

    Cingulate unit activity and delayed response

    Brain Res.

    (1976)
  • H Niki et al.

    Prefrontal and cingulate unit activity during timing behavior in the monkey

    Brain Res.

    (1979)
  • H Nishijo et al.

    Single neuron responses in the monkey anterior cingulate cortex during visual discrimination

    Neurosci. Lett.

    (1997)
  • T Ono et al.

    Integrated lateral hypothalamic neural responses to natural and artificial rewards and cue signals in the rat

    Brain Res.

    (1985)
  • E Orona et al.

    Multiple-unit activity of the prefrontal cortex and mediodorsal thalamic nucleus during acquisition of discriminative avoidance behavior in rabbits

    Brain Res.

    (1983)
  • E Orona et al.

    Multiple-unit activity of the prefrontal cortex and mediodorsal thalamic nucleus during reversal learning of discriminative avoidance behavior in rabbits

    Brain Res.

    (1983)
  • S.A Stwertka

    Anterior limbic unit activity during delayed response in cats

    Behav. Brain Res.

    (1987)
  • J Talairach et al.

    The cingulate gyrus and human behaviour

    Electroenceph. clin. Neurophysiol.

    (1973)
  • T Uwano et al.

    Neuronal responsiveness to various sensory stimuli, and associative learning in the rat amygdala

    Neuroscience

    (1995)
  • D Zeng et al.

    Morphological heterogeneity within the cingulate cortex in rat: a horseradish peroxidase transport study

    Brain Res.

    (1991)
  • L Angelini et al.

    Focal lesion of the right cingulum: a case report in a child

    J. Neurol. Neurosurg. Psychiat.

    (1981)
  • J.F Bates et al.

    Prefrontal connections of medial motor areas in the rhesus monkey

    J. comp. Neurol.

    (1993)
  • A Bechara et al.

    Failure to respond autonomically to anticipated future outcomes following damage to prefrontal cortex

    Cerebral Cortex

    (1996)
  • C.J Bench et al.

    The anatomy of melancholia-focal abnormalities of cerebral blood flow in major depression

    Psychol. Med.

    (1992)
  • F.M Benes et al.

    Increased GABAA receptor binding in superficial layers of cingulate cortex in schizophrenics

    J. Neurosci.

    (1992)
  • S.T Carmichael et al.

    Connectional networks within the orbital and medial prefrontal cortex of macaque monkeys

    J. comp. Neurol.

    (1996)
  • Davis M. (1992) The role of the amygdala in conditioned fear. In The Amygdala: Neurobiological Aspects of Emotion,...
  • J Decety et al.

    Mapping motor representations with positron emission tomography

    Nature

    (1994)
  • O Devinsky et al.

    Contributions of anterior cingulate cortex to behaviour

    Brain

    (1995)
  • Drevets W. (1995) PET and the functional anatomy of major depression. In Emotion, Memory and Behavior (eds Nakajima T....
  • W.C Drevets et al.

    Subgenual prefrontal cortex abnormalities in mood disorders

    Nature

    (1997)
  • R.P Dum et al.

    The origin of corticospinal projections from the premotor areas in the frontal lobe

    J. Neurosci.

    (1991)
  • Dum R. P. and Strick P. L. (1993) Cingulate motor areas. In Neurobiology of Cingulate Cortex and Limbic Thalamus: A...
  • S Eifuku et al.

    Neuronal activity in the primate hippocampal formation during a conditional association task based on the subject's location

    J. Neurosci.

    (1995)
  • Finch D. M. (1993) Hippocampal, subicular, and entorhinal afferents and synaptic integration in rodent cingulate...
  • Gabriel M. (1993) Discriminative avoidance learning: a model system. In Neurobiology of Cingulate Cortex and Limbic...
  • E.A Gaffan et al.

    Disconnection of the amygdala from visual association cortex impairs visual reward association learning in monkeys

    J. Neurosci.

    (1988)
  • D Gaffan et al.

    Amygdalar interaction with the mediodorsal nucleus of the thalamus and the ventromedial prefrontal cortex in stimulus–reward associative learning in the monkey

    J. Neurosci.

    (1990)
  • Gautier-Smith P. C. (1970) Parasagittal and Falx Meningiomas. Appleton-Century-Crofts, New...
  • Cited by (66)

    • Neuronal ensemble dynamics in associative learning

      2022, Current Opinion in Neurobiology
    • Functions and Circuits of REM Sleep

      2019, Handbook of Behavioral Neuroscience
    • The roles of the reward system in sleep and dreaming

      2012, Neuroscience and Biobehavioral Reviews
    View all citing articles on Scopus
    View full text