Marmara Medical Journal Volume 8 No:2 April 1995 EMPHASIS OF LIMBIC SYSTEM IN NEURAL CONCEPT OF EMOTION (Received 21 September, 1994) S. Baysal Akin, M.D.** / F. Onat, M.D.* ' Assistant Professor, Department o f Pharmacology, Faculty of Medicine, Marmara University, istanbul, Turkey. " Resident, Department of Pharmacology, Faculty o f Medicine, Marmara University, istanbul, Turkey. SUMMARY hypothalamus and its related structures and the cerebral cortex. In 1937, Papez described the limbic Anatomy and functions of limbic system and neural circuit, as well as Heinrich Klüver and Paul Bucy circuits within amygdala and hippocampus are dis­ reported their finding that bilateral destruction of the cussed in this review. As a conclusion it should be temporal lobe including several limbic structures such said that limbic system structures in the cortical regi­ as hippocampus and amygdala, produced dramatic ons are responsible for associative functions while changes in the emotional behaviour of monkeys. the subcortical part is included in the control of beha­ From these studies; Papez, Klüver and Bucy vioral patterns. submitted the background for many later theoretical and experimental approaches to the neurobiology of emotions. Modern anatomical studies have supported Key Words : Limbic cortex, amygdala, hippo­ Papez’s outline of the limbic system and added new campus, behaviour. connections (Fig. I). INTRODUCTION ANATOMY and FUNCTIONS OF LIMBIC SYSTEM The word limbic means "border" and the word limbic cortex was introduced firstly by Paul Broca. In the The limbic lobe Includes the parahippocampal gyrus, past, limbic system was used to describe the brain the cingulate gyrus and the subcallosal gyrus which Is structure that lies in the border region between the the anterior and inferior continuation of the cingulate Fig 1. A proposed neural circuit for emotion. The circuit originally proposed by Papez Is indicated by thick lines; more recently described connections are shown by fine lines. A pathway interconnecting the amygdala to limbic structures is shown. (From Kandal ER, Schwartz JH, Jessel TM; Principles of neural science, third edition) 100 Marmara Medical Journal Volume 8 No:2 April 1995 gyrus (1). It also includes the underlying cortex of the components of both autonomic and behavioral hippocampal formation. The hippocampal formation responses are represented at selected loci in the consists of the hippocampus proper, the dentate limbic system and hypothalamic regions. From these gyrus and the subiculum. Subiculum is the origin of maps, the dopamine is the transmitter in reward fibers in the fornix that innervate the hypothalamus. circuits. In a major review of the extensive research The amygdala is composed of many nuclei that are on reward, Wise and Rampre defined that dopamine reciprocally connected to the hypothalamus, plays an important role in the rewarding effects of hippocampal formation, neocortex and thalamus. It stimulating many brain regions but not of stimulating also receives an important afferent input from the either the frontal cortex or the nucleus accumbens olfactory system. (2). The latter effects depend on another transmitter (or transmitters); dopaminergic systems probably play The hypotalamus and limbic system mainly function a rather general role in motivation and movement. 10 together as a total system. It is also important that years later in the light of these studies, Stevens many of the behavioral functions elicited from the pioneered a new approach about the role of hypothalamus and other limbic system structures are dopamine in the neuroanatomy of schizophrenia (3). mediated through the reticular formation of the brain Postmortem studies documented increased stem. Hypothalamus is a coordinating center that dopamine concentration in the left amygdala in integrates various inputs to ensure appropriate set of patient with schizophrenia. Furthermore postmortem autonomic and somatic responses. Since these investigations of limbic cortical and subcortical responses are similar to those seen during some structures have abnormalities in the hippocampus, types of emotional behaviours, Hess suggested that amygdala and cingulate gyrus. MRI studies the hypothalamus integrates and coordinates the demonstrated structural abnormalities in the temporal behavioral expression of emotional states. In animals, lobe including a decreased volume of amygdala and some of the behavioral effects of stimulation of hippocampus (4,5). In parellel with these studies hypothalamus are the following: 1) Stimulation in the Weinberger concluded to describe the lateral hypothalamus causes thirst, eating, overt rage hyperdopaminergic limbic pathophysiology of and fighting; 2) Stimulation in ventromedial nuclei psychosis and the hypodopaminergic dorsolateral causes satiety and tranquility; 3) Stimulation of a thin prefrontal pathophysiology of negative symptoms of zone of periventricular nuclei results in fear and psychosis or schizophrenia. As an important punishment reactions. Lesion of these nuclei, in development in treatment of schizophrenia, clozapine general, causes the opposite effects. which is an antipsychotic and used in patients with persistent psychosis despite adequate classical The hypothalamus and limbic systems are intimately neuroleptic treatment has an interesting action. What concerned with emotional expression and with the interesting is its weak affinity for D2 dopamine genesis of emotions which have both mental and receptors and its limbic selectivity. physical components such as cognition, affect, conation and physical changes like sweating. There Role of Acetylcholine are particular neural circuits for numerous emotions localized in either localized brain lesions or electrical Another neurotransmitter functioning in limbic stimulation of specific areas. Neuro-pharmacological structure is acetylcholine. It has both excitatory and studies have tried to determine the role of specific inhibitory neuromodulator effects in the hippocampus. transmitters in particular emotions. Brain lesion Some cholinergic pathways are intrinsic to the studies involving experimentally-produced lesions in hippocampus but more than 90% of hippocampal animals have focused on some dramatic syndromes cholinergic fibers arise from mostly the medial of emotional change, such as the taming of monkeys septum and adjacent basal forebrain nuclei (6-9). following temporal lobe lesions. Brain stimulation Hippocampus is a useful model system that provides studies have generated brain maps for various selective investigation. Since there is recent evidence emotional responses, especially those involving that autoreceptor antagonists may have therapeutic aggression. utility for forebrain cholinergic neurodegeneration such as Alzheimer's disease (10, 11), it is thought that one of the mechanisms for regulation of NEURAL TRANSMISSION acetylcholine release involves inhibitory muscarinic autoreceptors (1 2). Role oi Dopamine On the other side, several studies have shown that Papez's proposed circuit has been the source of the nucleus basalis gives rise to a major cholinergic many experimental work. Each region in the circuit innervation of the neocortex, reticular thalamic and has been lesioned or electrically stimulated to basolateral amygdaloid nuclei (13, 14). It is determine the relation to emotional processing. Such hypothesized that in Alzheimer's disease and in aging stimulation may produce either rewarding or aversive process there is a deficit in functions of the effects or may elicid sequences of emotional muscarinic and nicotinic receptors and nucleus behaviour. More recently the maps of self stimulation basalis cholinergic projections (15, 16). Such studies sites have been done. This work has emphasized on have reported that lesioning of the nucleus basalis limbic system sites. Maps show that very discrete area by infusing ibotenic acid, an agonist of the 101 Marmara Medical Journal Volume 8 No:2 April 1995 N-methyl-D-aspartate subtype of glutamate persues the female. Amygdala could monitor all receptors, decreases cortical cholinergic activity modalities of sensory information. Olfactory impulse producing behavioral deficits to asses learning and from the main and accessory olfactory bulbs arrives memory functions (17-20). Another study related with within the corticomedial region while visual, auditory cholinergic effect on limbic structures was done by and somatosensory information is received by the Riekkinen et al. They examined on the hypothesis basolateral region. that passive avoidance performance is modulated via the amygdala by drugs acting on muscarinic and Due to the multiple connections, the amygdala has nicotinic cholinergic receptors (21). Results of these been called the "window” through which the limbic studies support the hypothesis and suggest that system sees the place of the person in the world. muscarinic and nicotinic receptor active drugs are Amygdala receives impulses from all portions of he effective on passive avoidance performance but limbic cortex, orbital surfaces of frontal lobe, the importance of the nucleus basalis to amygdala cingulate gyrus, the parahippocampal gyrus, cholinergic muscarinic and nicotinic system may be neocortex of the temporal, parietal and occipital lobes neglible in spatial learning (2 1 ). and auditory and visual associational areas. On the other hand it transmits signals back into these same The wellknown muscarinic cholinergic antogonist cortical areas, the hippocampus, the