Corticomedial Complex Research Articles

The amygdala of the common shrew, guinea pig, rabbit, fox and pig: five flavours of the mammalian amygdala as a consequence of clade-specific mosaic-like evolution.

The amygdala is a part of neural networks that contribute to the regulation of emotional behaviours and emotional learning, stress response, and olfactory, pheromonal and reproductive functions. All these various functions are processed by the three main functional systems, frontotemporal, autonomic and olfactory, which are derived from different telencephalic sources (claustrum, striatum and olfactory cortex) and are represented, respectively, by the basolateral complex (BLC), the central complex (CC) and corticomedial complex (CMC) of the amygdala. The question arises of how these three functional systems evolved during mammalian phylogeny to fit the amygdala to specific needs of various animals. In the present study, we provide quantitative information regarding the individual volumes and neuron numbers in the BLC, CC and CMC of the common shrew, guinea pig, rabbit, fox and pig, a series of animals arranged according to increasing size and complexity of the brain. The results show that, in this series of animals, the BLC underwent a gradual size increase in volume and number of neurons, whereas the CMC was gradually reduced with regard to both these measures. The CC was more or less conserved across studied species. For example, the volume of the amygdala in pigs is ~250 times larger than that in shrews and it also has almost 26 times as many neurons as the amygdala of shrews. However, the volumes of the BLC, CC and CMC were ~380, 208 and 148 times larger, respectively, in pigs than in shrews. The number of neurons in these three regions was ~38, 23 and 20 times greater, respectively, in pigs than in shrews. The results also show striking morphometric similarities of the amygdala in the guinea pig and rabbit as well as fox and pig. For example, the percentages of neurons in the fox and pig are 42.23% and 42.78%, respectively, for the BLC, 16.64% and 16.58%, respectively, for the CC, and 41.12% and 40.64%, respectively, for the CMC. In conclusion, our results indicate that the amygdala does not evolve as a single unit but, instead, the three main functional systems evolved independently, which suggests that brain structures with major functional links evolve together independently of evolutionary changes in other unrelated structures. The size progression of the BLC parallels the size progression of the neocortex with which it is strongly functionally linked, whereas the CMC is strongly connected to olfactory regions, and all these structures follow the same regression course. Remarkable morphometric similarity of the amygdala in the guinea pig and rabbit as well as in the fox and pig, however, suggest that there must also be another mechanism shaping the morphology of the amygdala and the brain during evolution. The gradual nature of size changes in the BLC and CMC support this hypothesis as well.

Impaired recognition of fear in voices and reduced anxiety after unilateral temporal lobe resection

It has been reported that bilateral amygdala damage in humans compromises the recognition of fear and anger in nonverbal vocalizations (Scott et al., 1997). We addressed the possibility that unilateral temporal lobe damage might be sufficient to impair fear recognition in voices. For this purpose, we tested patients after left (n=10) or right (n=8) medial temporal lobe resection for the relief of intractable epilepsy using a set of nonverbal vocalizations (Belin, Fillion-Bilodeau, & Gosselin, 2008). To focus more narrowly on the role of amygdala subparts, we differentiated patients with complete amygdala damage vs. damage limited to the basolateral complex of the amygdala. The results confirmed for the first time that unilateral amygdala lesion including the basolateral complex can selectively impair recognition of fear and surprise expressed by voices, supporting the notion that the amygdala is a multimodal structure. Interestingly, this impairment was observed in patients with incomplete resection of the amygdala that spared the central nucleus and the corticomedial complex, suggesting that a resection of the basolateral complex is sufficient to affect fear recognition. Given that fear has often been considered as a precursor of anxiety, we also investigated the effect of such lesions on self-reported anxiety. The same patients appeared to be less anxious than control participants in their mood questionnaires. The association of impaired fear perception and decreased anxiety level is considered in the light of recent human and animal data, providing support for a neurobiological basis of mood changes in patients with unilateral temporal lobe damage.

Aβ Accelerates the Spatiotemporal Progression of Tau Pathology and Augments Tau Amyloidosis in an Alzheimer Mouse Model

Senile plaques formed by β-amyloid peptides (Aβ) and neurofibrillary tangles (NFTs) formed by hyperphosphorylated tau, a microtubule-associated protein, are the hallmark lesions of Alzheimer's disease (AD) in addition to loss of neurons. While several transgenic (Tg) mouse models have recapitulated aspects of AD-like Aβ and tau pathologies, a spatiotemporal mapping paradigm for progressive NFT accumulation is urgently needed to stage disease progression in AD mouse models. Braak and co-workers developed an effective and widely used NFT staging paradigm for human AD brains. The creation of a Braak-like spatiotemporal staging scheme for tau pathology in mouse models would facilitate mechanistic studies of AD-like tau pathology. Such a scheme would also enhance the reproducibility of preclinical AD therapeutic studies. Thus, we developed a novel murine model of Aβ and tau pathologies and devised a spatiotemporal scheme to stage the emergence and accumulation of NFTs with advancing age. Notably, the development of NFTs followed a spatiotemporal Braak-like pattern similar to that observed in authentic AD. More significantly, the presence of Aβ accelerated NFT formation and enhanced tau amyloidosis; however, tau pathology did not have the same effect on Aβ pathology. This novel NFT staging scheme provides new insights into the mechanisms of tau pathobiology, and we speculate that this scheme will prove useful for other basic and translational studies of AD mouse models.

Clinical correlates of selective pathology in the amygdala of patients with Parkinson's disease.

The amygdala exhibits significant pathological changes in Parkinson's disease, including atrophy and Lewy body (LB) formation. Amygdala pathology has been suggested to contribute to some clinical features of Parkinson's disease, including deficits of olfaction and facial expression. The degree of neuronal loss in amygdala subnuclei and the relationship with LB formation in non-demented Parkinson's disease cases have not been examined previously. Using stereological methods, the volume of neurones and the number of neurones in amygdala subdivisions were estimated in 18 prospectively studied, non-demented patients with Parkinson's disease and 16 age- and sex-matched controls. Careful exclusion (all cortical disease) and inclusion (non-demented, levodopa-responsive, idiopathic Parkinson's disease or controls) criteria were applied. Seven Parkinson's disease cases experienced well-formed visual hallucinations many years after disease onset, while nine Parkinson's disease cases and three controls were treated for depression. Anatomically, the amygdala was subdivided into the lateral nucleus, the basal (basolateral and basomedial) nuclei and the corticomedial (central, medial and cortical nuclei) complex. LB and Lewy neurites were identified by immunohistochemistry for alpha-synuclein and ubiquitin and were assessed semiquantitatively. LB were found throughout the amygdala in Parkinson's disease, being present in approximately 4% of neurones. Total amygdala volume was reduced by 20% in Parkinson's disease (P = 0.02) and LB concentrated in the cortical and basolateral nuclei. Lewy neurites were present in most cases but did not correlate with any structural or functional variable. Amygdala volume loss was largely due to a 30% reduction in volume (P = 0.01) and the total estimated number of neurones (P = 0.007) in the corticomedial complex. The degree of neurone loss and the proportion of LB-containing neurones in the cortical nucleus within this complex were constant across Parkinson's disease cases and neither variable was related to disease duration (R(2 )< 0.03; P > 0.5). The cortical nucleus has major olfactory connections and its degeneration is likely to contribute to the early selective anosmia common in Parkinson's disease. There was a small reduction in neuronal density in the basolateral nucleus in all Parkinson's disease cases, but no consistent volume or cell loss within this region. However, the proportion of LB-containing neurones in the basolateral nucleus was nearly doubled in cases that exhibited visual hallucinations, suggesting that neuronal dysfunction in this nucleus contributes to this late clinical feature. Detailed quantitation of the other amygdala subdivisions failed to reveal any other substantial anomalies or any associations with depression. Thus, the impact of Parkinson's disease on the amygdala is highly selective and correlates with both early and late clinical features.

Zinc-containing afferent projections to the rat corticomedial amygdaloid complex: a retrograde tracing study.

The mammalian amygdaloid complex is densely innervated by zinc-containing neurons. The distribution of the terminals throughout the region has been described, but the origins of these zinc-containing fibers have not. The present work describes the origins of one major component of the zinc-containing innervation of the amygdaloid complex, namely, the component that innervates the corticomedial complex. Selective labeling of zinc-containing axons was accomplished by intracerebral microinfusion of selenium anions (SeO3(2-)), a procedure that produces a ZnSe precipitate in zinc-containing axonal boutons with subsequent retrograde transport to the neurons of origin. After infusions of SeO3(2-) into combinations of cortical, medial, or amygdalohippocampal regions, retrogradely labeled zinc-containing somata were found in all amygdaloid nuclei except for the medial and central nuclei, the bed nucleus of the accessory olfactory tract, the nucleus of the lateral olfactory tract, and the anterior amygdaloid area. Extrinsic zinc-containing projections to the same amygdaloid terminal fields were found to originate from the infralimbic, cingulate, piriform, perirhinal and entorhinal cortices, and from the prosubiculum and CA1. Commissural zinc-containing projections were found to originate from the posterolateral and posteromedial cortical nuclei and from the posterior part of the basomedial nucleus. Zinc-containing neurons have been implicated in the pathophysiology of epilepsy, in cell death after seizure or stroke, and in Alzheimer's disease, all clinical conditions that involve the amygdaloid complex. Identification of the zinc-containing pathways is a prerequisite to the elucidation of zinc's role in these disorders.

Thalamus-recorded somatosensory evoked potentials in man: An analysis of early components

Because previous studies have emphasized the importance of the amygdala in the therapeutic actions of benzodiazepines and described differences in benzodiazepine receptor distribution between human and rat, this study examined the distribution of multiple benzodiazepine receptors in normal human amygdala by light microscopic autoradiography. Benzodiazepine receptors were labeled with [3H]flunitrazepam at 5 representative rostro-caudal levels. Type 1 and Type 2 receptors were differentiated by the addition of 200 nM CL218,872 to serial sections and subsequent analysis based on the differential occupancy at Type 1 and Type 2 receptors by this drug. Results demonstrated that like the rat amygdala, human amygdala contains a higher density of benzodiazepine receptors in the basolateral nuclear complex compared to the corticomedial complex, and more Type 2 than Type 1 receptors overall. However, while rat amygdala is enriched rostrally in Type 1 receptors, this subclass in humans is elevated caudally. Pathways including the amygdala and limbic and cortical targets of its efferents may be preferential loci of benzodiazepine anxiolytic activity.

Multiple benzodiazepine receptors: autoradiographic localization in normal human amygdala

Because previous studies have emphasized the importance of the amygdala in the therapeutic actions of benzodiazepines and described differences in benzodiazepine receptor distribution between human and rat, this study examined the distribution of multiple benzodiazepine receptors in normal human amygdala by light microscopic autoradiography. Benzodiazepine receptors were labeled with [ 3H]flunitrazepam at 5 representative rostro-caudal levels. Type 1 and Type 2 receptors were differentiated by the addition of 200 nM CL218,872 to serial sections and subsequent analysis based on the differential occupancy at Type 1 and Type 2 receptors by this drug. Results demonstrated that like the rat amygdala, human amygdala contains a higher density of benzodiazepine receptors in the basolateral nuclear complex compared to the corticomedial complex, and more Type 2 than Type 1 receptors overall. However, while rat amygdala is enriched rostrally in Type 1 receptors, this subclass in humans is elevated caudally. Pathways including the amygdala and limbic and cortical targets of its efferents may be preferential loci of benzodiazepine anxiolytic activity.

Quantitative 3H-thymidine radiographic analyses of neurogenesis in the rat amygdala.

AbstractNeurogenesis in the rat amygdala was examined with 3H‐thymidine radiography. The animals were the offspring of pregnant females given two injections of 3H‐thymidine on consecutive days in an overlapping series: Embryonic day (E) 12 + E13, + E14. E21 + E22. On 60 days of age, the percentage of labelled cells and the proportion of cells added during each day of formation were determined at several anatomical levels within the following components of the amygdala: anterior amygdaloid area, bed nuclei of the lateral and accessory olfactory tracts, central, medial, anterior cortical, posterolateral cortical, posteromedial cortical, basomedial, basolateral, and lateral nuclei, the amygdalo‐hippocampal area, and the intercalated masses.All large and many small neurons originate in most nuclei between E13 and E17, those in the intercalated masses between E15 and E19, those in the amygdalo‐hippocampal area between E16 and E19. The anterior amygdaloid area, intercalated masses, central, medial, posterolateral cortical, posteromedial cortical, basomedial, basolateral, and lateral nuclei have strong rostral‐to‐caudal intranuclear gradients. There are five additional intranuclear gradients: 1) medial to lateral in the central nucleus, anterior amygdaloid area, and anterior intercalated masses; 2) lateral to medial in the bed nucleus of the lateral olfactory tract and basolateral nucleus; 3) superficial to deep in the amygdalo‐hippocampal area, posterolateral, and posteromedial cortical nuclei; 4) ventral to dorsal in the medial nucleus; and 5) dorsal to ventral between the small and large‐celled parts of the lateral nucleus. Only the bed nucleus of the accessory olfactory tract and the anterior cortical nucleus do not have intranuclear gradients. Between 10 and 15% of the total cell population in most nuclei are very small neurons and/or glia which originate simultaneously between E18 and E20. This population is absent in the ventral part of the medial, anterior cortical, and anterior basomedial nuclei; these contiguous areas may form a distinct subunit in the amygdala.In contrast to the pronounced intranuclear gradient, internuclear gradients are weak. Neurogenesis in the central nucleus and corticomedial and basolateral complexes appears to take place both concurrently and independently. There are groups of early‐originating neurons in the central, medial, and basolateral nuclei located near the periphery of the amygdala. Each of these groups is surrounded by younger neurons farther within the interior. The youngest calls are in the centrally placed intercalated masses. These settling patterns suggest that cells in the amygdala arise simultaneously from more than one neuroepithelial source during morphogenesis.The chronology of neurogenesis in the amygdala can be related to some of its anatomical connections. Rostral‐to‐caudal gradients in the corticomedial complex may be timed to coincide with early vs. late arrival of olfactory fibers. The subdivisions bases on intranuclear gradients in the central, medial, and basolateral nuclei match the subdivisions based on patterns of anatomical connections.

Olfactory relationships of the telencephalon and diencephalon in the rabbit. III. The ipsilateral centrifugal fibers to the olfactory bulbar and retrobulbar formations.

The axoplasmic retrograde transport of horseradish peroxidase (HRP) from axon terminals to their parent cell bodies and histochemical fluorescence microscopy have been used to study the ipsilateral centrifugal fibers to the olfactory bulbs and anterior olfactory nucleus in the rabbit. Focal injections of peroxidase were placed unilaterally into the main or accessory olfactory bulb or into the anterior olfactory nucleus. In animals with injected HRP confined within the main bulb, perikarya retrogradely labeled with the protein in the ipsilateral forebrain were observed in the anterior prepyriform cortex horizontal limb of the nucleus of the diagonal band, and far lateral preoptic and rostral lateral hypothalamic areas. Brain stem cell groups that contained HRP-positive somata include the locus coeruleus and midbrain dorsal raphe nucleus. Except for the prepyriform cortex, the basal forebrain structures with labeled perikarya correlate well with locations of cell bodies containing acetylcholinesterase and choline acetyltransferase. These somata may represent a cholinergic afferent system to the main olfactory bulb. Peroxidase-labeled cell bodies in the locus coeruleus and midbrain raphe are indicative of noradrenergic and serotonergic innervations respectively of the olfactory bulb. In rabbits in which peroxidase was injected or diffused into the accessory olfactory bulb and anterior alfactory nucleus, HRP-positive somata were identified in the prepyriform cortex bilaterally, the horizontal limb of the diagonal band nucleus, lateral hypothalamic region, nucleus of the lateral olfactory tract, corticomedial complex of the amygdala, mitral and tufted cell layers of the ipsilateral main olfactory bulb, locus coeruleus, and the midbrain raphe. Evidence for centrifugal fibers to the accessory olfactory bulb from the corticomedial complex of the amygdala, locus coeruleus, and possibly the nucleus of the lateral olfactory tract and midbrain raphe is discussed. A similar distribution of labeled perikarya in the forebrain and brain stem was seen in rats in which peroxidase injected into the main olfactory bulb had spread into the accessory bulb and anterior olfactory nucleus. Histochemical fluorescence microscopy of the main and accessory olfactory bulbs in the rabbit and rat revealed fine caliber, green fluorescent fibers and varicosities predominantly in the granule cell layer and less so among cells in the glomerular layer. In sections through the root of the main olfactory bulb, a similar fluorescence was seen in the deep half of the plexiform layer of the pars externa of the anterior alfactory nucleus. These fluorescent fibers likely represent the noradrenergic innervation of the olfactory bulbar and retrobulbar formations. A fluorescent yellow hue was observed in the glomerular layer of the main bulb and may signify a serotonergic innervation of this lamina...

Simultaneous stimulation of limbic system structures

The effect of single and simultaneous stimulation of pairs of limbic nuclei was assessed in chronic cats. Sites of stimulation were the nuclear subdivisions of the amygdala, septum and hippocampus. Behavioural, motor and electrocardiographic responses were observed. There was a separation of the zones where single stimulation results in bradycardia and tachycardia. Bradycardia could be elicited from the area amygdaloidea anterior, the anterior part of the nuclei amygdalae centralis and medialis, the nucleus amygdalae lateralis and the small-celled portion of the nucleus amygdalae basalis. Tachycardia was elicited from the septum, the posterior part of the nuclei amygdalae centralis and medialis and also from the large-celled portion of the nucleus amygdalae basalis. In the amygdala, the points inducing flight responses showed a bradycardia; and tachycardia followed electrical stimulation of the points yielding defence reactions, Simultaneous stimulation of the septum with the corticomedial complex or the area amygdaloidea anterior provoked an inhibition of motor or behavioural responses induced by individual stimulation of the corticomedial complex and the area amygdaloidea anterior. Inhibition of the electrocardiographic modifications induced by stimulation of the area amygdaloideanterior and the anterior part of the nucleus medialis was also observed upon concurrent stimulation of the septum. Stimulation of the posterior part of the nucleus centralis resulted in inhibition of the E.C.G. modifications elicited by the area amygdaloidea anterior and nucleus lateralis. Facilitation of E.C.G. responses in the nucleus lateralis and the small-celled portion of the basalis was observed by stimulation of the posterior and anterior parts of the nucleus medialis respectively.

Role of amygdaloid complex in sodium chloride and water intake in the rat

Abstract Bilateral electrolytic lesions in the amygdaloid complex of the rat elicited either a decrease or increase in 1.5 per cent NaCl intake. The studies were made employing the standard “two bottle” self-selection procedure. Lesions placed in the corticomedial complex, especially the cortical nucleus, resulted in an increase of NaCl and also of the total fluid intake. Bilateral lesions placed principally in the lateral nucleus but also reaching the medial, basolateral and basomedial nuclei resulted in a decrease of NaCl and total fluid ingestion. Sodium balance studies showed that changes in Na consumption preceded changes in urinary output. These results together with those already reported from our laboratory support the assumption of the existence of an intricate circuit related to hydromineral metabolism which involves the septal area, amygdala and hypothalamus.

The development of the human amygdala during early embryonic life.

AbstractThe development of the human amygdaloid complex is described beginning at the time that it first appears, when the cerebral hemispheres begin to evaginate (approximately 8‐‐9 mm), and including a fetus of 27.4 mm CR length Both Nissl and protargol silver series, transversely and sagittally sectioned, were used.The earliest cell migration representing the striatal complex is from the germinal epithelium in the region of the interventricular foramen, lateral to the primordial hippocampal formation. This is the characteristic topographic location of the amygdala, which, therefore, is the first portion of the human striatal complex to appear embryologically. All of the amygdaloid nuclei identified develop by the migration of neuroblasts from the germinal epithelium.The three main subdivisions of the amygdaloid complex (anterior amygdaloid area, corticomedial complex and basolateral nuclear group) are identifiable almost immediately after the primordial amygdala appears (9.5 mm in the material studied). In this embryo the cortical and medial nuclei are identifiable, but the central nucleus was not seen until 22.2 mm and the nucleus of the lateral olfactory tract was not identified even in the oldest fetuses.The basolateral complex differentiates much later than the corticomedial complex and all of the nuclear components became identifiable at the same time (20.7 mm embryo). However the basal nucleus is best represented, the accessory basal next in size, and the lateral only just appearing. In the oldest fetus the subdivisions of the basal and accessory basal nuclei seen in the adult brain are recognizable. Even before the individual nuclei appear, the basolateral complex is much larger than the corticomedial complex. The lateral to medial rotation of the amygdaloid complex has not yet begun in the oldest fetuses, but the posterior end of the lateral ventricle is beginning to turn anteriorly.During early development, all cells of the amygdala are derived from the lateral striatal ridge, the only one present until 14.0 mm. At 20.7 mm and later neuroblasts are contributed from the medial striatal ridge also. Although the greater part of the basolateral amygdaloid complex is derived from the lateral ridge, some cells are contributed from the medial ridge, particularly to the accessory basal nucleus. By contrast, the corticomedial complex is derived in part from the medial striatal ridge, after it appears, even though the early development is from the lateral ridge.Comparisons between the amygdala at different developmental stages and the amygdala in fishes, in amphibians, in reptiles and in lower mammals are made. The amygdala in fishes, in amphibians, in reptiles and in lower mammals are made. The topographic relationships between the amygdala and the hippocampal formation, the piriform cortex and the caudate, the putamen and the globus pallidus are considered.