Comparative analyses of the neuron numbers and volumes of the amygdaloid complex in old and new world primates

The amygdaloid complex (AC), a key component of the limbic system, is a brain region critical for the detection and interpretation of emotionally salient information. Therefore, changes in its structure and function are likely to provide correlates of mood and emotion disorders, diseases that afflict a large portion of the human population. Previous gross comparisons of the AC in control and diseased individuals have, however, mainly failed to discover these expected correlations with diseases. We have characterized AC nuclei in different nonhuman primate species to establish a baseline for more refined comparisons between the normal and the diseased amygdala. AC nuclei volume and neuron number in 19 subdivisions are reported from 13 Old and New World primate brains, spanning five primate species, and compared with corresponding data from humans. Analysis of the four largest AC nuclei revealed that volume and neuron number of one component, the central nucleus, has a negative allometric relationship with total amygdala volume and neuron number, which is in contrast with the isometric relationship found in the other AC nuclei (for both neuron number and volume). Neuron density decreases across all four nuclei according to a single power law with an exponent of about minus one‐half. Because we have included quantitative comparisons with great apes and humans, our conclusions apply to human brains, and our scaling laws can potentially be used to study the anatomical correlates of the amygdala in disorders involving pathological emotion processing. J. Comp. Neurol. 518:1176–1198, 2010. © 2009 Wiley‐Liss, Inc.

[1]  D. Amaral,et al.  Organization of the intrinsic connections of the monkey amygdaloid complex: Projections originating in the lateral nucleus , 1998, The Journal of comparative neurology.

[2]  R. J. Smith.  Allometric scaling in comparative biology: problems of concept and method. , 1984, The American journal of physiology.

[3]  D. Bonthius,et al.  Use of frozen sections to determine neuronal number in the murine hippocampus and neocortex using the optical disector and optical fractionator. , 2004, Brain research. Brain research protocols.

[4]  J. C. Pruessner,et al.  Comprehensive dissection of the medial temporal lobe in AD: measurement of hippocampus, amygdala, entorhinal, perirhinal and parahippocampal cortices using MRI , 2006, Journal of Neurology.

[5]  R. Adolphs.  Recognizing emotion from facial expressions: psychological and neurological mechanisms. , 2002, Behavioral and cognitive neuroscience reviews.

[6]  David G. Amaral,et al.  Stereological Analysis of Amygdala Neuron Number in Autism , 2006, The Journal of Neuroscience.

[7]  K. Zilles,et al.  Evolution of the brainstem orofacial motor system in primates: a comparative study of trigeminal, facial, and hypoglossal nuclei. , 2005, Journal of human evolution.

[8]  R. Clark,et al.  Selective neurotoxic amygdala lesions in monkeys disrupt reactivity to food and object stimuli and have limited effects on memory. , 2003, Behavioral neuroscience.

[9]  D. Amaral,et al.  Role of the Primate Amygdala in Fear-Potentiated Startle: Effects of Chronic Lesions in the Rhesus Monkey , 2007, The Journal of Neuroscience.

[10]  R. Martin,et al.  Brain Size Allometry Ontogeny and Phylogeny , 1985 .

[11]  W. Hatton,et al.  Analysis of cell death in the trochlear nucleus of the chick embryo: Calibration of the optical disector counting method reveals systematic bias , 1999, The Journal of comparative neurology.

[12]  H. van Engeland,et al.  No evidence for preferential involvement of medial temporal lobe structures in high-functioning autism , 2006, Psychological Medicine.

[13]  J. Aggleton,et al.  Primate evolution and the amygdala , 2000 .

[14]  G. Pourtois,et al.  Distributed and interactive brain mechanisms during emotion face perception: Evidence from functional neuroimaging , 2007, Neuropsychologia.

[15]  J. Huxley,et al.  Terminology of Relative Growth , 1936, Nature.

[16]  J. Price,et al.  Low glial numbers in the amygdala in major depressive disorder , 2002, Biological Psychiatry.

[17]  Alan C. Evans,et al.  Volumetry of hippocampus and amygdala with high-resolution MRI and three-dimensional analysis software: minimizing the discrepancies between laboratories. , 2000, Cerebral cortex.

[18]  H. Stephan,et al.  Quantitative comparison of the amygdala in insectivores and primates. , 1977, Acta anatomica.

[19]  Khashayar Farsad,et al.  Comparative Vertebrate Neuroanatomy: Evolution and Adaptation , 1996, The Yale Journal of Biology and Medicine.

[20]  G. Striedter.  Principles of brain evolution. , 2005 .

[21]  D. Amaral,et al.  Stereological estimation of the number of neurons in the human amygdaloid complex , 2005, The Journal of comparative neurology.

[22]  Joseph E LeDoux.  Emotion circuits in the brain. , 2009, Annual review of neuroscience.

[23]  W. Strik,et al.  The amygdala in schizophrenia: a trimodal magnetic resonance imaging study , 2005, Neuroscience Letters.

[24]  H. Gundersen,et al.  Unbiased stereological estimation of the total number of neurons in the subdivisions of the rat hippocampus using the optical fractionator , 1991, The Anatomical record.

[25]  S. Shelton,et al.  The Role of the Central Nucleus of the Amygdala in Mediating Fear and Anxiety in the Primate , 2004, The Journal of Neuroscience.

[26]  B. Bogerts,et al.  Volume deficits of subcortical nuclei in mood disorders , 2005, European Archives of Psychiatry and Clinical Neuroscience.

[27]  D. Amaral,et al.  Distribution of reduced nicotinamide adenine dinucleotide phosphate diaphorase (NADPH‐d) cells and fibers in the monkey amygdaloid complex , 1991, The Journal of comparative neurology.

[28]  H. Frahm,et al.  Comparison of brain structure volumes in Insectivora and primates. VII. Amygdaloid components. , 1987, Journal fur Hirnforschung.

[29]  L. Goldstein.  The Amygdala: Neurobiological Aspects of Emotion, Memory, and Mental Dysfunction , 1992, The Yale Journal of Biology and Medicine.

[30]  B. Pakkenberg,et al.  Neocortical and hippocampal neuron and glial cell numbers in the rhesus monkey , 2007, Anatomical record.

[31]  B. Finlay,et al.  Linked regularities in the development and evolution of mammalian brains. , 1995, Science.

[32]  H. Gundersen,et al.  Unbiased stereological estimation of the number of neurons in the human hippocampus , 1990, The Journal of comparative neurology.

[33]  T. Crow,et al.  Amygdala volume in schizophrenia: post-mortem study and review of magnetic resonance imaging findings. , 2002, The British journal of psychiatry : the journal of mental science.

[34]  G. M. Halliday,et al.  Practical considerations for the use of the optical disector in estimating neuronal number , 1994, Journal of Neuroscience Methods.

[35]  D. Amaral,et al.  Amygdalectomy and responsiveness to novelty in rhesus monkeys (Macaca mulatta): generality and individual consistency of effects. , 2006, Emotion.

[36]  A. Schüz,et al.  Constancy and variability in cortical structure. A study on synapses and dendritic spines in hedgehog and monkey. , 1995, Journal fur Hirnforschung.

[37]  N J Emery,et al.  The effects of bilateral lesions of the amygdala on dyadic social interactions in rhesus monkeys (Macaca mulatta). , 2001, Behavioral neuroscience.

[38]  Yvette I. Sheline,et al.  Amygdala core nuclei volumes are decreased in recurrent major depression , 1998, Neuroreport.

[39]  J. Price.  Comparative Aspects of Amygdala Connectivity , 2003, Annals of the New York Academy of Sciences.

[40]  Charles F Stevens,et al.  Predicting Functional Properties of Visual Cortex from an Evolutionary Scaling Law , 2002, Neuron.

[41]  J. Haxby,et al.  Human neural systems for face recognition and social communication , 2002, Biological Psychiatry.

[42]  E. Crosby,et al.  Studies of the vertebrate telencephalon. III. The amygdaloid complex in the shrew (Blarina brevicauda) , 1944 .

[43]  Andrew Calder,et al.  Acquired theory of mind impairments in individuals with bilateral amygdala lesions , 2003, Neuropsychologia.

[44]  Nicole Barger,et al.  A comparative volumetric analysis of the amygdaloid complex and basolateral division in the human and ape brain. , 2007, American journal of physical anthropology.

[45]  Christopher S von Bartheld,et al.  Differential tissue shrinkage and compression in the z-axis: implications for optical disector counting in vibratome-, plastic- and cryosections , 2003, Journal of Neuroscience Methods.

[46]  Nicholas Lange,et al.  Neuron Numbers and Volume of the Amygdala in Subjects Diagnosed with Bipolar Disorder or Schizophrenia , 2007, Biological Psychiatry.

[47]  R. J. Smith,et al.  Body mass in comparative primatology. , 1997, Journal of human evolution.

[48]  Chet C. Sherwood,et al.  Evolution of Specialized Pyramidal Neurons in Primate Visual and Motor Cortex , 2003, Brain, Behavior and Evolution.

[49]  L. Bitensky.  Histochemistry in Pathology , 1985 .

[50]  Patrick R Hof,et al.  Volume, neuron density and total neuron number in five subcortical regions in schizophrenia. , 2007, Brain : a journal of neurology.

[51]  B. Cragg.  The density of synapses and neurones in the motor and visual areas of the cerebral cortex. , 1967, Journal of anatomy.

[52]  P Lavenex,et al.  The expression of social dominance following neonatal lesions of the amygdala or hippocampus in rhesus monkeys (Macaca mulatta). , 2006, Behavioral neuroscience.

[53]  D. Amaral,et al.  Cholinergic innervation of the monkey amygdala: An immunohistochemical analysis with antisera to choline acetyltransferase , 1989, The Journal of comparative neurology.

[54]  Edmund T. Rolls,et al.  Neurophysiology and functions of the primate amygdala. , 1992 .

[55]  Christopher H. van Dyck,et al.  Volumetry of amygdala and hippocampus and memory performance in Alzheimer's disease , 2006, Psychiatry Research: Neuroimaging.

[56]  H. Frahm,et al.  New and revised data on volumes of brain structures in insectivores and primates. , 1981, Folia primatologica; international journal of primatology.