Amygdalo‐cortical sprouting continues into early adulthood: Implications for the development of normal and abnormal function during adolescence

Adolescence is a critical stage for the development of emotional maturity and diverse forms of psychopathology. The posterior basolateral nucleus of the amygdala is known to mediate fear and anxiety and is important in assigning emotional valence to cognitive processes. The medial prefrontal cortex, a homologue of the human anterior cingulate cortex, mediates emotional, attentional, and motivational behaviors at the cortical level. We postulate that the development of connectivity between these two corticolimbic regions contributes to an enhanced integration of emotion and cognition during the postnatal period. In order to characterize the development of this relay, injections of the anterograde tracer biocytin were stereotaxically placed within the posterior basolateral nucleus of the amygdala of rats at successive postnatal time points (postnatal days 6–120). Labeled fibers in the medial prefrontal cortex were evaluated using a combination of brightfield, confocal, and electron microscopy. We found that the density of labeled fibers originating from the posterior basolateral nucleus shows a sharp curvilinear increase within layers II and V of the anterior cingulate cortex and the infralimbic subdivisions of medial prefrontal cortex during the late postweanling period. This increase was paralleled by a linear rise in the number of axospinous and axodendritic synapses present in the neuropil. Based on these results, we propose that late maturation of amygdalo‐cortical connectivity may provide an anatomical basis for the development and integration of normal and possibly abnormal emotional behavior during adolescence and early adulthood. J. Comp. Neurol. 453:116–130, 2002. © 2002 Wiley‐Liss, Inc.

[1]  F. Benes,et al.  Increased interaction of dopamine‐immunoreactive varicosities with GABA neurons of rat medial prefrontal cortex occurs during the postweanling period , 1996, Synapse.

[2]  F. Benes,et al.  Myelination of cortical-hippocampal relays during late adolescence. , 1989, Schizophrenia bulletin.

[3]  Joseph E LeDoux Emotion: clues from the brain. , 1995, Annual review of psychology.

[4]  Michael Davis,et al.  The role of the amygdala in fear and anxiety. , 1992, Annual review of neuroscience.

[5]  L. Swanson The Rat Brain in Stereotaxic Coordinates, George Paxinos, Charles Watson (Eds.). Academic Press, San Diego, CA (1982), vii + 153, $35.00, ISBN: 0 125 47620 5 , 1984 .

[6]  C. Hall An Introduction to Theories of Personality , 1985 .

[7]  R. Verwer,et al.  Postnatal development of amygdaloid projections to the prefrontal cortex in the rat studied with retrograde and anterograde tracers , 1996, The Journal of comparative neurology.

[8]  R. Adamec Individual differences in temporal lobe sensory processing of threatening stimuli in the cat , 1991, Physiology & Behavior.

[9]  F. Benes,et al.  Myelination of a key relay zone in the hippocampal formation occurs in the human brain during childhood, adolescence, and adulthood. , 1994, Archives of general psychiatry.

[10]  Y. Kaminer Addictive disorders in adolescents. , 1999, The Psychiatric clinics of North America.

[11]  Miles G. Cunningham,et al.  A hypothermic miniaturized stereotaxic instrument for surgery in newborn rats , 1993, Journal of Neuroscience Methods.

[12]  B. R. Hergenhahn,et al.  An Introduction to Theories of Personality , 1984 .

[13]  D. Safer Self-Reported Suicide Attempts by Adolescents , 1997, Annals of clinical psychiatry : official journal of the American Academy of Clinical Psychiatrists.

[14]  P. Maclean,et al.  Brain evolution relating to family, play, and the separation call. , 1985, Archives of general psychiatry.

[15]  B. Vogt,et al.  Contributions of anterior cingulate cortex to behaviour. , 1995, Brain : a journal of neurology.

[16]  Joseph E LeDoux,et al.  Why We Think Plasticity Underlying Pavlovian Fear Conditioning Occurs in the Basolateral Amygdala , 1999, Neuron.

[17]  G. Schoenbaum,et al.  Changes in Functional Connectivity in Orbitofrontal Cortex and Basolateral Amygdala during Learning and Reversal Training , 2000, The Journal of Neuroscience.

[18]  E. Terasawa,et al.  Electrophysiological study of the limbic system in the rat at onset of puberty. , 1968, The American journal of physiology.

[19]  H. Klüver,et al.  PRELIMINARY ANALYSIS OF FUNCTIONS OF THE TEMPORAL LOBES IN MONKEYS , 1939 .

[20]  J Belcher,et al.  Nonparametric methods. , 2001, Nurse researcher.

[21]  B. Berger,et al.  Development of the dopaminergic innervation of the rat cerebral cortex. A light microscopic immunocytochemical study using anti-tyrosine hydroxylase antibodies. , 1982, Brain research.

[22]  F. Vives,et al.  Electrophysiological study of the response of medial prefrontal cortex neurons to stimulation of the basolateral nucleus of the amygdala in the rat , 1991, Brain Research.

[23]  P. Yakovlev,et al.  The myelogenetic cycles of regional maturation of the brain , 1967 .

[24]  D L Rosene,et al.  Cingulate cortex of the rhesus monkey: I. Cytoarchitecture and thalamic afferents , 1987, The Journal of comparative neurology.

[25]  H. Pratt,et al.  Adolescent violence: concepts for a new millennium. , 2000, Adolescent medicine.

[26]  A. Beitz,et al.  Co-localization of glutamate and tubulin in putative excitatory neurons of the hippocampus and amygdala: An immunohistochemical study using monoclonal antibodies , 1989, Neuroscience.

[27]  J. Kagan,et al.  Temperamental factors in human development. , 1991, The American psychologist.

[28]  C. Olson,et al.  Functional heterogeneity in cingulate cortex: the anterior executive and posterior evaluative regions. , 1992, Cerebral cortex.

[29]  Gregory P. Lee,et al.  Different Contributions of the Human Amygdala and Ventromedial Prefrontal Cortex to Decision-Making , 1999, The Journal of Neuroscience.

[30]  F. Gray,et al.  Bilateral infarction of the anterior cingulate gyri and of the fornices Report of a case , 1981, Journal of the Neurological Sciences.

[31]  H. Uylings,et al.  Neuronal development in human prefrontal cortex in prenatal and postnatal stages. , 1990, Progress in brain research.

[32]  P. Goldman-Rakic,et al.  Synaptic development of the cerebral cortex: implications for learning, memory, and mental illness. , 1994, Progress in brain research.

[33]  P. Huttenlocher Synapse elimination and plasticity in developing human cerebral cortex. , 1984, American journal of mental deficiency.

[34]  G. Awatramani,et al.  Adolescent development alters stressor-induced Fos immunoreactivity in rat brain , 1998, Neuroscience.

[35]  J. Aggleton The functional effects of amygdala lesions in humans: A comparison with findings from monkeys. , 1992 .

[36]  R. Adamec Normal and Abnormal Limbic System Mechanisms of Emotive Biasing , 1978 .

[37]  H. Uylings,et al.  Development of the dopaminergic innervation in the prefrontal cortex of the rat , 1988, The Journal of comparative neurology.

[38]  H. Kita,et al.  Amygdaloid projections to the frontal cortex and the striatum in the rat , 1990, The Journal of comparative neurology.

[39]  L. Spear The adolescent brain and age-related behavioral manifestations , 2000, Neuroscience & Biobehavioral Reviews.

[40]  A. D. Smith,et al.  Amygdala input to medial prefrontal cortex (mPFC) in the rat: A light and electron microscope study , 1996, Brain Research.

[41]  B. Vogt,et al.  Connections of the Monkey Cingulate Cortex , 1993 .

[42]  S. Kools Prevention of Mental Health Problems in Adolescence , 1998, Annual Review of Nursing Research.

[43]  J. Price,et al.  Projections from the amygdaloid complex to the cerebral cortex and thalamus in the rat and cat , 1977, The Journal of comparative neurology.

[44]  Joseph E. LeDoux,et al.  Emotional memory systems in the brain , 1993, Behavioural Brain Research.