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Here we provide a review of the animal and human literature concerning the role of the amygdala in fear conditioning, considering its potential influence over autonomic and hormonal changes, motor behavior and attentional processes. A stimulus that predicts an aversive outcome will change neural transmission in the amygdala to produce the somatic, autonomic and endocrine signs of fear, as well as increased attention to that stimulus. It is now clear that the amygdala is also involved in learning about positively valenced stimuli as well as spatial and motor learning and this review strives to integrate this additional information. A review of available studies examining the human amygdala covers both lesion and electrical stimulation studies as well as the most recent functional neuroimaging studies. Where appropriate, we attempt to integrate basic information on normal amygdala function with our current understanding of psychiatric disorders, including pathological anxiety.

The amygdala: vigilance and emotion

http://apps.usd.edu/coglab/schieber/pdf/mishkin_etal_1983.pdf

Object vision and spatial vision: two cortical pathways

Endogenous pain control systems: brainstem spinal pathways and endorphin circuitry.

http://www.back-in-business-physiotherapy.com/images/files/DescendingControl.pdf

Descending control of pain.

even less so. It was therefore impossible for the functionally minded neuro­ scientist to design and execute experiments taking this heterogeneity into consideration. Even pharmacological studies with these peptides were difficult to interpret in a physiological framework. In 1982, thanks mainly to the recombinant DNA techniques, we learned that all these peptides belong to three genetically distinct peptide families, as we describe below. We now know a great deal more about their anatomy, and we are beginning to clarify their biosynthetic pathways. Suddenly, we can think in terms of circuits rather than in "humors" or in black boxes. In our study offunction, we can no longer ignore the multiple systems, any more than the student of monoamines can ignore differences between dopaminergic and noradrenergic systems. Less clear, but equally critical, is the issue of multiple opioid receptors. Unquestionably, the heterogeneity exists. What remains to be established is whether each of the three families of opioids has its own receptor, or whether a given family can interact with more than one SUbtype, and each receptor subtype with more than one family. More critical to physiology is whether

Endogenous Opioids: Biology and Function

While there is an abundance of pharmacological and biochemical evidence to suggest the existence of multiple opioid receptors, their precise localization within the brain is unclear. To help clarify this issue, the present study examined the distributions of the mu, delta, and kappa opioid receptor subtypes in the rat forebrain and midbrain using in vitro autoradiography. Mu and delta receptors were labeled with the selective ligands 3H-DAGO (Tyr- D-Ala-Gly-MePhe-Gly-ol), and 3H-DPDPE (D-Pen2, D-Pen5-enkephalin), respectively, while the kappa receptors were labeled with 3H-(-)bremazocine in the presence of unlabeled DAGO and DPDPE. Based on previous findings in our laboratory, the labeling conditions were such that each ligand selectively occupied approximately 75% of each of the opioid sites. The results demonstrated that all 3 opioid receptor subtypes were differentially distributed in the rat brain. Mu binding was dense in anterior cingulate cortex, neocortex, amygdala, hippocampus, ventral dentate gyrus, presubiculum, nucleus accumbens, caudate putamen, thalamus, habenula, interpeduncular nucleus, pars compacta of the substantia nigra, superior and inferior colliculi, and raphe nuclei. In contrast, delta binding was restricted to only a few brain areas, including anterior cingulate cortex, neocortex, amygdala, olfactory tubercle, nucleus accumbens, and caudate putamen. Kappa binding, while not as widespread as observed with mu binding, was densely distributed in the amygdala, olfactory tubercle, nucleus accumbens, caudate putamen, medial preoptic area, hypothalamus, median eminence, periventricular thalamus, and interpeduncular nucleus. While all 3 opioid receptor subtypes could sometimes be localized within the same brain area, their precise distribution within the region often varied widely. For example, in the caudate putamen, mu binding had a patchy distribution, while delta and kappa sites were diffusely distributed, with delta sites being particularly dense ventrolaterally and kappa sites being concentrated ventromedially. These results support the existence of at least 3 distinct opioid receptors with possibly separate functional roles.

Autoradiographic differentiation of mu, delta, and kappa opioid receptors in the rat forebrain and midbrain

https://deepblue.lib.umich.edu/bitstream/handle/2027.42/25839/0000402.pdf;sequence=1

Anatomy of the CNS opioid systems

Dynorphin Immunocytochemistry in the Rat Central Nervous System

The immunocytochemical distribution of [Leu]enkephalin and an adrenal enkephalin precursor fragment (BAM-22P) immunoreactivity was investigated in the diencephalon and brainstem of rats pretreated with relatively high doses of colchicine (300-400 micrograms/10 microliters intracerebroventricularly). The higher ranges of colchicine pretreatment allowed the visualization of extensive enkephalin-containing systems in these brain regions, some of which are reported for the first time. Immunoreactive perikarya were found in many hypothalamic and thalamic nuclei, interpeduncular nucleus, substantia nigra, the colliculi, periaqueductal gray, parabrachial nuclei, trigeminal motor and spinal nuclei, nucleus raphe magnus and other raphe nuclei, nucleus reticularis paragigantocellularis, vestibular nuclei, several noradrenergic cell groups, nucleus tractus solitarius, as well as in the spinal cord dorsal horn. In addition to the above regions, immunoreactive fibers were also noted in the habenular nuclei, trigeminal sensory nuclei, locus coeruleus, motor facial nucleus, cochlear nuclei, dorsal motor nucleus of the vagus, and hypoglossal nucleus. When adjacent sections of those stained for [Leu]enkephalin were processed for BAM-22P immunoreactivity, it was found that these two immunoreactivities were distributed identically at almost all anatomical locations. BAM-22P immunoreactivity was generally less pronounced and ws preferentially localized to neuronal perikarya. The results of the present as well as the preceding studies (Khachaturian et al., '83) strongly suggest substantial structural similarity between the adrenal proenkephalin precursor and that which occurs in the brain. Also discussed are some differences and parallels between the distribution of [Leu]enkephalin and dynorphin immunoreactivities.

/pdf/enkephalin-systems-in-diencephalon-and-brainstem-of-the-rat-4xej795brd.pdf

Michael E. Lewis

Papers

Endogenous Opioids: Biology and Function

Autoradiographic differentiation of mu, delta, and kappa opioid receptors in the rat forebrain and midbrain

Anatomy of the CNS opioid systems

Dynorphin Immunocytochemistry in the Rat Central Nervous System

Enkephalin systems in diencephalon and brainstem of the rat