The sections in this article are:


1
Essence of Prefrontal Function: Regulation of Behavior by Representational Knowledge
11
Subdivisions of Prefrontal Cortex

12
Global Nature of Prefrontal Syndrome in Humans

13
Animal Model for Prefrontal Function in Humans

14
Delayed-Response Tests and Varying Interpretations of Their Functional Significance

15
Distractability and Perseveration: Secondary Consequences of Basic Defect in Representational Memory

16
Representational Memory in Wisconsin Card Sort and Other Diagnostic Tests of Prefrontal Function in Humans

17
Localization of Delayed-Response Function: Principal Sulcus

18
Circuit Basis of Visuospatial Functions




2
Accessing and “On-Line” Processing of Representations in Visuospatial Domain: Parietal-Prefrontal Connections
21
Visuospatial Representational Memory in Humans

22
Spatial-Mnemonic Nature of Delayed-Response Deficit: Domain-Specific Memory Loss

23
Topography of Representational Memory in Prefrontal Cortex

24
Electrophysiological Evidence of Spatial-Mnemonic Processes in Principal Sulcus

25
Parietal-Prefrontal Connectivity

26
Columnar and Laminar Framework for Feedforward and Feedback Mechanisms

27
Functional Significance of Parietal-Prefrontal Collaboration




3
Long-Term Memory and “Off-Line” Processing: Prefrontal-Limbic Connections
31
Role of Hippocampus in Spatial Memory

32
Multiple Connections Between Principal Sulcus and Hippocampal Formation

33
Quadripartite Neural Network: Parietal-Temporal-Cingulate-Prefrontal Circuit

34
Limbic Contribution to Spatial Memory




4
Response Initiation and Inhibition: Projections to Striatum, Tectum, Thalamus, and Premotor Cortex
41
Motor-Control Functions of Prefrontal Cortex

42
Cortical-Striatal Pathway and Related Feedback Loops

43
Cortical-Tectal Pathway

44
Thalamic-Cortical Systems

45
Prefrontal-Premotor Connections: Anterior Supplementary Motor Cortex Relays

46
Functional Speculations




5
Modulatory Mechanisms: Brain Stem Catecholamine Projections
51
Activation of Cognitive Machinery

52
Concentration and Synthesis of Catecholamines in Primate Cortex

53
Brain Stem Innervation of Prefrontal Cortex

54
Delayed-Response Deficits and Recovery Produced by Catecholamine Loss and Replacement in Prefrontal Cortex

55
Circuit Basis for Neuromodulation in Principal Sulcus




6
Multiple Subsystems of Prefrontal Cortex: Unity or Diversity of Function
61
Unity or Diversity of Prefrontal Function

62
Frontal Eye Fields

63
Inferior Convexity

64
Orbital Prefrontal Cortices

65
Problem of Integration




7
Diseases Affecting Prefrontal Cortex
71
Schizophrenia: Loss of Corticocortical Processing and Regulation of Behavior by Representational Knowledge

72
Wernicke-Korsakoff Syndrome: Loss of Thalamocortical and Brain Stem Modulatory Mechanisms

73
Huntington's Chorea and Parkinson's Disease: Loss of Prefrontal-Striatal Mechanisms and Initiation or Inhibition of Motor Response

74
Overview of Neurobiology of Disease




8
Summary

Circuitry of Primate Prefrontal Cortex and Regulation of Behavior by Representational Memory

Distribution of α2 agonist binding sites in the rat and human central nervous system: Analysis of some functional, anatomic correlates of the pharmacologic effects of clonidine and related adrenergic agents

Presynaptic regulation of neurotransmitter release in the brain: facts and hypothesis

This study provides evidence that the alpha 2-adrenergic receptor agonist clonidine ameliorates the cognitive deficits exhibited by aged nonhuman primates through drug actions at alpha 2 receptors. Furthermore, pharmacological profiles in animals with lesions restricted to the dorsolateral prefrontal cortex indicate that this area may be the site of action for some of clonidine's beneficial effects. These results demonstrate that alpha-adrenergic systems contribute to cognitive function and suggest a new strategy for treating memory disorders in aged humans.

http://science.sciencemag.org/content/sci/230/4731/1273.full.pdf

Alpha 2-adrenergic mechanisms in prefrontal cortex associated with cognitive decline in aged nonhuman primates

Selective 35S-labeled oligonucleotide probes were designed to sequences of the rat alpha-2A (RG20), alpha-2B (RNG), and alpha-2C (RG10) adrenoreceptor mRNAs for use in in situ hybridization experiments on sections of unfixed rat brain, spinal cord and kidney. After hybridized sections were exposed to film or dipped in autoradiographic emulsion, specific and selective labeling patterns characteristic for each probe and region of the central nervous system were observed. Alpha-2A mRNA labeling was most pronounced in neurons in layer six of the cerebral cortex, hypothalamic paraventricular nucleus, reticular thalamic nucleus, pontine nuclei, locus coeruleus, vestibular nuclei, trapezoid nuclei, deep cerebellar nuclei, nucleus tractus solitarii, ventrolateral medullary reticular formation, and the intermediolateral cell column of the thoracic spinal cord. In some of these locations, the receptor mRNA, in all probability, is present in noradrenaline and perhaps adrenaline neurons. The alpha-2B probe, which primarily labels the kidney, gave only a very light signal in the thalamus in the central nervous system after extended exposure times. Alpha-2C mRNA labeling was primarily observed in the olfactory bulb, cerebral cortex, islands of Calleja, striatum, hippocampal formation, cerebellar cortex, and dorsal root ganglia. Labeling patterns disappeared when excess unlabeled probes were added to their respective radiolabeled probes, or when sense probes were employed. When a hybrid antisense probe homologous to all three alpha-2 probes was used, labeling patterns also disappeared. The present study therefore justifies the pharmacological subclassification of alpha-2 receptors by providing anatomical evidence for specific and selective cell groups in the rat central nervous system containing mRNA for three alpha-2 receptor subtypes. © 1993 Wiley-Liss, Inc.

Distributions of mRNAs for alpha-2 adrenergic receptor subtypes in rat brain: an in situ hybridization study.

[3H]Clonidine (26.7 Ci/mmole) binds with high affinity to sites on rat brain membranes with properties of alpha -noradrenergic receptors. [3H]Clonidine binding shows a biphasic pattern in kinetic and saturation experiments. Fifty percent of the specific binding of 0.4 nM [3H]clonidine is dissociated rapidly in 2 min by excess norepinephrine or clonidine, and the remaining 50% dissociates at a 10-fold slower rate. When slowly-dissociating [3H]clonidine binding is examined in isolation, saturation curves show a single population of high-affinity sites with a KD of 0.5 nM and B max of 1.3-1.6 pmoles/g tissue in cerebral cortex. Rapidly-dissociating [3H]clonidine binding, estimated from the difference between total binding and high-affinity binding, involves a single population of lower affinity sites with a KD of 3.0 nM and B max of 9-10 pmoles/g cerebral cortex tissue. Alpha agonists are in general more potent at the high affinity [3H]clonidine site, while alpha antagonists are more potent at the low affinity site. α-Methylnorepinephrine is less potent than norepinephrine at the high affinity site, but more potent at the low affinity site. Neither [3H]-clonidine binding site resembles the alpha receptor site labeled by [3H]WB-4101. The distribution of high and low affinity [3H]clonidine binding throughout rat central nervous system is different. High affinity binding levels vary 14 fold between lowest values in corpus striatum and cerebellum, and highest values in cerebral cortex. Low affinity binding varies less regionally, with highest levels in hypothalamus. 6-Hydroxydopamine treatment doubles the number of high affinity [3H]clonidine sites in the cortex, but does not alter the number of low affinity sites. 6-Hydroxydopamine increases high affinity binding much more than low affinity binding throughout the brain. 6-Hydroxydopamine also increases by 50% the number of [3H]WB-4101 and [3H]epinephrine alpha receptor sites in the cerebral cortex.

ACKNOWLEDGMENTS We thank Mrs. Lynda Hester for excellent technical assistance, and Pam Morgan and Billie Jean Little for manuscript preparation.

Bechtel Wd

Papers

Multiple apparent alpha-noradrenergic receptor binding sites in rat brain: effect of 6-hydroxydopamine.