Progressin Neurobiolooy, 1977,Vol.8, pp. 119 181.PergamonPress. Printedin Great Britain LOCALIZATION OF TRANSMITTER CANDIDATES IN THE BRAIN: THE HIPPOCAMPAL FORMATION AS A MODEL JON STORM-MATHISEN Norwegian Defence Research Establishment, Division for Toxicology, PO Box 25-N-2007 Kjeller, Norway Contents 1. Introduction 2. Identifying the transmitter of a neurone 2.1. Criteria 2.2. The transmitter candidates and their markers 2.2.1. ~,-Aminobutyric acid (GABA) 2.2.2. Acetylcholine 2,2.3. Aromatic amines 2.2.4. Acidic amino acids 2.3. Procedures for localizing transmitter candidates to specific neurones by neurochemical techniques 2,3.1. Topography 2,3.2. Fractionation of homogenates 2,3.3. Denervation studies 3. Survey of the anatomy and electrophysiology of the hippocampal formation 3.1. Gross anatomy 3.2. Histological organization and fibre connections 3.2.1. Layers 3.2.2. Axons of pyramidal and granular cells 3.2.3. Afferents, other than those from granular and pyramidal cells 3.2.4. Interneurones 3.2.5. Lamellar organization 3.2.6. Metal-containing pathways 3.3. Fine structure 3.3.1. Types of nerve endings 3.3.2. Quantitative composition of tissue 3.4. Electrophysiology, brief account 4. Localization of transmitter candidates in the hippocampal formation 4.1. ~-Aminobutyric acid 4.1.1. Topographical distribution 4.1.2. Subcellular distribution 4.1.3. Denervation studies 4.1.4. Physiological and pharmacological data 4.1.5. Comments 4.2. Acetylcholine 4.2.1. Topographical distribution 4.2.2. Subcellular distribution 4.2.3. Denervation studies 4.2.4. Physiological and pharmacological data 4.3. Aromatic amines 4.3.1. Noradrenaline 4.3.2. Dopamine 4.3.3. 5-hydroxytryptamine (serotonin) 4.3.4. Histamine 4.4. Acidic amino acids 5. Summary and conclusions List of abbreviations References 119 120 120 121 121 125 127 130 132 132 132 133 135 135 136 136 137 137 138 138 139 140 140 140 141 142 142 142 145 145 146 147 148 148 152 152 156 156 156 159 159 161 161 163 163 164 1. Introduction It is generally believed that neurones in the brain communicate with each other through the release of a transmitter substance from their nerve terminals, and further, that each type of neurone releases the same transmitter substance at all of its terminals. These principles were inferred more than 40 years ago (Dale, 1935) and have yet to be disproved. Although certain neurones in invertebrates apparently, can synthetize more 119