The adrenal hormone corticosterone transcriptionally regulates responsive genes in the rodent hippocampus through nuclear mineralocorticoid and glucocorticoid receptors. Via this genomic pathway the hormone alters properties of hippocampal cells slowly and for a prolonged period. Here we report that corticosterone also rapidly and reversibly changes hippocampal signaling. Stress levels of the hormone enhance the frequency of miniature excitatory postsynaptic potentials in CA1 pyramidal neurons and reduce paired-pulse facilitation, pointing to a hormone-dependent enhancement of glutamate-release probability. The rapid effect by corticosterone is accomplished through a nongenomic pathway involving membrane-located receptors. Unexpectedly, the rapid effect critically depends on the classical mineralocorticoid receptor, as evidenced by the effectiveness of agonists, antagonists, and brain-specific inactivation of the mineralocorticoid but not the glucocorticoid receptor gene. Rapid actions by corticosterone would allow the brain to change its function within minutes after stress-induced elevations of corticosteroid levels, in addition to responding later through gene-mediated signaling pathways.

https://www.pnas.org/content/pnas/102/52/19204.full.pdf

Mineralocorticoid receptors are indispensable for nongenomic modulation of hippocampal glutamate transmission by corticosterone

Section I-Peripheral Nerve.- 1 Peripheral Nerve Structure.- 1. Introduction.- 2. Histology and Development.- 3. The Axon.- 3.1. Filaments and Microtubules.- 3.2. Other Organelles and the Axolemma.- 4. Sheaths of Axons.- 4.1. Schwann Cells.- 4.2. Myelin.- 4.3. Function of Schwann Cells and Their Myelin Sheaths.- 4.4. Connective Tissue Sheaths.- 5. References.- 2 The Nerve Impulse.- 1. Introduction.- 2. Passive Electrical Properties.- 3. Voltage-Clamp Analysis of the Ionic Current.- 4. Momentary Current-Voltage Relations.- 5. The Threshold Conditions for Excitation.- 6. Factors Determining Conduction Velocity.- 7. References.- 3 Axoplasmic Transport-Energy Metabolism and Mechanism.- 1. Introduction.- 2. Fast Axoplasmic Transport.- 2.1. Characterization.- 2.2. Mechanism and Energy Supply.- 2.3. Transport and Membrane Function.- 3. Slow Axoplasmic Transport.- 3.1. Characterization.- 3.2. Mechanism.- 4. References.- Section IIA-Junctional Transmission-Structure.- 4 Neuromuscular Junctions and Electric Organs.- 1. Introduction.- 2. The Typical Neuromuscular Junction.- 2.1. Distribution and Location of Nerve Terminals.- 2.2. The Axon.- 2.3. The Synaptic Space.- 2.4. Postjunctional Muscle Fiber.- 3. Variations of Motor End Plates.- 3.1. Variations from Class to Class.- 3.2. Endings on Slow-Twitch and Rapid-Twitch Fibers.- 3.3. Endings on Slow Tonic Muscle Fibers.- 4. Electric Organs.- 4.1. Electrocytes.- 4.2. Innervation and Ultrastructure.- 5. References.- 5 The Peripheral Autonomic System.- 1. Anatomical Considerations: Sympathetic and Parasympathetic Divisions.- 2. Morphological Observations.- 2.1. Preganglionic Neurons.- 2.2. Postganglionic Neurons.- 2.3. Adrenal and Extra-Adrenal Chromaffin Cells.- 3. References.- 6 Ultrastructure of Ganglionic Junctions.- 1. General Considerations.- 2. Sympathetic Ganglia.- 2.1. Amphibia.- 2.2. Reptiles.- 2.3. Mammals.- 2.4. Some Effects of Different Fixatives.- 3. Parasympathetic Ganglia.- 3.1. Ciliary Ganglion.- 3.2. Otic Ganglion.- 3.3. Ganglia of the Enteric Plexuses.- 3.4. Cardiac Ganglion Cells.- 4. Summary and Comment.- 5. References.- Section IIB-Junctional Transmission-Function.- 7(i) Neuromuscular Transmission-Presynaptic Factors.- 1. Synthesis, Storage, and Release of Acetylcholine.- 1.1. Synthesis of ACh.- 1.2. Storage and Release.- 2. The Acceleration of Release by Nerve Impulses.- 2.1. The Role of the Nerve Impulse.- 2.2. The Role of Ca2+.- 2.3. After- Effects of Depolarization-Secretion Coupling.- 3. References.- 7 (ii) Neuromuscular Transmission-The Transmitter-Receptor Combination.- 1. Introduction.- 2. Molecular Basis of Chemoelectric Transduction.- 3. Pharmacology.- 4. Chemical Nature of the Acetylcholine Receptor.- 5. Desensitization.- 6. References.- 7 (iii) Neuromuscular Transmission-Enzymatic Destruction of Acetylcholine.- 1. Location and Measurement of Cholinesterases at the Junction.- 1.1. Histochemical Staining.- 1.2. Microchemical Methods.- 1.3. Assay of External AChE.- 1.4. Radioautographic Methods.- 2. Amounts and Types of Cholinesterase at the Junctions.- 3. Requirement for AChE in Impulse Transmission.- 4. Relation of AChE to ACh- Receptors.- 5. Quantitative Relation of AChE to ACh at the End Plate.- 6. References.- 8 Ganglionic Transmission.- 1. Introduction.- 2. Response of Autonomic Ganglia to Preganglionic Volleys.- 2.1. Response of Normal Ganglia.- 2.2. Response of Curarized Ganglia.- 2.3. Slow Ganglionic Responses and Afterdischarges.- 3. Electrical Constants of Ganglion Cell Membrane.- 4. Action Potentials of Single Ganglion Cells.- 4.1. Response to Antidromic Stimulation.- 4.2. Response to Direct Intracellular Stimulation.- 4.3. Response to Orthodromic Stimulation.- 4.4. Ionic Requirement for Generation of Action Potential.- 5. Nature and Electrogenesis of Postsynaptic Potentials.- 5.1. The "Fast" Excitatory Postsynaptic Potential.- 5.2. The "Slow" Excitatory Postsynaptic Potential.- 5.3. The "Late Slow" Excitatory Postsynaptic Potential.- 5.4. The "Slow" Inhibitory Postsynaptic Potential.- 6. Cholinergic and Adrenergic Receptors at Preganglionic Nerve Terminals.- 6.1. Cholinergic Receptor Site.- 6.2. Adrenergic Receptor Site.- 7. References.- 9 Function of Autonomic Ganglia.- 1. Introduction.- 2. Ganglia as Coordinating Centers.- 2.1. The Relay Hypothesis of Ganglionic Function.- 2.2. Development of a Stochastic Hypothesis.- 3. Experimental Evidence.- 3.1. Observed Patterns of Innervation.- 3.2. Ganglionic Activity and Factors Influencing It.- 3.3. Relative Autonomy of Ganglia.- 4. Conclusions.- 5. References.- 10 Peripheral Autonomic Transmission.- 1. Introduction.- 2. Definition of the Autonomic Neuromuscular Junction.- 2.1. Relation of Nerve Fibers to Muscle Effector Bundles.- 2.2. Relation of Nerve Fibers to Individual Smooth Muscle Cells.- 3. Adrenergic Transmission.- 3.1. Introduction.- 3.2. Structure of Adrenergic Neurons and Storage of Noradrenaline.- 3.3. Electrophysiology of Adrenergic Transmission.- 3.4. Ionic Basis of the Action of Catecholamines on the Postjunctional Membrane.- 3.5. Summary.- 4. Cholinergic Transmission.- 4.1. Introduction.- 4.2. Localization of Acetylcholinesterase.- 4.3. Electrophysiology of Cholinergic Transmission.- 4.4. Ionic Basis of the Action of ACh on the Postjunctional Membrane.- 4.5. Summary.- 5. Purinergic Transmission.- 5.1. Introduction.- 5.2. Electrophysiology of Purinergic Transmission.- 5.3. Summary.- 6. Conclusions.- 7. References.- 11 "Trophic" Functions.- 1. Introduction.- 2. Regulation of Taste Buds.- 3. Regulation of Amphibian Limb Regeneration.- 4. Regulation of Physiological and Metabolic Properties of Muscle.- 4.1. Resting Membrane Potential.- 4.2. Acetylcholine Sensitivity.- 4.3. Cholinesterase Activity.- 4.4. The Role of ACh Release.- 4.5. The Dynamic Nature of the Muscle Fiber.- 4.6. Plasticity of the Motor Unit.- 5. Mechanisms of Neural Regulation.- 6. References.- Section III-Receptors-Structure and Function.- 12 Cutaneous Receptors.- 1. Introduction.- 2. Morphology of Cutaneous Nerves.- 2.1. Uniformity of Cutaneous Axons.- 2.2. Relative Numbers of Myelinated and Nonmyelinated Axons.- 3. Morphology of Cutaneous Receptors.- 3.1. Encapsulated Receptors.- 3.2. Unencapsulated Corpuscular Receptors.- 3.3. Noncorpuscular Receptors.- 4. Physiology of Cutaneous Receptors.- 4.1. Cutaneous Mechanoreceptors.- 4.2. Cutaneous Thermoreceptors.- 4.3. Nociceptors.- 5. References.- 13 The Pacinian Corpuscle.- 1. Introduction.- 2. Morphology.- 3. Afferent Responses to Mechanical Stimuli.- 4. Mechanical Properties of the Corpuscle.- 5. Receptor Potentials.- 6. Impulse Activity in the Nerve Terminal.- 7. Distribution of Pacinian Corpuscles.- 8. Central Effects of Impulses from Pacinian Corpuscles.- 9. References.- 14 Receptors in Muscles and Joints.- 1. Introduction.- 2. Joint Receptors.- 3. Tendon Organs.- 4. Muscle Spindles.- 4.1. Reptiles.- 4.2. Amphibia.- 4.3. Birds.- 4.4. Mammals.- 5. Uncertain Origin of Adaptation.- 6. References.- 15 Enteroceptors.- 1. Introduction.- 2. Methods.- 2.1. Histology.- 2.2. Physiology.- 3. Cardiovascular Receptors.- 3.1. Systemic Arterial Baroreceptors.- 3.2. Pulmonary Arterial Baroreceptors.- 3.3. Ventricular Receptors.- 3.4. Atriovenous Receptors.- 4. Respiratory System Receptors.- 4.1. Cough and Irritant Receptors.- 4.2. Pulmonary Stretch Receptors.- 4.3. Type J Receptors.- 4.4. Other Receptors.- 5. Alimentary System Receptors.- 5.1. Muscular Receptors.- 5.2. Serosal Receptors.- 5.3. Muscularis Mucosae Receptors.- 5.4. Chemoreceptors.- 5.5 Hepatic Osmoreceptors.- 6. Urinary Tract Receptors.- 6.1. Bladder.- 6.2. Urethra.- 7. Other Enteroreceptors.- 8. References.- 16 Arterial Chemoreceptors.- 1. Introduction.- 2. Structure.- 2.1. Light Microscopy.- 2.2. Electron Microscopy.- 2.3. Degeneration Studies.- 3. Function.- 3.1. Types of Activity in the Nerve Supply to the Receptor Complex.- 3.2. The Type I Cell.- 4. The Identity of the Receptor.- 4.1. The Received View.- 4.2. A New Hypothesis.- 5. References.- 17 Taste Receptors.- 1. Introduction.- 2. Gustatory Nerve Fiber Response to Chemical Stimuli.- 2.1. Multiple Sensitivity of Single Chorda Tympani Fibers.- 2.2. Neural Code for Quality of Taste and "Across-Fiber Pattern" Theory.- 3. Electrical Responses of Gustatory Cells to Chemical Stimuli.- 3.1. Innervation and Structure of Taste Bud.- 3.2. How Do Gustatory Cells Respond to Chemical Stimuli?.- 4. References.

The Peripheral Nervous System

The endogenous cannabinoid system has been shown to play a crucial role in controlling neuronal excitability and synaptic transmission. In this study we investigated the effects of a cannabinoid receptor (CB-R) agonist WIN 55,212-2 (WIN) on excitatory synaptic transmission in the rat ventral tegmental area (VTA). Whole-cell patch clamp recordings were performed from VTA dopamine (DA) neurons in an in vitro slice preparation. WIN reduced both NMDA and AMPA EPSCs, as well as miniature EPSCs (mEPSCs), and increased the paired-pulse ratio, indicating a presynaptic locus of its action. We also found that WIN-induced effects were dose-dependent and mimicked by the CB1-R agonist HU210. Furthermore, two CB1-R antagonists, AM281 and SR141716A, blocked WIN-induced effects, suggesting that WIN modulates excitatory synaptic transmission via activation of CB1-Rs. Our additional finding that both AM281 and SR141716A per se increased NMDA EPSCs suggests that endogenous cannabinoids, released from depolarized postsynaptic neurons, might act retrogradely on presynaptic CB1-Rs to suppress glutamate release. Hence, we report that a type of synaptic modulation, previously termed depolarization-induced suppression of excitation (DSE), is present also in the VTA as a calcium-dependent phenomenon, blocked by both AM281 and SR141716A, and occluded by WIN. Importantly, DSE was partially blocked by the D2DA antagonist eticlopride and enhanced by the D2DA agonist quinpirole without changing the presynaptic cannabinoid sensitivity. These results indicate that the two pathways work in a cooperative manner to release endocannabinoids in the VTA, where they play a role as retrograde messengers for DSE via CB1-Rs.

https://www.jneurosci.org/content/jneuro/24/1/53.full.pdf

Endocannabinoids Mediate Presynaptic Inhibition of Glutamatergic Transmission in Rat Ventral Tegmental Area Dopamine Neurons through Activation of CB1 Receptors

A genome-wide analysis of the human kinome — the sum total of protein, lipid and carbohydrate kinases — shows that the cell's signalling functions are intimately linked to endocytosis, the process by which material is imported into the cell inside a membrane vesicle. Many of the kinases involved in endocytosis are known to function in mitogenic signalling, stimulating cell division and lymphocyte transformation: this adds to growing evidence that endocytic transport and signal transduction are integrated processes. An accompanying manuscript looks at the role of some of the kinases identified in the kinome screen, revealing novel dynamic properties of caveola/raft-mediated endocytosis that are distinct from the current picture of membrane transport. A functional genomics approach has revealed that caveolae/raft-mediated endocytosis is subject to regulation by a large number of kinases1. Here we explore the role of some of these kinases in caveolae dynamics. We discover that caveolae operate using principles different from classical membrane trafficking. First, each caveolar coat contains a set number (one ‘quantum’) of caveolin-1 molecules. Second, caveolae are either stored as in stationary multi-caveolar structures at the plasma membrane, or undergo continuous cycles of fission and fusion with the plasma membrane in a small volume beneath the surface, without disassembling the caveolar coat. Third, a switch mechanism shifts caveolae from this localized cycle to long-range cytoplasmic transport. We have identified six kinases that regulate different steps of the caveolar cycle. Our observations reveal new principles in caveolae trafficking and suggest that the dynamic properties of caveolae and their transport competence are regulated by different kinases operating at several levels.

B. Katz

Papers

Quantal Mechanism of Neural Transmitter Release