ELECTROCHEMICAL NEUROTRANSMISSION CELLS IN THE CNS: (Not listed: epithelial cells in blood vessels and surrounding ventricles, meninges, choroid plexi) NEURONS GLIA Type Name Type Name LARGE Pyramidal SUPPORT Oligodendrocytes (Form myelin sheath) Motoneurons Astrocytes (Communicate long distances) (Form astrocytic end-feet) SMALL Granular Interneurons IMMUNE Microglia (Communicate locally) SHAPE Pyramidal Stellate Basket Purkinje NEURONS: 1. Do not replicate after early development - sorta 2. Are specialized to receive, transform and transmit information GLIA: 1. "Support" the neurons 2. Can replicate throughout life THE NEURON: HAS 3 MAJOR COMPONENTS: (See diagram) 1. The cell body 2. The dendrites 3. The axon THE CELL BODY: 1. Also known as the SOMA or the PERIKARYA 2. Contains all the usual cell machinery 3. Also the AXON HILLOCK - source of ACTION POTENTIAL THE DENDRITES: Specialized for receipt, transformation of information 1. The dendritic arbor - thick branches, very much like a tree 2. Dendritic spines - buds on dendrite, site of most synapses 3. Thought that 80% of dendritic synapses are excitatory THE AXON: Transmits information 1. Extremely thin 2. Multiply branched 3. Synaptic boutons and synaptic swellings 4. The myelin sheath and the node of Ranvier THE SYNAPSE: The site of chemical neurotransmission A specialization involving both PRESYNAPTIC and POSTSYNAPTIC membranes THE SYNAPTIC CLEFT: Contains extracellular fluid, sometimes enzymes, separates pre-and post-synaptic membranes. Post-synaptic thickening Synapses can be on dendritic spines, dendritic trunks, cell bodies, and on axons DUAL FUNCTION OF THE NEURON: The neuron (typically) uses both electronic and chemical processes to transmit information: Information is RECEIVED chemically at the synapse, at RECEPTORS located on the postsynaptic membrane: 1. Receptors, specialized molecular complexes on the postsynaptic membrane, then change this chemical information into a local change in membrane potential. 2. EPSPs and IPSPs: Receptor stimulation causes local changes in membrane potential which are Excitatory Post-Synaptic Potentials or Inhibitory Post-Synaptic Potentials. a. EPSPs increase the probability that the cell will fire, IPSPs reduce that probability Information is then TRANSFORMED and TRANSMITTED electronically: 1. TRANSFORMATION occurs at the DENDRITES and the AXON HILLOCK a. Dendrites summate a wide variety of local membrane potentials b. These spread passively to the axon hillock c. Bottlenecks in passive electronic summation: 1. Thin membranes, including synaptic spines 2. Dendrites, cell body and IPSPs c. When resulting membrane potential at the axon hillock passes a voltage threshold, the neuron FIRES, causing an all-or-none electronic pulse to pass down the axon membrane 2. TRANSMISSION occurs as this electrical potential travels along the axon Finally, information is passed on to TARGET NEURONS chemically at the presynaptic membrane, as the pulse releases neurotransmitter into the synaptic cleft CHEMICAL NEUROTRANSMISSION: Occurs at the synapse as neurochemicals are released from the presynaptic membrane, diffuse across the synaptic cleft, and bind to postsynaptic receptors. TYPES OF CHEMICAL NEUROTRANSMISSION: 1. Temporal: fast vs slow a. Fast transmission: receptor stimulation opens ionic channels or pores in the cell wall, allowing ions to enter or leave, hence rapidly altering membrane potential b. Slow transmission: Receptor stimulation triggers a cascade of events inside the cell. 2. Anatomically addressed: a. MOST neurotransmitters are located in discrete neuronal clusters in the brain, and transmit to other, specific target neurons 3. Inhibitory, modulatory, excitatory: all three types of effect are known 4. Focal vs volume transmission: a. Focal: point-to point transmission across a classic synapse b. Volume transmission: like hormones, some neurotransmitters are released into the extracellular fluid, and can diffuse considerable distances to reach postsynaptic receptors NEUROTRANSMITTERS: There are hundreds of known neurotransmitters, but many can be classified into families: AMINES: A. Monoamines: i. Catecholamines: Dopamine, norepinephrine, epinephrine ii. Indolamines: Serotonin B. Acetylcholine AMINO ACIDS: i. Excitatory: Glutamate, aspartic acid ii. Inhibitory: GABA, glycine GASES: Nitric oxide, carbon monoxide PEPTIDES: All of the above are relatively SMALL molecules; peptides are complex proteins which are much larger. Some families include: Endogenous Opioids Hypothalamic hormone releasing factors Pituitary hormone releasing factors Circulating hormones Gut hormones etc: None of the above SYNTHESIS: 1. Most neurotransmitters are synthesized within the synaptic bouton 2. This synthesis involves: a. Enzymes produced in the cell body and transported down the axon i. Axonal transport: Fast, slow, anterograde, retrograde b. Substrate, transported from the cell body or taken up locally STORAGE: There are probably SEVERAL storage sites in the synaptic bouton: a. Vesicles: Small ping-pong balls made of cell membrane i. Uptake sites - get NTs into the vesicle ii. Production and destruction of vesicles NEUROTRANSMITTER RELEASE: 1. The nervous impulse opens Ca2+ channels in the cell wall of the synaptic bouton 2. Ca2+ influx causes the vesicles to attach to binding sites on the synaptic membrane and fuse to the membrane, releasing their contents into the synaptic cleft. DEACTIVATION: Necessary to turn the impulse OFF 1. Bound neurotransmitter dissociates from the postsynaptic receptor complex 2. At this point, one or both of 2 things happens: a. Enzymes in the synaptic cleft convert the NT into a non-binding form b. NT uptake sites on the presynaptic membrane bind to the NT and pull it back into the cell i. Once back inside the cell, other enzymes will often metabolize the NT CO-LOCALIZATION OF NEUROTRANSMITTERS: It is now thought that the nerve impulse releases several NTs simultaneously from a single bouton a. Often, these are packaged inside the same vesicle b. But bind to different receptors, with different effects