Outline Neuroanatomy • Neuroanatomy Overview of the basics needed for this course • To know about drug action, have to know what a neuron is, where it is, and how neurons interact with each other • Digital Anatomist Program (will place link on website) • Neuroanatomy and Nomenclature University of Washington • Principles of Chemical Transmission • Hierarchical Approach to navigating around brain • E.g., • Neurotransmitters and Neuropeptides • GTA • Neighborhoods • Principal Streets • Smaller Streets Navigating Neuroanatomy: Cardinal Terms Sagittal • Anterior / Rostral Toward Front • Posterior / Caudal Toward Back Horizontal • Medial Middle (Axial) Coronal • Lateral Side • Dorsal Toward Back Side • Ventral Toward Front Side • Superior Upper • Inferior Lower • Proximal Near Center • Distal Toward Periphery Navigating Neuroanatomy Neuroanatomical Axes • Sagittal Plane LEFT & RIGHT or LATERAL & MEDIAL • Coronal Plane ANTERIOR & POSTERIOR or ROSTRAL & CAUDAL • Axial / Horizontal Plane SUPERIOR & INFERIOR or DORSAL & VENTRAL 1 Nomenclature • Cytoplasm • Contents of a cell Nomenclature • All contents outside of the nucleus of a membrane bound cell • Includes organelles and the cytosol • Cytosol • The semi-fluid component of a cell’s cytoplasm Nomenclature Nomenclature • Polymer • Organelle • A large compound of a number of subunits, • A specialized part of a cell monomers • Membrane-bound body found in cytoplasm of the cell that performs specific functions • Amino Acid • Nucleus • A class of organic chemical compounds that combine to build proteins • Most prominent organelle in the cell • A membrane bound structure that contains the cell’s • The monomer of proteins hereditary information and controls the cell’s growth and reproduction Nomenclature Nomenclature • Protein • Polymer composed of amino acids • Mitochondria • Bodies found in the cytoplasm where aerobic • Enzyme processes takes place • Protein catalyst that accelerates certain chemical reactions • Endoplasmic reticulum (ER) • Any of several complex proteins that are produced • An organelle responsible for protein synthesis by cells and act as catalysts in specific biochemical reactions • Ribosome • Site of protein synthesis • Found in cytoplasm, ER, and mitochondria 2 Nomenclature Nomenclature • Nucleotide • Deoxyribonucleic Acid (DNA) • The monomer of nucleic acids • The king of molecules • Associated with the transmission of genetic information • Nucleic Acid • A nucleic acid found in the nucleus • A polymer of nucleotides • Ribonucleic Acid (RNA) • Plays an important role in protein synthesis • A nucleic acid found in the nucleus and cytoplasm Nomenclature Nomenclature • Gene • Polymerase • In DNA, a sequence of nucelotides that contain • Enzyme that catalyzes the synthesis of nucleic acids information necessary for the metabolism and from an existing strand of DNA or RNA structure of an organism • i.e., assembling RNA from ribonucleotides or DNA from deoxyribonucleotides • Chromosome • Threadlike body in nucleus that carries the genes in a • Adenylate cyclase linear order • An enzyme that catalyses cAMP from ATP • Growth Factor • A protein involved in cell differentiation and growth Nomenclature Nomenclature • Transcription Factor • Active Transport • Any factor that controls the process of transcription (making of an RNA copy of a DNA segment). • The forced pumping of molecules from one side of a membrane to other • Usually it is some sort of enzyme or other protein, or some other sort of organic molecule. • Molecule located in membrane • Gene expression • Ion channel • Conversion (transcription) of information encoded in • A protein imbedded in a cell membrane that serves a gene first into messenger RNA and then as a crossing point for the regulated transfer of a (translated) into a protein specific ion or group of ions across the membrane. 3 Nomenclature Nomenclature • Adenosine triphosphate (ATP) G-Protein • • A cofactor that contributes either energy or a • A protein embedded in the cytoplasmic membrane of phosphate group or both to a reaction the cell that transmits signals from outside the cell to • as it does so, it loses either one or two of three the inside of the cell phosphate groups, becoming either ADP or AMP • Causes biochemical reaction within the cell, e.g., gene expression • Guanosine triphosphate (GTP) • serves as an energy source for many biochemical • Second Messenger reactions • An effector molecule that is synthesized in a cell in • during translation and is required for ribonucleic response to a signaling first messenger acid synthesis since it is a direct precursor Nomenclature Nomenclature • Phosphorylation • Neuropeptide • The addition of a phosphate group to a compound • A member of a class of protein-like molecules made • This is usually achieved by transferring a phosphate in the brain group from ATP • short chains of amino acids, with some functioning as neurotransmitters and some functioning as • Protein Kinase hormones. • An enzyme that adds phosphate groups to a protein molecule Cells in the Central Nervous System Anatomy of the Neuron • Glial cells • Mechanical and metabolic support for neurons • Cell Body (Soma) • Dendrites (Branchlike Extensions) • Neurons (nerve cells) • Dendritic Spines • Basic units of structure and function in the nervous • Axon Hillock (Signal begins) system • Synaptic terminals (Boutons) • Brain cell, and hence with DNA, nucleus, • Myelin Sheath (Glia) mitochondria (energy generating components of the • Synapse (Gap between dendrite/axon) cell), etc. 4 The Basic Structure of the Neuron The Resting Membrane Potential • Boundary of the neuron is known as the cell membrane • Voltage difference between inside and outside of the membrane (-70 mV relative to outside) • High [Na+] outside • High [K+] inside • Na+/K+ pump — active maintenance of gradient • Permeability at rest: • K+ YES • Na+ NO The Action Potential Phases of the Action Potential • Na+ & K+ flow through ion channels • If ‘threshold’ is reached….. • Ion channel opening • AP is ‘all or none’ response • all or none • Self Propogating • -70 mV to +50 mV transient • Phases • Electrical charge is redistributed across membrane • Rising to threshold • Membrane becomes ‘depolarized’ • Depolarization • Repolarization • Hyperpolarization Importance of action potential to NT Electrical versus Chemical Synapses neurotransmission Electrical Synapses Chemical Synapses • Impulse from AP opens ion channels for Ca2+ Rapid bidirectional transmission Slow unidirectional transmission • The increased Ca2+ concentration in the axon terminal initiates the release of the neurotransmitter (NT) Gap junctions Presynaptic vesicles, active zones, • NT is released from its vesicle and crosses the “gap” or postsynaptic receptors synaptic cleft and attaches to a protein receptor on the dendrite Ion current Chemical neurotransmitters • Interaction of NT and protein receptor open post- synaptic membrane ion channel for Na+ • After transmission the NT is either degraded by an Electrotonic transmission Complex amplifying enzyme or taken back into the pre-synaptic membrane excitatory/inhibitory signals by a transporter or reuptake pump Cytoplasmic continuity Synaptic cleft 5 Principles of Chemical Neurotransmission Chemical Transmission • Understanding of synaptic transmission is necessary to understand the causes of mental disorders and the actions of psychoactive drugs • Piggy-back on preexisting infrastructure because NTs are endogenous signaling molecules that alter the behaviour of neurons or effector cells • The properties of the NTs do NOT determine its effects on the the postsynaptic cell, but rather the receptor determines whether a NT is excitatory or inhibitory Chemical Synapses Chemical Transmission • Specialized junction that transfers nerve impulse information from a presynaptic membrane to a postsynaptic membrane using neurotransmitters and • Slower than electrical and generally unidirectional enzymes • Integrative • Amplifies and regenerates the signal Principle of the Synapse Anatomy of the Synapse • The Synapse • Organized to send synaptic information to other • Point where two cells meet to transfer signal from neurons one neuron to another neuron or effector • AXON • Chemical event • Primarily unidirectional communication between neurons • Organized to receive synaptic information from other neurons • Synaptic Cleft • DENDRITE • 20-50 nm wide • CELL BODY • Prevent impulses from directly passing from one • AXON neuron to another 6 Anatomy of the Synapse Anatomy of the Synapse • Synaptic Bouton (Presynaptic Terminal) • Membrane Differentiations • Contains synaptic vesicles (~50 nm in diameter) • accumulations of proteins on either side of the synaptic cleft • Contains synaptic granules (~100 nm in diameter) called large dense core vesicles • Active Zones • presynaptic side of neurotransmitter (NT) release • Postsynaptic Density • contains receptors to translate NT into intracellular signal ELECTRON MICROGRAPHS OF A SYNAPSE The Synapse Function of the Synapse • Receive information in the form of action potentials • Axon from the presynaptic neuron joins the • Electrical impulses traveling down the axon postsynpatic neuron at either a dendrite or a cell body • Can be multiple neurons interacting at the synapse • Presynaptic Neuron conducts impulses toward the • Simply pass on the same information received onto the synapse next neuron • SIGNAL • Block transmission from one neuron to the next • Postsynaptic Neuron transmits impulses away from the synapse • RECEIVER