CSE511 Brain & Memory Modeling. Lect03: Intro to Neuroscience

Transcription

1 CSE511 Brain & Memory Modeling CSE511 Brain & Memory Modeling Lect02: BOSS Discrete Event Simulator Lect03: Intro to Neuroscience Chapter 1 of Purves et al., 4e Larry Wittie Computer Science, StonyBrook University and ~lw 1

2 Figure 1.1 Estimated number of genes in four animal genomes Figure 1.1 Estimated number of genes in the human genome, as well as in the genomes of the mouse, the fruit fly Drosophila melanogaster, and the nematode worm Caenorhabditis elegans. Note that the number of genes does not correlate with organismal complexity; the simpler nematode has more genes than the fruit fly and current analysis indicates that mice and humans actually have about the same number (25,000) of genes. Much genetic activity is dependent on transcription factors that regulate when and to what degree a given gene is expressed. 2

3 Figure 1.2 Some nerve cell morphologies found in the human nervous system Figure 1.2 Examples of the rich variety of nerve cell morphologies found inthe human nervous system. Tracings are from actual nerve cells stained by impregnation with silver salts (the so-called Golgi technique, the method used in the classical studies of Golgi and Cajal). Asterisks indicate that the axon runs on much farther than shown. Note that some cells, like the retinal bipolar cell, have a very short axon, and that others, like the retinal amacrine cell, have no axon at all. The drawings are not all at the same scale. The following slides show image details. 3

4 Figure 1.2 Some nerve cell morphologies found in the human nervous system (Part 1) Cranial nerves (A) originate in the midbrain, pons, and medulla at the base of the brain just above the spinal cord. (See Appendix Figure A7.) The three types of retinal cells (B-D) shown are found in the five neuronal layers at the back of each eye. (The receptor and horizontal cells of the retina are not shown. See Vision Figure 11.5.) 4

5 Figure 1.2 Some nerve cell morphologies found in the human nervous system (Part 2) 5

6 Figure 1.3 The major light and electron microscopical features of neurons Figure 1.3 The major light and electron microscopical features of neurons. (A) Diagram of nerve cells and their component parts. (B) Axon initial segment (blue) entering a myelin sheath (green). (C) Terminal boutons (blue) loaded with synaptic vesicles (arrowheads) forming synapses (arrows) with a dendrite (purple). (D) Transverse section of axons (blue) ensheathed by the processes of oligodendrocytes (gold). (E) Apical dendrites (purple) of cortical pyramidal cells. (F) Nerve cell bodies (purple) occupied by large round nuclei. (G) Portion of a myelinated axon (blue) illustrating the intervals between adjacent segments of myelin (gold) referred to as nodes of Ranvier (arrows). (Micrographs from Peters et al., 1991.) The following slides show image details. 6

7 Figure 1.3 The major light and electron microscopical features of neurons (Part 1) (A) The major components of the soma of a typical neuron plus its proximal axon and dendrites amid a background of dendrites, somas, and axons of other neurons. The regions labeled B to G are each shown in electron-micrographic detail in the following slides. 7

8 Figure 1.3 The major light and electron microscopical features of neurons (Part 2) B shows an (output) axon; C, terminal boutons at the ends of two axons that form side-by-side synapses onto one dendrite; D, cross sections through five myelinated axon(s), showing the spiral of oligodendrocytic glial membranes insulating each axon; 8

9 Figure 1.3 The major light and electron microscopical features of neurons (Part 3) E shows several branching segments of (input) dendrites for a nearby neuron; F, the soma (cell body) of another neuron with its large central nucleus full of DNA; and G, a myelinated axon showing a gap (node of Ranvier) between two insulating glial membranes where active exchanges of extracellular Na + and intracellular K + ions amplify firing spikes as they rapidly propagate along lengthy axons. 9

10 Figure 1.4 Distinctive arrangement of cytoskeletal elements in neurons Figure 1.4 Distinctive arrangements of cytoskeletal elements in neurons. (A) The cell body, axons, and dendrites are distinguished by the distribution of tubulin (green throughout cell) versus other cytoskeletal elements-in this case, the microtubule-binding protein Tau (red), which is found only in axons. (B) The localization of actin (red) to the growing tips of axonal and dendritic processes is shown here in a cultured neuron taken from the hippocampus. (C) In contrast, in a cultured epithelial cell, actin (red) is distributed in fibrils that occupy most of the cell body. (D) In astroglial cells in culture, actin (red) is also seen in fibrillar bundles. (E) Tubulin (green) is seen throughout the cell body and dendrites of neurons. (F) Although tubulin is a major component of dendrites, extending into spines, the head of the spine is enriched in actin (red). (G) The tubulin component of the cytoskeleton in non-neuronal cells is arrayed in filamentous networks. (H-K) Synapses have a distinct arrangement of cytoskeletal elements, receptors, and scaffold proteins. (H) Two axons (green; tubulin) from motor neurons are seen issuing two branches each to four muscle fibers. The red shows the clustering of postsynaptic receptors (in this case for the neurotransmitter acetylcholine). (I) A higher power view of a single motor neuron synapse shows the relationship between the axon (green) and the postsynaptic receptors (red). (J) Proteins in the extracellular space between the axon and its target muscle are labeled green. (K) Scaffolding proteins (green) localize receptors (red) and link them to other cytoskeletal elements. The scaffolding protein shown here is dystrophin, whose structure and function are compromised in the many forms of muscular dystrophy. (A courtesy of Y. N. Jan; B courtesy of E. Dent and F. Gertler; C courtesy of D. Arneman and C. Otey; D courtesy of A. Gonzales and R. Cheney; E from Sheng, 2003; F from Matus, 2000; G courtesy of T. Salmon et al.; H-K courtesy of R. Sealock.) 10

11 Figure 1.4 Distinctive arrangement of cytoskeletal elements in neurons (Part 1) (A) The cell body, axons, and dendrites are distinguished by the distribution of tubulin (green throughout cell) versus other cytoskeletal elements - in this case, the microtubule-binding protein Tau (red), which is found only in axons. (B) The localization of actin (red) to the growing tips of axonal and dendritic processes is shown here in a cultured neuron taken from the hippocampus. (C) In contrast, in a cultured epithelial (e.g., skin) cell, actin (red) is distributed in fibrils that occupy most of the cell body. (D) In astroglial cells in culture, actin (red) is also seen in fibrillar bundles. (A courtesy of Y. N. Jan; B courtesy of E. Dent and F. Gertler; C courtesy of D. Arneman and C. Otey; D courtesy of A. Gonzales and R. Cheney.) 11

12 Figure 1.4 Distinctive arrangement of cytoskeletal elements in neurons (Part 2) (E) Tubulin (green) is seen throughout the cell body and dendrites of neurons. (F) Although tubulin is a major component of dendrites, extending into the spines, the head of each spine is rich in actin (red). (G) The tubulin component of the cytoskeleton in non-neuronal cells is arrayed in filamentous networks. (E from Sheng, 2003; F from Matus, 2000; G courtesy of T. Salmon et al.) 12

13 Figure 1.4 Distinctive arrangement of cytoskeletal elements in neurons (Part 3) (H) Two axons (green; tubulin) from motor neurons are seen issuing two branches each to four muscle fibers. The red shows the clustering of postsynaptic receptors (in this case for the neurotransmitter acetylcholine). (I) A higher power view of a single motor neuron synapse shows the relationship between the axon (green) and the postsynaptic receptors (red). (J) Proteins in the extracellular space between the axon and its target muscle are labeled green. (K) Scaffolding proteins (green) localize receptors (red) and link them to other cytoskeletal elements. The scaffolding protein shown here is dystrophin, whose structure and function are compromised in the many forms of muscular dystrophy. (H-K courtesy of R. Sealock.) 13

14 Figure 1.5 Varieties of neuroglial cells Figure 1.5 Varieties of neuroglial cells. Tracings of an astrocyte (A), an oligodendrocyte (B), and a microglial cell (C) visualized using the Golgi method. The images are at approximately the same scale. (D) Astrocytes in tissue culture, labeled (red) with an antibody against an astrocyte-specific protein. (E) Oligodendroglial cells (green) in tissue culture labeled with an antibody against an oligodendroglial-specific protein. (F) Peripheral axons are ensheathed by myelin (labeled red) except at nodes of Ranvier (see Figure 1.3G). The green label indicates ion channels concentrated in the node; the blue label indicates a molecularly distinct region called the paranode. (G) Microglial cells from the spinal cord, labeled with a cell type-specific antibody. Inset: Higher-magnification image of a single microglial cell labeled with a macrophageselective marker. (A-C after Jones and Cowan, 1983; D, E courtesy of A.-S. LaMantia; F courtesy of M. Bhat; G courtesy of A. Light; inset courtesy of G. Matsushima.) 14

15 Figure 1.5 Varieties of neuroglial cells (Part 1) Tracings of an astrocyte (A), an oligodendrocyte (B), and a microglial cell (C) visualized using the Golgi method. Like macrophages in the blood, microglial cells in the nervous system are scavengers of damaged cell parts. The three images of glia are at approximately the same scale. (A-C after Jones and Cowan, 1983.) 15

16 Figure 1.5 Varieties of neuroglial cells (Part 2) (D) Astrocytes in tissue culture, labeled (red) with an antibody against an astrocyte-specific protein. (E) Oligodendroglial cells (green) in tissue culture labeled with an antibody against an oligodendroglial-specific protein. (F) Peripheral axons are ensheathed by myelin (labeled red) except at nodes of Ranvier (see Figure 1.3G). The green label indicates ion channels concentrated in the node; the blue label indicates a molecularly distinct region called the paranode. (G) Microglial cells from the spinal cord, labeled with a cell type-specific antibody. Inset: Higher-magnification image of a single microglial cell labeled with a macrophage-selective marker. (D, E courtesy of A.-S. LaMantia; F courtesy of M. Bhat; G courtesy of A. Light; inset courtesy of G. Matsushima.) 16

17 Figure 1.6 Visualizing nerve cells and their connections Figure 1.6 Visualizing nerve cells and their connections. (A) Cortical neurons stained using the Golgi method (impregnation with silver salts). (B) Golgi-stained Purkinje cells in the cerebellum. Purkinje cells have a single, highly branched apical dendrite. (C) Intracellular injection of fluorescent dye labels two retinal neurons that vary dramatically in the size and extent of their dendritic arborizations. (D) Intracellular injection of an enzyme labels a neuron in a ganglion of the autonomic (involuntary) nervous system. (E) The dye cresyl violet stains RNA in all cells in a tissue, labeling the nucleolus (but not the nucleus) as well as the ribosome-rich endoplasmic reticulum. Dendrites and axons are not labeled, explaining the "blank" spaces between neurons. (F) Nissl-stained section of the cerebral cortex, showing cell bodies arranged into layers of differing cell densities. (G) Higher magnification of one area of cerebral cortex shows that differences in cell density define boundaries between layers of this visual cortex. (H) Nissl stain of the olfactory bulbs reveals a distinctive distribution of cell bodies, particularly those cells arranged in rings on the outer surface of the bulb. These structures, including the cell-sparse tissue contained within each ring, are called glomeruli. (C courtesy of C. J. Shatz; all others courtesy of A.-S. LaMantia and D. Purves.) 17

18 Figure 1.6 Visualizing nerve cells and their connections (Part 1) Figure 1.6 Visualizing nerve cells and their connections. (A) Cortical neurons stained using the Golgi method (impregnation with silver salts). (B) Golgi-stained Purkinje cells in the cerebellum. Purkinje cells have a single, highly branched apical dendrite. (C) Intracellular injection of fluorescent dye labels two retinal neurons that vary dramatically in the size and extent of their dendritic arborizations. (D) Intracellular injection of an enzyme labels a neuron in a ganglion of the autonomic (involuntary) nervous system. (C courtesy of C. J. Shatz; all others courtesy of A.-S. LaMantia and D. Purves.) 18

19 Figure 1.6 Visualizing nerve cells and their connections (Part 2) (E) The dye cresyl violet stains RNA in all cells in a tissue, labeling the nucleolus (but not the nucleus) as well as the ribosome-rich endoplasmic reticulum. Dendrites and axons are not labeled, explaining the "blank" spaces between neurons. (F) Nissl-stained section of the cerebral cortex, showing cell bodies arranged into layers of differing cell densities. (G) Higher magnification of one area of cerebral cortex shows that differences in cell density define boundaries between layers of this visual cortex. (H) Nissl stain of the olfactory bulbs reveals a distinctive distribution of cell bodies, particularly those cells arranged in rings on the outer surface of the bulb. These structures, including the cell-sparse tissue contained within each ring, are called glomeruli. (All E-H courtesy of A.-S. LaMantia and D. Purves.) 19

20 Figure 1.7 A simple reflex circuit, the knee-jerk response Figure 1.7 A simple reflex circuit, the knee-jerk response (more formally, the myotatic reflex), illustrates several points about the functional organization of neural circuits. Stimulation of peripheral sensors (a muscle stretch receptor in this case) initiates receptor potentials that trigger action potentials that travel centrally along the afferent axons of the sensory neurons. This information stimulates spinal motor neurons by means of synaptic contacts. The action potentials triggered by the synaptic potential in motor neurons travel peripherally in efferent axons, giving rise to muscle contraction and a behavioral response. One of the purposes of this particular reflex is to help maintain an upright posture in the face of unexpected changes. Adapted from: 20

21 Figure 1.8 Relative frequency of action potentials in different components of the myotatic reflex Figure 1.8 Relative frequency of action potentials, also called firing spikes, (indicated by individual vertical lines) in different components of the myotatic reflex as the reflex pathway is activated. Notice the modulatory effect of the inhibitory interneuron, shown in purple. The circuit keeps the opposing forces of the extensor and flexor muscles balanced. See figure 1.9 for more details on action potentials. 21

22 Figure 1.9 Intracellularly recorded responses underlying the myotatic reflex Figure 1.9 Intracellularly recorded responses underlying the myotatic reflex. (A) Action potential measured in a sensory neuron. (B) Postsynaptic triggering potential recorded in an extensor motor neuron. (C) Postsynaptic triggering potential in an inhibitory interneuron. (D) Postsynaptic inhibitory potential in a flexor motor neuron. Intracellular recordings like these are the basis for understanding the cellular mechanisms of action potential generation, and the sensory receptor and synaptic potentials that trigger these conducted signals. 22

23 Figure 1.10 The major components of the nervous system and their functional relationships Figure 1.10 The major components of the nervous system and their functional relationships. (A) The CNS (brain and spinal cord) and PNS (spinal and cranial nerves). (B) Diagram of the major components of the central and peripheral nervous systems and their functional relationships. Stimuli from the environment convey information to processing circuits within the brain and spinal cord, which in turn interpret their significance and send signals to peripheral effectors that move the body and adjust the workings of its internal organs. 23

24 Figure 1.11 Cellular and molecular approaches for studying connectivity and molecular identity of nerve cells (Part 1 tracing connections) Figure 1.11a Tracing connections and pathways in the brain. (A) Radioactive amino acids can be taken up by one population of nerve cells (in this case, injection of a radioactively labeled amino acid into one eye) and be transported to the axon terminals of those cells in the target region in the brain. (B) Fluorescent molecules injected into nerve tissue are taken up by the axon terminals at the site of the injection. The molecules are then transported, labeling the cell bodies and dendrites of the nerve cells that project to the injection site. (C) Tracers that label axons can reveal complex pathways in the nervous system. In this case, a dorsal root ganglion has been injected, showing the variety of axon pathways from the ganglion into the spinal cord. (A courtesy of P. Rakic; B courtesy of B. Schofield; C courtesy of W. D. Snider and J. Lichtman.) 24

25 Figure 1.11 Cellular and molecular approaches for studying connectivity and molecular identity of nerve cells (Part 2 molecular differences) Figure 1.11b Molecular differences among nerve cells. (D) A single glomerulus in the olfactory bulb (see Figure 1.6H) has been labeled with an antibody against the inhibitory neurotransmitter GABA. The label shows up as a red stain, revealing GABA to be localized in subsets of neurons around the glomerulus as well as at synaptic endings in the neuropil of the glomerulus. (E) The cerebellum has been labeled with an antibody that recognizes subsets of dendrites (green). (F) Here the cerebellum has been labeled with a probe (blue) for a specific gene that is expressed only by Purkinje cells. (D-F courtesy of A.-S. LaMantia, D. Meechan and T. Maynard.) 25

26 Figure 1.12 Use of genetic engineering to show pathways within the nervous system Figure 1.12 Genetic engineering is used to show pathways within the nervous system. A "reporter gene" that codes for some visualizable substance (e.g., green fluorescent protein, GFP) is inserted into the genome under the control of a cell type-specific promoter (a DNA sequence that turns the gene "on" in specific tissue and cell types). The reporter is expressed only in those cell types, revealing the cell bodies, axons, and dendrites of all cells in the nervous system that express the gene. Here the reporter is under the control of a promoter DNA sequence that is activated only in a subset of dorsal root ganglion neurons. Photographs show that the reporter labels neuronal cell bodies; the axons that project to the skin as free nerve endings; and the axon that projects to the dorsal root of the spinal cord to relay this sensory information from the skin to the brain. (Photographs from Zylka et ai., 2005.) 26

27 Figure 1.13 Single-unit electrophysiological recording from cortical pyramidal neuron Figure 1.13 Single-unit electrophysiological recording from a cortical pyramidal neuron, showing the firing pattern in response to a specific peripheral stimulus. (A) Typical experiment set-up, in which a recording electrode is inserted into the somatic sensory neocortex region of the brain. (B) Defining neuronal receptive fields by brushing many locations on the skin of a monkey s arm. 27

28 Box 1A(1) Brain Imaging Techniques Box 1A(1) In computerized tomography (CT), the X-ray source and detectors are moved around the patient's head. The inset shows a horizontal CT section of a normal adult brain. 28

29 Box 1A(2) Brain Imaging Techniques Box 1A(2) In MRI (magnetic resonance imaging) scanning, the head is placed in the center of a powerful magnet. A radio-frequency antenna coil is placed around the head for exciting and recording the magnetic resonance signal. For fmri (functional MRI), stimuli can be presented using virtual reality video goggles and stereo headphones while inside the scanner. 29

30 Box 1A(3) Brain Imaging Techniques Box 1A(3) MRI images of an adult patient with a brain tumor, with fmri activity during a hand motion task superimposed (left hand activity is shown in yellow, right hand activity in green). At right is a three-dimensional surface reconstructed view of the same data. Note that left hand movement is controlled by the right cerebral hemisphere. The resolutions of fmri are much too poor to image single neurons mm spatially (roughly 0.2 to 6 million neurons) and 3-5 seconds temporally. 30