MS-1 FUND 1: 11:10-12:00 Monday, September 15, 2014 Dr. Cotlin Nerve Tissue Transcriber: Katherine Shelton Editor: Travis Atchley Page 1 of 4 Abbreviations: ANS – autonomic nervous system, CT – connective tissue, CNS – central nervous system, PNS – peripheral nervous system Introductory Comments: This transcript is for the second hour of Dr. Cotlin’s lecture on Nerve Tissue. Clarification from previous lecture: When touching a hot object and recoiling, the signal travels back to the CNS. It is incorrect to say that the signal goes back to the brain, because many signals go only to the spinal cord. I. Myelinated Nerve Fibers (continued from first hour) 4:08 a. A Peripheral Nerve and its Myelin Sheath (slide 38) i. Clarification – myelin sheath refers to the layers of membrane formed by wrapping of Schwann cells ii. Multiple cells lie along each axon, interact as gaps between cells called nodes of Ranvier b. Myelin Sheath and Node of Ranvier (slide 39) 4:25 i. Shmidt-Lanterman cleft – a wave of bulging from the wrapped layers (not important to know) ii. Myelin sheath contains layers of cytoplasm between wrapped Schwann cell membrane 1. Lipid rich due to multiple lipid bilayers; doesn’t contain specialized lipid c. Electron Micrograph of Node of Ranvier (slide 40) 5:15 i. Node of Ranvier is an area with no myelin sheath ii. Not apparent as a bare area because some infolding of Schwan cells exists, just a space with less prominent myelin d. Structure and Components at the Nodes (slide 41) 5:36 i. Nodes of Ranvier house channels responsible for action potentials 1. Voltage-gated Na+ channels (stained green in image) are primary channels involved in generating action potentials and are found concentrated at nodes, not along length of axons 2. Voltage-gated K+ channels (stained blue) are in nodes but are also found throughout axons ii. Caspr (stained red) – node junctional protein that exists on sides of each node, restricting movement of voltage-gated channels and sequestering them in one area 1. Provides electrical seal e. Action Potential Triggered by Depolarization of Membrane (slide 42) 6:56 i. Graph shows membrane potential as voltage-gated Na+ channels open, inactivate, and close ii. Nodes of Ranvier allow rapid transmission of action potential; can skip lengths of axon and propagate node-to-node f. Propagation of an Action Potential (slide 43) 7:44 i. Channels begin closed, then open and subsequently inactivate. 1. The inactivation of channels allows action potentials to propagate in only one direction 2. Action potentials always propagate from soma to axon terminal; cannot move backwards g. Nodes of Ranvier – H&E Stain – the nodes appear as “pinched in” areas on the stain (slide 44) 8:34 II. Unmyelinated fibers a. Structure of an Unmyelinated Nerve Fiber (slide 45) 8:42 i. Unmyelinated fibers are not totally bare, just lacking a fully wrapped sheath ii. Still associated with Schwann cells, just not completely wrapped 1. One Schwan cell associates with several unmyelinated axons b. Unmyelinated Axons (slide 46) 9:15 i. First, a neurolemmocyte (another name for Schwann cell) starts to envelop multiple axons ii. The unmyelinated axons are enveloped, but no myelin sheaths are wrapped around individual axons c. Example of myelinated vs. unmyelinated axons (slide 48) 9:27 i. Nuclei of Schwann cells are visible hanging off of myelinated axons ii. Unmyelinated axons are present in groups with their associated Schwann cell III. ARS questions a. 9:53: Calcium is the major mediator at axon terminals, whereas sodium is the mediator along axons. To decrease release of neurotransmitter, blocking calcium influx would be useful. b. 10:34 Nerve cell bodies are not present in peripheral nerves. These nerves are made of axons only and have associated Schwann cells, fibroblasts, and blood vessels. IV. Peripheral Nerves a. Organization of Neurons in a Peripheral Nerve (slide 49) 11:31 i. A peripheral nerve is a bundle of many different types of neurons The nerve pictured contains 1. Somatic sensory neurons receiving input from Pacinian corpuscles (sensory organ of skin) 2. Autonomic unmyelinated neurons receiving signals from enteroceptors of the ANS and sending signals to smooth muscle 3. Somatic motor neurons sending signals to striated muscle ii. Nerves have CT coating similar to muscle fibers iii. Nerves also contain blood vessels b. Histology of Peripheral Nerves (slide 50) 13:53 MS-1 FUND 1: 11:10-12:00 Monday, September 15, 2014 Dr. Cotlin Nerve Tissue Transcriber: Katherine Shelton Editor: Travis Atchley Page 2 of 4 Abbreviations: ANS – autonomic nervous system, CT – connective tissue, CNS – central nervous system, PNS – peripheral nervous system i. Endoneurium – loose CT surrounding every nerve fiber ii. Perineurium – specialized CT surrounding each nerve fascicle iii. Epineurium – dense CT surrounding entire nerve iv. Vasa nervosa – blood vessels that penetrate surrounding CT to feed nerve cells (slide 52) v. Can be large with multiple fascicles; nerves get smaller and have finer structures with branching (slide 53) V. Peripheral Ganglia (slide 54) 15:07 a. House cell bodies of peripheral nerves outside the CNS; two types exist i. Dorsal root ganglia contain cell bodies of sensory neurons (somatic and visceral afferent). No synapses in dorsal root ganglia - processes enter and exit, but no information is transferred between cells. ii. Autonomic ganglia contain cell bodies of autonomic postsynaptic neurons. They are synaptic stations. b. Schematic of a Dorsal Root Ganglia (slide 55) 16:15 i. Comes from the dorsal surface of the spinal cord ii. Dorsal root ganglion neurons are pseudounipolar sensory neurons – signals come in from the sensory organs and pass through the ganglion without synapsing on the way to the CNS iii. The axon terminal lies past the ganglion; signal bypasses the ganglion itself c. Schematic of an Autonomic Ganglia (slide 56) 17:03 (SN: A visceral efferent neuron is used in this example, so this is in the context of information traveling from the CNS to involuntary effectors such as blood vessel and sweat gland smooth muscles) i. Autonomic ganglia come from the ventral surface of the spinal cord ii. Synapses do occur in autonomic ganglia – information is relayed from one neuron (pre-synaptic neuron) to another (post-synaptic neuron), which then synapses with the effected tissue d. Histology of Ganglia (slide 57) 21:00 i. Sensory ganglia – dorsal root/spinal ganglia 1. Pseudounipolar neurons of various sizes 2. Soma are concentrated at the periphery of the ganglion with axons running through the middle 3. Rounded perikaryon (soma), central nucleus ii. Autonomic ganglia – sympathetic or parasympathetic ganglia 1. Multipolar neurons of similar size 2. Neurons randomly distributed throughout ganglion since multipolar neurons cannot cluster as well as pseudounipolar neurons 3. Perikaryon with numerous processes 4. Eccentric nucleus iii. Common traits 1. Surrounded by satellite cells a. In the context of ganglia, satellite cells are supporting cells, not the same as satellite cells involved in muscle regeneration 2. Fibroblasts throughout secrete endoneurium iv. Example Images: 1. Dorsal root ganglion a. Soma are peripherally located and axons run through the middle of the ganglia (slide 58) b. Silver stain shows abundance of fibrous material throughout the ganglion (slide 59) c. Also shows perikaryon and centrally located nucleus of sensory ganglia cells (slide 60) d. Fibrous material is apparent with other stains (slide 61) e. Neurons, satellite cells, and fibroblasts are visible (slide 62) 2. Autonomic ganglion a. Autonomic ganglia are embedded in adipose and CT to insulate and support (slide 63) i. In contrast, dorsal root ganglia are knob protruding from nerve, not embedded in tissue b. Soma in autonomic ganglia are spread out c. Nucleus tends to be offset rather than central (slide 64) d. Parasympathetic ganglia are similar to sympathetic as they are embedded in tissue. Some are close to spine and others are closer to effector organs (slide 65, 66) (SN: Slides 63 and 64 showed sympathetic ganglia, but we will not have to distinguish between sympathetic and parasympathetic ganglia. Just know that they are both autonomic.) VI. The Central Nervous System (slide 67) 25:01 a. Spinal cord (SN: brain is also part of the CNS, but will be discussed tomorrow) b. Neuroglial cells of the CNS – supporting cells i. Astrocytes ii. Oligodendrocytes iii. Microglia iv. Ependymal cells c. Cross Section of the Spinal Cord (slide 68) 25:30 MS-1 FUND 1: 11:10-12:00 Monday, September 15, 2014 Dr. Cotlin Nerve Tissue Transcriber: Katherine Shelton Editor: Travis Atchley Page 3 of 4 Abbreviations: ANS – autonomic nervous system, CT – connective tissue, CNS – central nervous system, PNS – peripheral nervous system i. Note dorsal roots and ventral portion ii. Internal gray matter houses all cell bodies of neurons and all synapses in the spinal cord iii. External white matter contains conduits for nerves up and down spinal cord d. White and Gray Matter (slide 69) 26:06 i. White matter – peripheral substance containing tracks of myelinated and unmyelinated axons traveling to and from other parts of the spinal cord and to and from the brain ii. Gray matter contains neuronal cell bodies, neuronal processes, and neuroglia 1. Neuropil – meshwork of axonal, dendritic, and glial processes in the gray matter 2. Nuclei – functionally related groups of nerve cell bodies a. Nucleus – cluster of a group of cell bodies plus fibers and neuroglia b. Nuclei in the CNS are functional equivalents of ganglia in PNS 3. Synapses only occur in the gray matter e. Cell Bodies of Somatic and Visceral Efferent Neurons (slide 70) 27:01 i. All cell bodies start in gray matter and extend processes elsewhere f. Spinal Cord Histology (slide 71) 27:18 i. White matter is light because it has a high degree of myelination ii. White (left side of image) and gray (right) matter of the spinal cord (slide 72) 27:40 1. Large dark cell on the right is a soma, smaller cells are supporting cells 2. Black spots in white matter are axons surrounded by white myelin sheaths 3. Both have abundant blood vessels g. Neuroglial Cells in the CNS (slide 73) 28:35 i. Oligodendrocytes – responsible for myelination in CNS, similar to Schwann cells of PNS 1. Instead of whole cell wrapping axon, processes of oligodendroycte wrap around the cell ii. Astrocytes – supporting cells that fill space and maintain blood-brain barrier iii. Microglial cells – resident macrophages of CNS iv. Ependymal cells – modified epithelial cells that line cavities containing spinal fluid 1. Unique in that they don’t sit on basement membrane and have processes on both sides h. Distribution of Glial Cells in the CNS (slide 74) 29:55 i. Many glial cells look similar to neurons and pack together with them ii. Astrocytes put out foot processes along vessels, similar to and associated with pericytes i. Example images of glial cells i. Protoplasmic astrocyte in gray matter (slide 75) ii. Fibrous astrocyte in white matter (slide 76) iii. Schematic of blood-brain barrier – neuroglial cell associated with blood vessel is an astrocyte (slide 77) j. Myelination in the CNS by Oligodendrocytes (slide 78) 31:15 i. One oligodendrocyte can myelinate multiple neurons k. Microglial Cells (slide 79) 31:30 i. Primary cells for injury response in brain by producing chemoattractants capable of attracting leukocytes across blood-brain barrier ii. Interact with astrocytes to modulate immune response iii. If something affected monocyte lineage, it would affect the microglial cells l. Example of Ependymal Lining of the Spinal Canal (slide 80) m. Further examples of neuroglia (slide 81) VII. Peripheral Nerve Injury and Repair (slide 82) 32:00 a. Peripheral nerves have capacity for repair since they are axonal, soma in the CNS are more difficult to repair b. When a nerve is damaged, macrophages rush in to clear debris c. Schwann cells then proliferate rapidly, attaching to free axon end and guiding development of the axon VIII. Response to Neuronal Injury in PNS and CNS (slide 83) 33:27 a. CNS is less capable of repair because it is a protected environment; macrophages are less able to get in IX. Peripheral Neuropathy (slide 84) 33:39 a. Many things can cause peripheral neuropathy i. Trauma ii. Infection iii. Metabolic disease (ex diabetes) iv. Exogenous toxins (ex botulism, diphtheria) v. Carcinoma vi. Drugs (ex vincristine) vii. Heavy metals (ex lead, mercury) viii. Vitamin deficiency (ex B12, B6) MS-1 FUND 1: 11:10-12:00 Monday, September 15, 2014 Dr. Cotlin Nerve Tissue Transcriber: Katherine Shelton Editor: Travis Atchley Page 4 of 4 Abbreviations: ANS – autonomic nervous system, CT – connective tissue, CNS – central nervous system, PNS – peripheral nervous system b. A damaged nerve is repaired but is not as strong as before c. More nodes are present so the action potential has to “jump” more and propagates more slowly. X. ARS Question a. 34:17 A neuron of the PNS that is regenerated after damage will often exhibit more Schwann cells surrounding the axon. Student Questions Student Question 1: Where do neurons in dorsal root ganglia synapse if there are no synapses in the ganglia? 17:36 Answer: The axon terminal is past the ganglion in the spinal cord, so the signal bypasses the neurons in the ganglion itself. Student Question 2: Are there any somas outside the CNS? 18:32 Answer: The only somas outside the CNS are located in ganglia. Student Question 3: Are autonomic ganglia always efferent? 19:57 Answer: Yes – they can be sympathetic or parasympathetic, but they always relay information out from the CNS. <END OF LECTURE 34:57>