BIO 3350 - Lec 2 Neurons and Glia PDF

LECTURE 2: NEURONS AND GLIA In this lecture we will learn 1. The challenges of studying neurons experimentally 2. The cellular and morphological characteristics of neurons 3. How to classify neurons according to different schemes 4. The other cell types that...

LECTURE 2: NEURONS AND GLIA In this lecture we will learn 1. The challenges of studying neurons experimentally 2. The cellular and morphological characteristics of neurons 3. How to classify neurons according to different schemes 4. The other cell types that make up the nervous system Reading Bear, chapter 2 1 NEUROSCIENCE TODAY NEUROSCIENCE TODAY CELLS OF THE NERVOUS SYSTEM 4 CELLS OF THE NERVOUS SYSTEM 5  VISUALIZING A NEURON - CHALLENGES 1. The size A neuron: 10 to 40 µm 1/5 of what the eye can see 40-200 x Helfmann 6  VISUALIZING A NEURON - CHALLENGES 2. Obtaining nervous tissue that is sufficiently thin 7  VISUALIZING A NEURON - CHALLENGES 3. Neurons are generally colourless ? 8  THE NEURON DOCTRINE  Histology  Study of tissue structures  Nissl staining (Cresyl violet)  Stains Nissl bodies (similar to endoplasmic reticulum) in the cytoplasm Franz Nissl (1860-1919) 9  THE NEURON DOCTRINE Nissl staining only reveals part of the whole cell Golgi staining (AgNO3) reveals two parts of neurons: Soma or perikaryon or cell body Neurites: axons and dendrites Camillo Golgi 10  THE NEURON DOCTRINE Santiago Ramon y Cajal improved Golgi’s staining method Showed that neurons communicate by contact but were not in continuity Neurons adhered to the cell theory Representation of Representation of Cajal Cajal of the cortex 11 of the dentate gyrus  MICROSCOPY The Neuron Doctrine Synaptic cleft is approximately 20nm (0.02µm) Resolution of an optical microscope: approx. 0.1µm Resolution of an electron microscope : approx. 0.01nm optical optical (live…) electron reconstitution 12  PROTOTYPICAL NEURON Parts: Soma Axon Nerve terminal Dendrite Dendritic spines Nucleus Cellular membrane Cytoskeleton 13  SOMA Mitochondria Site of cellular respiration (O2) Krebs cycle ATP – cell’s energy source The human brain represents 2% of the total body mass but consumes 20% of the O2 14  AXON Axon Electric transmission of signal output 0.1 to 10 µm diameter Branches (collaterals) bifurcating at right angles (90 º) Axon hillock Axon hillock Start of the axon that emerges from the soma Site of initiation of action potentials Axon (or nerve) terminal collaterals Synaptic transmission Differences between axon and soma Nerve ER does not extend into axon terminal Protein composition of the axon is unique 15  NERVE TERMINAL (VS AXON) Differences between nerve terminals and axons No microtubules in terminal Presence of synaptic vesicle Abundance of membrane proteins Large number of mitochondria at: axon terminal mt: mitochondria DS: dendrite ves: vesicules Sp: dendritic spine Arrow: synapse 16  SYNAPSE Synaptic transmission Electric synapses Gap junctions Chemical synapses Release of neurotransmitters 17  DENDRITES “Antennae” of neurons Dendritic tree Processing of information received through synapses More than 95% of the cell surface Diameter between 0.1 µm and 3 µm Neuron (green) and synapses in contact (red) 18  DENDRITES Dendritic spines Dendrites of certain neurons are studded with small mushroom or spine-shaped structures Receive signals from nerve terminals of other neurons Postsynaptic compartment contains synaptic receptors Associated with memory and learning 19  CELL MEMBRANE Barrier that encloses the cytoplasm ~ 5nm thick Different regions of the neuron cell membrane will contain different types of membrane proteins Specific regions will have specialized functions Presynaptic membrane Postsynaptic membrane Axonal membrane Supports electrical and chemical transmission of information 20  CYTOSKELETON Internal scaffolding of neuronal membrane 21  CYTOSKELETON Not static, very dynamic Three types of filaments Microtubules Movement of organelles Railroad for molecular motors Microfilaments (actine) Dynamic change of shape Neurofilaments Support and stability 22  AXOPLASMIC TRANSPORT Anterograde From soma to nerve terminal Requires kinesins interacting with microtubules Consumes ATP Direction of anterograde kinesin axoplasmic transport … 23  AXOPLASMIC TRANSPORT Retrograde From nerve terminal to soma Requires dyneins Consumes ATP Direction of retrograde axoplasmic transport … Dynein 24 24  AXOPLASMIC TRANSPORT In neuroscience, axoplasmic transport is useful for tracing of neurons Anterograde tracing: Labels nerve terminals Phageolus Vulgaris Leucoagglutinin Dextrans DiI Retrograde tracing: Labels cells that innervate a targetted area Dextrans DiI Horseradish Peroxydase (HRP) Virus 25  AXOPLASMIC TRANSPORT Anterograde – Used to visualize the postsynaptic connections of neurons of interest – Answers the question: “A neuron speaks to who?” ? ? ? 26 Anterograde We observe the synapses that are labelled in other regions of the nervous system Neuron Synapse Injection of anterograde tracer Regions of the brain of interest Region studied 27  AXOPLASMIC TRANSPORT Anterograde Retrograde – Used to visualize the – Used to visualize the postsynaptic presynaptic neurons connections of connected to neurons neurons of interest of interest – Answers the question: – Answers the question: “A neuron speaks to “A neuron is listening who?” to who?” ? ? ? ? ? ? 28 Retrograde We observe the cell bodies that are labelled in other regions of the nervous system Neuron Synapse Injection of retrograde tracer Regions of the brain of interest Region studied 29  QUESTIONS You are studying Nucleus3350 for honours thesis. Your research supervisor proposes that you determine which neurons in the nervous system send synaptic projections to the neurons in Nucleus3350. 1. What kind of tracing, anterograde or retrograde, would you use? 2. What would you be looking for to determine which neurons send synaptic projections to the neurons in Nucleus3350? 30  QUESTION You observe under a microscope a neurite that you believe is a dendrite. Your colleague asks you why you do not think it is an axon instead? What distinguishing features would you mention to support your conclusion 31  NEURONAL CLASSIFICATION The large number of neurons in the nervous system pose a large challenge for the study of the nervous system Multiple schemes have been used to group neurons in different classes to facilitate the understanding of their roles  NEURONAL CLASSIFICATION Classification based on the number of neurites (axon and/or dendrites) Unipolar: A single neurite Bipolar: Two neurites Multipolar: Multiple neurites 33  NEURONAL CLASSIFICATION Classification based upon cell morphology… somatic Oval/spherical cells Pyramidal cells 34 Ferris Jabr; based upon reconstructions and drawings of  NEURONAL CLASSIFICATION Classification based upon morphology… dendritic # of dendrites Lengths Branching patterns 35 (201 Polavaram et al. Frontiers in Neuroanatomy  NEURONAL CLASSIFICATION Classification based upon length of axon… Golgi type I Projection neurons Golgi type II Local Neurons 36  NEURONAL CLASSIFICATION Classification based upon connectivity SPINAL CORD Sensory neurons Sensory receptors Muscle afferent Motoneurons Muscle or gland Interneurons Contact other neurons within the CNS Interneuron Motoneuron 37  NEURONAL CLASSIFICATION Classification based upon… … type of secreted neurotransmitter Cholinergic Glutamatergic GABAergic Dopaminergic Serotoninergic Others… … the function Excitatory Inhibitory Modulatory (can excite ou inhibit) N.B. Neurotransmitter ≠ function always 38  NEURONAL CLASSIFICATION MolecularTranscription classification factors Transcription factors Transcription factors involved in the development of a neuron Stem cells Neural Postmitotics Progenitors Neurons 39  NEURONAL CLASSIFICATION MolecularTranscription classification factors Transcription factors Transcription factors involved in the development of a neuron 40  IMPORTANT QUESTION Why is it important to find ways to classify neurons? Hint: How would you go about trying to understand the function of these neurons without any classification scheme? 41  GLIA Function of glia Neuronal support And…? Astrocytes Formed by many projections: star shaped Most numerous glia in the brain Fill the space between neurons Influences neurite growth Regulate ionic extracellular concentrations Shape synaptic transmission 42  MYELINATED GLIA Oligodendrocytes (CNS) Wrap around multiple axons Schwann cells (PNS) Wrap around a single axon Insulate axons 43  MYELINATED GLIA Role of myelin Insulate axons Increases the speed of electrical transmission Node of Ranvier Region where the axonal membrane is exposed, high density of sodium channels Allows for saltatory transmission 44  GLIA Microglia Phagocyte Immune system Elimination of cellular waste and dead cells Microglia Gerry Shaw Neuron 45 46  GLIA VS NEURONS Glia: Insulate Support Nourish neurons … can shape neuronal signalling Neurons Process information Sense environmental changes Communicates perceived changes to other neurons Command corporal responses 47