Neurohistology: part 1 1 Med I Neural Science Andy Fischer, Ph.D. Department of Neuroscience

Learning objectives: 2 Learning Objectives: (1) Identify the different classes of cell types in the CNS (2) Describe the key cellular features that distinguish neurons from glial cells (3) Describe the key cellular features that distinguish astrocytes from oligodendrocytes (4) Describe the different parts of a neuron (5) Describe the functions of the different parts of a neuron (6) Describe the importance of axonal transport (7) Describe the importance of myelination of axons

Outline 3 Histology of the Nervous system Part 1 Neuron Parts of a neuron – dendrite & spines - cell body - axons - axon terminals & synapses Glia Astrocytes Oligodendrocytes & Schwann cells Microglia

The neuron 4 The Neuron is the Functional Unit of the Nervous System Neurons have Dendrites (with Postsynaptic Terminals) Cell Body (Soma, Perikaryon) Axon (with Presynaptic Terminals) Electrical current flows from dendrites to axon.

Dendrites 5 Dendrites (dendritic fields) come in many shapes and sizes

Dendritic spines 6 Dendrites can have numerous spines Cajal, 1917 J.M. Mateos & B. Stierli. U of Zurich M. Sheng, RIKEN-MIT Neurosci Res Center Spines are dynamic structures and the abundance of these structures on a dendrite represents “synaptic strength”

Spines are dendritic specializations 7 Spines are Dendritic Specializations Synapses are frequently found on dendritic spines. The synaptic active zone is indicated by a red arrow placed on the presynaptic element.

The neuronal cell body 8 Neuron: Cell Body Golgi stain (silver impregnation) used to randomly label cells in the cortex; pyramidal neuron (P) and astrocytes (A). GFP-transgene delivered randomly to label a retinal ganglion cell

The cell body cont’d 9 Neuron: Cell Body Electron micrograph of a neuronal cell body with dendrites to the top, right and bottom right (red arrows). No axon from this cell body seen in this micrographs. The nucleus contains euchromatin (light) and a little heterochromatin (dark). Note the extensive endoplasmic reticulum (areas of gray) in the cytoplasm – indicating a significant capacity for synthesis. The white circles are blood vessels.

Most of the neurons’ cytoplasm is in the axon 10 Neuron: Cell Body Extensive endoplasmic reticulum within the cell body of a projection neurons indicates the need for significant biosynthetic machinery to support a huge, relative volume of cytoplasm within the axon The cell body of a neuron can comprise less than one percent of the entire cell volume

The axon hillock 11 The axon hillock or axon initial segment Electrical current flows from dendrites to axon. The “decision” to send a signal (action potential) to a post-synaptic target is made at the axon hillock.

The axon hillock cont’d 12 AH = Axon Hillock IS = Initial Segment Red Arrow = Myelin Neuron: Axon

The axon 13 Neuron: Axon Electron micrograph of a neuronal cell body with and axon to the bottom. Extensive accumulations of ribosomes are seen in the cell body. The abundance of ribosomes are diminished as the axons initial segment forms (red arrow). Note: the ribosomes are the little black dots

Axons have different diameters 14 Axons have different diameters ….why is that?

Axon diameters and conduction velocities 15 Physical and Physiological Grouping of Axons Note: diameter of axon and myelination determine conduction velocity 120 m/s = 350 mph, 1 m/s = 2 mph

Axon terminals 16 Axon terminals: Neuromuscular junction Axon terminal in spinal cord Note: axons can form co-laterals and establish terminal arbors to contact multiple targets

The synapse 17 Axon Specialization: Synapse A Synapse is formed by two different neurons. The presynaptic element (above) is an axon terminal, and the postsynaptic element (below) is a dendrite. The extracellular space between is called synaptic cleft.

Types of neurons 18 Neuron Shapes Bipolar single (short) axon and dendrite (interneuron) Pseudo-unipolar only axons (sensory neuron) A pseudo-unipolar neuron has an axon, but no dendrites that receive input from other neurons. The size and shape of the dendritic field and axonal organization are important in neuronal function.

Types of neurons cont’d 19 Neuron Shapes Multipolar (three examples shown) Short dendrites (spinal motor neuron) Long dendrites (hippocampal neuron) Numerous dendrites (Purkinjie cell) Neurons with short axons that remain local (within 10’s of microns of the cell body) are interneurons. Neurons with long axons (i.e. 0.1 to 100cm) that connect to different regions of the nervous system are projection neurons.

Glia: astrocytes 20 Glia Glia are the supporting cells of the nervous system. There are several types of Glia: astrocytes, oligodendrocyte, Schwann cell, & microglia Astrocytes: Found only in CNS Regulate ions and pH Take-up neuroactive compounds (neurotransmitters) End feet carry material to and from capillaries Structural support (many intermediate filaments)

Astrocytes cont’d 21 Glia: Astrocytes Astrocytes Fibrous Protoplasmic Astrocyte Types Fibrous in white matter Protoplasmic in gray matter Astrocytes have a unique intermediate filament type, glial fibrillary acidic protein (GFAP).

Astrocytes cont’d 22 Glia: Astrocytes Astrocytes have a unique intermediate filament type, glial fibrillary acidic protein (GFAP). GFAP immunofluorescence in vitro GFAP immunolabeling in a section of the brain

Astrocytes cont’d 23 Glia: Astrocytes Astrocyte Types A. Protoplasmic astrocytes and blood vessels (black arrow indicates a microglial cell). B. Fibrous astrocytes C. Oligodendrocyte D. Microglia

Myelinating glia 24 Glia: Myelination Schwann cell - myelinating cell of the PNS Oligodendrocyte - myelinating cell of the CNS Each Schwann cell wraps only one axon segment. Each oligodendrocyte wraps multiple segments. Myelin is an insulating wrapping of axons Myelin extends for short axonal segments between Nodes of Ranvier. The myelinated portion of the axon is called an internodel segment. Function = increased rates of conduction.

Myelin wrapping an axon 25 A cell process wraps the axon (A inside circle) bringing the plasma membranes close together. Compaction pushes out the cytoplasm. Glia: Myelination

The Oligodendrocyte cont’d 26 Glia: Oligodendrocyte Electron micrograph

The Schwann cell 27 Schwann cell wrapping an axon (red asterisks ). Numerous wraps of the Schwann cell membrane form the myelin sheath * Glia: Schwann cell

The node of Ranvier 28 Glia: Nodes of Ranvier Each myelin sheath ends (red arrows) and where another begins the space is called a node of Ranvier. Action potentials jump from node to node for rapid conduction. Axons exposed at the nodes have accumulations of voltage gated sodium channels.

Microglia 29 Glia: Microglia Found in CNS, in both white and gray matter. Microglia are scavenging cells, that phagocytose debris when damaged. Microglia are derived from circulating macrophages, and are resting (quiescent) in the normal nervous system.

Quiescent vs reactive microglia 30 Glia: Microglia Quiescent vs “activated” ramified vs ameboid morhpology

31 (1) What is the purpose of the myelin sheath? (2) How are microglia different from astrocytes? (3) What are the differences between oligodendrocytes and schwann cells? (4) What are the differences between projection and inter neurons? (5) What are the differences between dendrites and axons? (6) What is the purpose of the axon initial segment? (7) Where on neuron are post-synaptic terminals formed? Practice Questions

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