Neurohistology: part 1

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Med I Neural Science

Andy Fischer, Ph.D.Department of Neuroscience

fischer.412@osu.edu

Learning objectives:

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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

OutlineOutline

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Histology of the Nervous system

Part 1Neuron

Parts of a neuron – dendrite & spines- cell body - axons - axon terminals & synapses

GliaAstrocytesOligodendrocytes & Schwann cellsMicroglia

The neuron

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The Neuron is the Functional Unit of the Nervous System

Neurons haveDendrites (with Postsynaptic Terminals)Cell Body (Soma, Perikaryon)Axon (with Presynaptic Terminals)

Electrical current flows from dendrites to axon.

Dendrites

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Dendrites (dendritic fields) come in many shapes and sizes

Dendritic spines

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Dendrites can have numerous spines

Cajal, 1917

J.M. Mateos & B. Stierli. U of ZurichM. 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

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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

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Neuron: Cell BodyGolgi 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

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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

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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

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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

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AH = Axon HillockIS = Initial SegmentRed Arrow = Myelin

Neuron: Axon

The axon

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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

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Axons have different diameters….why is that?

Axon diameters and conduction velocities

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Physical and Physiological Grouping of AxonsNote: diameter of axon and myelination determine conduction velocity

Group Diameter in microns

Conduction Velocity m/sec

Function

Sensory Neurons

Ia & Ib A 13-22 80-120 Muscle spindles, Golgi tendon organs - myelinated

II A 6-12 35-75 Many sensory modalities, muscle spindles & Golgi tendon organs

III A B

1-5 5-30 Free nerve ending, fast pain, temperature

IV C 0.2-1.5 0.5-2.0 Slow pain, temperature, some mechanoreceptors, no myelin

Motor Neurons

12-20 72-120 Skeletal muscles - myelinated 2-8 12-40 Skeletal muscle within muscle

spindles sense organs 120 m/s = 350 mph, 1 m/s = 2 mph

Axon terminals

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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

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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

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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

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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

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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

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Glia: Astrocytes

AstrocytesFibrous Protoplasmic

Astrocyte Types

Fibrous in white matterProtoplasmic in gray matter

Astrocytes have a unique intermediate filament type, glial fibrillary acidic protein (GFAP).

Astrocytes cont’d

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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

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Glia: Astrocytes

Astrocyte Types

A. Protoplasmic astrocytes and blood vessels (black arrow indicates a microglial cell).B. Fibrous astrocytesC. OligodendrocyteD. Microglia

Myelinating glia

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Glia: MyelinationSchwann cell - myelinating cell of the PNSOligodendrocyte - 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

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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

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Glia: Oligodendrocyte

Electron micrograph

The Schwann cell

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Schwann cell wrapping an axon (red asterisks ). Numerous wraps of the Schwann cell membrane form the myelin

sheath *

Glia: Schwanncell

The node of Ranvier

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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

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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

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Glia: MicrogliaQuiescent vs “activated”

ramified vs ameboid morhpology

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(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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