Anterograde tracing

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In neuroscience, anterograde tracing is a research method that is used to trace axonal projections from their source (the cell body, or soma) to their point of termination (the synapse). A hallmark of anterograde tracing is the labeling of the presynaptic and the postsynaptic neuron(s). The crossing of the synaptic cleft is a vital difference between the anterograde tracers and the dye fillers used for morphological reconstruction. The complementary technique is retrograde tracing , which is used to trace neural connections from their termination to their source (i.e. synapse to cell body). [1] Both the anterograde and retrograde tracing techniques are based on the visualization of the biological process of axonal transport.

Contents

The anterograde and retrograde tracing techniques allow the detailed descriptions of neuronal projections from a single neuron or a defined population of neurons to their various targets throughout the nervous system. [2] These techniques allow the "mapping" of connections between neurons in a particular structure (e.g. the eye) and the target neurons in the brain. Much of what is currently known about connectional neuroanatomy was discovered through the use of the anterograde and retrograde tracing techniques. [1]

Techniques

Several methods exist to trace projections originating from the soma towards their target areas. These techniques initially relied upon the direct physical injection of various visualizable tracer molecules (e.g. green fluorescent protein, lipophylic dyes or radioactively tagged amino acids) into the brain. These molecules are absorbed locally by the soma (cell body) of various neurons and transported to the axon terminals, or they are absorbed by axons and transported to the soma of the neuron. Other tracer molecules allow for the visualization of large networks of axonal projections extending from the neurons exposed to the tracer. [1]

Over the recent years viral vectors have been developed and implemented as anterograde tracers to identify the target regions of projecting neurons. [3] [4]

Alternatively strategies are transsynaptic anterograde tracers, which can cross the synaptic cleft, labeling multiple neurons within a pathway. Those can also be genetic or molecular tracers.[ citation needed ]

Recently manganese-enhanced magnetic resonance imaging (MEMRI) has been used to trace functional circuits in living brains, as pioneered by Russ Jacobs, [5] Robia Paultler, [6] Alan Koretsky and Elaine Bearer. [7] The Mn2+ ion gives a hyperintense signal in T1-weighted MRI and thus serves as a contrast agent. Mn2+ enters through voltage dependent calcium channels, is taken into intracellular organelles and is transported by the endogenous neuronal transport system including kinesin-1, accumulating at distant locations. [8] Statistical parametric mapping of Mn accumulation in time-lapse images provides detailed information not only about neuronal circuitry but also about the dynamics of transport within them, and the location of distal connections. [9] This approach provides information about circuitry throughout the brain in living animals.

Genetic tracers

(see also Viral neuronal tracing)

In order to trace projections from a specific region or cell, a genetic construct, virus or protein can be locally injected, after which it is allowed to be transported anterogradely. Viral tracers can cross the synapse, and can be used to trace connectivity between brain regions across many synapses. Examples of viruses used for anterograde tracing are described by Kuypers. [10] Most well known are the herpes simplex virus type1 (HSV) and the rhabdoviruses. [10] HSV was used to trace the connections between the brain and the stomach, in order to examine the brain areas involved in viscero-sensory processing. [11] Another study used HSV type1 and type2 to investigate the optical pathway: by injecting the virus into the eye, the pathway from the retina into the brain was visualized. [12]

Viral tracers use a receptor on the host cell to attach to it and are then endocytosed. For example, HSV uses the nectin receptor and is then endocytosed. After endocytosis, the low pH inside the vesicle strips the envelope of the virion after which the virus is ready to be transported to the cell body. It was shown that pH and endocytosis are crucial for the HSV to infect a cell. [13] Transport of the viral particles along the axon was shown to depend on the microtubular cytoskeleton. [14]

Molecular tracers

There is also a group of tracers that consist of protein products that can be taken up by the cell and transported across the synapse into the next cell. Wheat-germ agglutinin (WGA) and Phaseolus vulgaris leucoagglutinin [15] are the most well known tracers, however they are not strict anterograde tracers: especially WGA is known to be transported anterogradely as well as retrogradely. [16] WGA enters the cell by binding to oligosaccharides, and is then taken up via endocytosis via a caveolae-dependent pathway. [17] [18]

Other anterograde tracers widely used in neuroanatomy are the biotinylated dextran amines (BDA), also used in retrograde tracing.[ citation needed ]

Partial list of studies using this technique

The anterograde tracing technique is now a widespread research technique. The following are a partial list of studies that have used anterograde tracing techniques:

See also

Related Research Articles

<span class="mw-page-title-main">Axon</span> Long projection on a neuron that conducts signals to other neurons

An axon or nerve fiber is a long, slender projection of a nerve cell, or neuron, in vertebrates, that typically conducts electrical impulses known as action potentials away from the nerve cell body. The function of the axon is to transmit information to different neurons, muscles, and glands. In certain sensory neurons, such as those for touch and warmth, the axons are called afferent nerve fibers and the electrical impulse travels along these from the periphery to the cell body and from the cell body to the spinal cord along another branch of the same axon. Axon dysfunction can be the cause of many inherited and acquired neurological disorders that affect both the peripheral and central neurons. Nerve fibers are classed into three types – group A nerve fibers, group B nerve fibers, and group C nerve fibers. Groups A and B are myelinated, and group C are unmyelinated. These groups include both sensory fibers and motor fibers. Another classification groups only the sensory fibers as Type I, Type II, Type III, and Type IV.

<span class="mw-page-title-main">Dendrite</span> Small projection on a neuron that receives signals

A dendrite or dendron is a branched protoplasmic extension of a nerve cell that propagates the electrochemical stimulation received from other neural cells to the cell body, or soma, of the neuron from which the dendrites project. Electrical stimulation is transmitted onto dendrites by upstream neurons via synapses which are located at various points throughout the dendritic tree.

<span class="mw-page-title-main">Neuron</span> Electrically excitable cell found in the nervous system of animals

Within a nervous system, a neuron, neurone, or nerve cell is an electrically excitable cell that fires electric signals called action potentials across a neural network. Neurons communicate with other cells via synapses, which are specialized connections that commonly use minute amounts of chemical neurotransmitters to pass the electric signal from the presynaptic neuron to the target cell through the synaptic gap.

The development of the nervous system, or neural development (neurodevelopment), refers to the processes that generate, shape, and reshape the nervous system of animals, from the earliest stages of embryonic development to adulthood. The field of neural development draws on both neuroscience and developmental biology to describe and provide insight into the cellular and molecular mechanisms by which complex nervous systems develop, from nematodes and fruit flies to mammals.

<span class="mw-page-title-main">Neuroanatomy</span> Branch of neuroscience

Neuroanatomy is the study of the structure and organization of the nervous system. In contrast to animals with radial symmetry, whose nervous system consists of a distributed network of cells, animals with bilateral symmetry have segregated, defined nervous systems. Their neuroanatomy is therefore better understood. In vertebrates, the nervous system is segregated into the internal structure of the brain and spinal cord and the series of nerves that connect the CNS to the rest of the body. Breaking down and identifying specific parts of the nervous system has been crucial for figuring out how it operates. For example, much of what neuroscientists have learned comes from observing how damage or "lesions" to specific brain areas affects behavior or other neural functions.

A histochemical tracer is a compound used to reveal the location of cells and track neuronal projections. A neuronal tracer may be retrograde, anterograde, or work in both directions. A retrograde tracer is taken up in the terminal of the neuron and transported to the cell body, whereas an anterograde tracer moves away from the cell body of the neuron.

Axoplasm is the cytoplasm within the axon of a neuron. For some neuronal types this can be more than 99% of the total cytoplasm.

Synaptogenesis is the formation of synapses between neurons in the nervous system. Although it occurs throughout a healthy person's lifespan, an explosion of synapse formation occurs during early brain development, known as exuberant synaptogenesis. Synaptogenesis is particularly important during an individual's critical period, during which there is a certain degree of synaptic pruning due to competition for neural growth factors by neurons and synapses. Processes that are not used, or inhibited during their critical period will fail to develop normally later on in life.

<span class="mw-page-title-main">Retrograde signaling</span> In biology, a signal traveling backwards to its source

Retrograde signaling in biology is the process where a signal travels backwards from a target source to its original source. For example, the nucleus of a cell is the original source for creating signaling proteins. During retrograde signaling, instead of signals leaving the nucleus, they are sent to the nucleus. In cell biology, this type of signaling typically occurs between the mitochondria or chloroplast and the nucleus. Signaling molecules from the mitochondria or chloroplast act on the nucleus to affect nuclear gene expression. In this regard, the chloroplast or mitochondria act as a sensor for internal external stimuli which activate a signaling pathway.

<span class="mw-page-title-main">Axonal transport</span> Movement of organelles

Axonal transport, also called axoplasmic transport or axoplasmic flow, is a cellular process responsible for movement of mitochondria, lipids, synaptic vesicles, proteins, and other organelles to and from a neuron's cell body, through the cytoplasm of its axon called the axoplasm. Since some axons are on the order of meters long, neurons cannot rely on diffusion to carry products of the nucleus and organelles to the ends of their axons. Axonal transport is also responsible for moving molecules destined for degradation from the axon back to the cell body, where they are broken down by lysosomes.

A neurite or neuronal process refers to any projection from the cell body of a neuron. This projection can be either an axon or a dendrite. The term is frequently used when speaking of immature or developing neurons, especially of cells in culture, because it can be difficult to tell axons from dendrites before differentiation is complete.

<span class="mw-page-title-main">Connectome</span> Comprehensive map of neural connections in the brain

A connectome is a comprehensive map of neural connections in the brain, and may be thought of as its "wiring diagram". An organism's nervous system is made up of neurons which communicate through synapses. A connectome is constructed by tracing the neuron in a nervous system and mapping where neurons are connected through synapses.

<span class="mw-page-title-main">Chromatolysis</span> Dissolution of a neurons Nissl bodies

In cellular neuroscience, chromatolysis is the dissolution of the Nissl bodies in the cell body of a neuron. It is an induced response of the cell usually triggered by axotomy, ischemia, toxicity to the cell, cell exhaustion, virus infections, and hibernation in lower vertebrates. Neuronal recovery through regeneration can occur after chromatolysis, but most often it is a precursor of apoptosis. The event of chromatolysis is also characterized by a prominent migration of the nucleus towards the periphery of the cell and an increase in the size of the nucleolus, nucleus, and cell body. The term "chromatolysis" was initially used in the 1940s to describe the observed form of cell death characterized by the gradual disintegration of nuclear components; a process which is now called apoptosis. Chromatolysis is still used as a term to distinguish the particular apoptotic process in the neuronal cells, where Nissl substance disintegrates.

<span class="mw-page-title-main">Retrograde tracing</span> Technique for mapping neural circuits in the "upstream" direction, from target to source

Retrograde tracing is a research method used in neuroscience to trace neural connections from their point of termination to their source. Retrograde tracing techniques allow for detailed assessment of neuronal connections between a target population of neurons and their inputs throughout the nervous system. These techniques allow the "mapping" of connections between neurons in a particular structure and the target neurons in the brain. The opposite technique is anterograde tracing, which is used to trace neural connections from their source to their point of termination. Both the anterograde and retrograde tracing techniques are based on the visualization of axonal transport.

Viral neuronal tracing is the use of a virus to trace neural pathways, providing a self-replicating tracer. Viruses have the advantage of self-replication over molecular tracers but can also spread too quickly and cause degradation of neural tissue. Viruses that can infect the nervous system, called neurotropic viruses, spread through spatially close assemblies of neurons through synapses, allowing for their use in studying functionally connected neural networks.

Neuronal tracing, or neuron reconstruction is a technique used in neuroscience to determine the pathway of the neurites or neuronal processes, the axons and dendrites, of a neuron. From a sample preparation point of view, it may refer to some of the following as well as other genetic neuron labeling techniques,

<span class="mw-page-title-main">Pre-locus coeruleus</span>

Pre-locus coeruleus is a small nucleus in the brainstem. This small cluster of neurons also is referred to by the abbreviation "pre-LC". It was named "pre-LC" because it lies just rostral to the locus coeruleus, which is commonly abbreviated "LC".

<span class="mw-page-title-main">Tripartite synapse</span>

Tripartite synapse refers to the functional integration and physical proximity of:

<span class="mw-page-title-main">Neurotubule</span>

Neurotubules are microtubules found in neurons in nervous tissues. Along with neurofilaments and microfilaments, they form the cytoskeleton of neurons. Neurotubules are undivided hollow cylinders that are made up of tubulin protein polymers and arrays parallel to the plasma membrane in neurons. Neurotubules have an outer diameter of about 23 nm and an inner diameter, also known as the central core, of about 12 nm. The wall of the neurotubules is about 5 nm in width. There is a non-opaque clear zone surrounding the neurotubule and it is about 40 nm in diameter. Like microtubules, neurotubules are greatly dynamic and the length of them can be adjusted by polymerization and depolymerization of tubulin.

<span class="mw-page-title-main">Campenot chamber</span>

A Campenot chamber is a three-chamber petri dish culture system devised by Robert Campenot to study neurons. Commonly used in neurobiology, the neuron soma or cell body is physically compartmentalized from its axons allowing for spatial segregation during investigation. This separation, typically done with a fluid impermeable barrier, can be used to study nerve growth factors (NGF). Neurons are particularly sensitive to environmental cues such as temperature, pH, and oxygen concentration which can affect their behavior.

References

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