Neuroscience Research Methods
Viruses?The Optogenetic method is a great example of the user of viruses to help further what we know about the nervous system. Scientists have been able to engineer modified forms of viruses to travel to neurons in the nervous system and implant "on" and "off" switches in the form of rhodopsin receptors on the neuron cell membranes. This allows them to simply shine a specific frequency of light to change the membrane potential of the virus, and therefore, influence neurons' ability to send action potentials to other neurons. If you want to know more about how viruses work to invade our nervous systems (and therefore can be used in neuroscience research!), read this article by Koyuncu, Hogue and Enquist (2013): Virus Infections in the Nervous System.
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How do viruses get into the nervous system?How Do Viruses Get Around in the Nervous System?
Viruses enter neurons in the body three ways: Through Sensory Nerve Endings - Some viruses enter into the nervous system by binding to axon terminal receptors on Peripheral Nervous System (PNS) axons, such as sensory receptors. For example, alpha herpes viruses (such as herpes simplex type-1 (HSV-1), pseudorabies virus (PRV), and bovine herpes virus (BHV) enter the nervous system this way and will stay for a lifetime! They latch on to dynein proteins, which drag them backwards (retrograde) to the soma (See A below). Then they attach themselves to the nucleus of the neuron and wait.... until a stressful event kicks them into gear, hijacking the neuron's RNA and forcing it to regenerate many new copies of the virus... By Invading Motor Neurons at neuromuscular junctions (NMJ) - Viruses can also enter at the synapses between motor neuron axon terminals and muscles called Neuromuscular Junctions (NMJs) (see B. in the figure below). Once they have invaded the axon terminals, they travel backwards (retrograde) through the motor neuron via axoplasmic transport to it's soma located in the spinal cord. These neurons synapse directly to neurons in the Central Nervous System (CNS) via interneurons, and just like that, the virus is on its way to the brain... By Entering the Brain (Almost) Directly Through Neurons in the Nasal Epithelium - Viruses gain speedy contact with the CNS when they are able to penetrate the nose and make contact with the upper nasal cavity. The upper nasal cavity contains the nasal epithelium, which houses tiny smell-sensitive olfactory receptors on dendrites of neurons that synapse directly with the olfactory bulb in the CNS - that means viruses in the nose are literally 1 synapse away from the brain... (see C below). Influenza A virus is thought to travel backwards (retrograde) to the central nervous system like this... In addition, viruses can enter the brain via the "Trojan Horse" Method - by Infecting Leukocytes - viruses can hide within leukocytes (white blood cells that are part of our natural arsenal of immune cells) and hide there until they travel through the Blood Brain Barrier (BBB) (they can pass through the BBB very easily)... Once they are in, they wreak destruction In summary, other than the "Trojan Horse" method, viruses enter neurons through the axon terminals and generally travel backward via axoplasmic transport to the soma of the neuron.... But if Viruses Consistently Travel in a Backwards (Retrograde) Direction, How Can There Be Anterograde (Forward) Travelling Viruses...?WELL... I found this quote in the Koyuncu, Hogue and Enquist (2013) article:
"In contrast to motor neurons, sensory neurons are typically pseudounipolar, with two axon-like projections: one innervating peripheral tissues, and the other making pre-synaptic contact with CNS neurons... To be able to spread within this pseudounipolar architecture, the alpha herpesviruses have evolved the capacity to spread in the anterograde direction, exiting from axon termini. The alpha herpesviruses are among the very few viruses that are capable of bidirectional spread (both anterograde and retrograde direction)" (Koyuncu, Hogue, & Enquist, 2013, para) In other words, some viruses (those that travel via sensory neurons) have HAD to develop the ability to travel in the forward direction from soma to axon terminal, because once they arrive at the soma of a unipolar sensory neuron, the will have to travel again via the axon in order to arrive at the other end of the neuron... |