Neuronal Cell Types and Their Functional Connections
Viruses are infectious agents that target different tissues of the body with great specificity, including the peripheral and central nervous system. These properties can be put to use in identifying particular populations of neurons in the brain and in tracing their synaptic connections. For instance, pseudorabies virus (PRV) infections are quickly transmitted through peripheral nerves to sensory ganglia and often to the brain. This affinity for neurons and ability to spread across synapses offers a method to map connections between neurons. PRV is an excellent tracer of the brain's hardwiring, with few signs of spread to uninvolved circuits.
(Figure 1) Selective fluorescent labeling of neurons A. The suprachiasmatic nucleus 116 hours after injection of PRV 152 into the vitreous of one eye, showing numerous cells labeled with green fluorescent protein on both sides of the SCN. B. Two structures in the thalamus were labelled, the ventral lateral geniculate nucleus (vLGN) and the IGL, while the dorsal LGN was not labeled
Currently, new tracing viruses are being created by Professor Lynn Enquist that express beta-galactosidase and variants of green fluorescent protein to easily visualize the spread of PRV infection in the mammalian nervous system. One such strain, PRV 152, only infects a few of the visual nuclei that receive inputs from the retina, including the suprachiasmatic nucleus (SCN) and the intergeniculate leaflet (IGL) of the thalamus (see figure). By incubating the infection for different periods of time, the number of synapses crossed by the virus can be varied. By combining cell-specific infections with fluorescent labeling, the connections among neuronal populations can be traced much more efficiently than ever before.
Somewhat surprisingly, physiological tests revealed that infected cells exhibited completely normal function, indicating that one can study the functional properties of a neural circuit containing PRV-labeled cells. Because PRV-infected neurons remain healthy, this virus may also be engineered to deliver additional genes to specific populations of cells within the brain and alter the function of that neural circuit.
Contact:
Lynn Enquist