Compositions and methods for monosynaptic transport

A neuron labeling method, comprising:

• contacting one or more primary neurons, each of which is connected to a plurality of secondary neurons by a plurality of synapses, with:
• a neurotropic virus, which is defective for its native glycoprotein and which comprises a foreign glycoprotein from a non-neurotropic virus;
• (ii) at least one nucleic acid molecule that:
• (a) encodes a neuron-specific viral glycoprotein, which glycoprotein is not substantially transported across the plurality of synapses;
• (b) encodes a receptor specific for the foreign glycoprotein;
• and
• (c) is not substantially transported across the plurality of synapses;
• under conditions that permit expression of the neuron-specific viral glycoprotein and the receptor in the primary neuron(s), and retrograde transport of the virus from the primary neuron(s) to the plurality of secondary neurons across the plurality of synapses;
• and
• detecting the virus.

A neuron labeling method, comprising:

• contacting one or more primary neurons, each of which is connected to a plurality of secondary neurons by a plurality of synapses, with:
• (i) a rabies virus defective for its native glycoprotein, which virus comprises:
• (a) a chimeric glycoprotein comprising the cytoplasmic domain of a rabies virus glycoprotein and an extracellular domain and a transmembrane domain of an avian sarcoma and leucosis virus subgroup A (ASLV-A) glycoprotein, and
• (b) a viral genome, comprising a nucleic acid sequence that encodes a detectable polypeptide;
• (ii) at least one nucleic acid molecule that:
• (a) encodes the native viral glycoprotein;
• (b) encodes a receptor specific for the ASLV-A extracellular domain;
• and
• (c) is not substantially transported across the at least one synapse;
• under conditions that permit expression of the native viral glycoprotein, the receptor, and the detectable polypeptide in the primary neuron(s), and retrograde transport of the rabies virus from the primary neuron(s) to the plurality of secondary neurons across the plurality of synapses;
• and
• detecting the detectable protein.

A method for monosynaptic transport of a virus defective for transsynaptic transport (TST-defective virus), comprising contacting one or more primary neurons, each of which is connected by a plurality of synapses to a plurality of secondary neurons, with:

• (i) a TST-defective virus;
• and
• (ii) one or more nucleic acid molecules encoding one or more polypeptides that complement in trans the TST-defective phenotype of the TST-defective virus, and which nucleic acid molecule(s) and polypeptide(s) are not substantially transported across the plurality of synapses;
• under conditions that permit expression of the polypeptide(s) in the primary neuron(s), rescue of the TST-defective phenotype by the polypeptide(s) in the primary neuron, and transport of the TST-defective virus from the primary neuron(s) to the plurality of secondary neurons across the plurality of synapses.