A genetic approach to trace neural circuits

Abstract

Mammalian nervous system function involves billions of neurons which are interconnected in a multitude of neural circuits. Here we describe a genetic approach to chart neural circuits. By using an olfactoryspecific promoter, we selectively expressed barley lectin in sensory neurons in the olfactory epithelium and vomeronasal organ of transgenic mice. The lectin was transported through the axons of those neurons to the olfactory bulb, transferred to the bulb neurons with which they synapse, and transported through the axons of bulb neurons to the olfactory cortex. The lectin also was retrogradely transported from the bulb to neuromodulatory brain areas. No evidence could be obtained for adverse effects of the lectin on odorant receptor gene expression, sensory axon targeting in the bulb, or the generation or transmission of signals by olfactory sensory neurons. Transneuronal transfer was detected prenatally in the odorsensing pathway, but only postnatally in the pheromonesensing pathway, suggesting that odors, but not pheromones, may be sensed in utero. Our studies demonstrate that a plant lectin can serve as a transneuronal tracer when its expression is genetically targeted to a subset of neurons. This technology can potentially be applied to a variety of vertebrate and invertebrate neural systems and may be particularly valuable for mapping connections formed by small subsets of neurons and for studying the development of connectivity as it occurs in utero.

RETRACTED: Odor maps in the olfactory cortex

“…By using extremely high concentrations of odorants, the density of c-Fos ϩ neurons in a hot spot area (Fig. 5Ca) approached that of pyramidal neurons labeled by a transneuronal tracer expressed in all OE neurons (50) (Fig. 5Cb).…”

Neuropathic and inflammatory pain are modulated by tuberoinfundibular peptide of 39 residues

“…20) into the LC area of VGlut2-Cre mice. Many LC area neurons, including some within the pericoerulear area, contained barley lectin immunoreactivity (BL-ir).…”

“…AAV particles (serotype 8; AAV-FLEX-DTR) were produced as described by Cecchini et al (39). AAV encoding Cre-dependent barley lectin (20) expression was produced similarly. Construct sequences were confirmed by using the National Institute of Neurological Disorders and Stroke intramural sequencing facility.…”

Expression of Nonclassical Class I Major Histocompatibility Genes Defines a Tripartite Organization of the Mouse Vomeronasal System

“…The IRES-BL-ACNF cassette, in which tauGFP of the IRES-tauGFP-ACNF was replaced with barley lectin (Horowitz et al, 1999), was inserted in the PacI site, generating the V2rf2-IRES-BL-ACNF targeting vector. The vectors were linearized and electroporated into E14 embryonic stem (ES) cells as described previously (Mombaerts et al, 1996).…”

“…The V2rf2-IRES-barley lectin strain is henceforth abbreviated as V2rf2-BL. Barley lectin is an axonal marker and has also been used for trans-synaptic labeling (Horowitz et al, 1999;Yoshihara et al, 1999;Zou et al, 2001). In coronal sections of the VNO, scattered VSNs are revealed by immunohistochemistry with an anti-BL antibody (Fig.…”