Among so-called secondary olfactory structures (Haberly, 2001), tdT expression was seen in the dorsal, posterior ventral, lateral, and medial parts of the anterior olfactory nucleus AON (Figures 4J–4L), olfactory tubercles (Figures S4A–S4C), piriform cortex (Figures 4M–4O), anterior cortical amygdala (Figures S4J–S4L), and entorhinal cortex (Figures S4D–S4F). In animals

with more severe symptoms, tdT labeling was observed in tertiary olfactory structures including the insular cortex (Figures 4P–4R), orbital frontal cortex (ORB, Figure S4G–S4I), and hippocampus (HPF, Figures S4M–S4O). To investigate further the anterograde specificity of H129ΔTK-TT, we examined the labeling NLG919 concentration of several classes of neuromodulatory neurons that project directly to the olfactory bulb. We performed this analysis Panobinostat concentration in OMP-Cre mice that exhibited milder symptoms at 6–7 DPI. These mice exhibited tdT expression in the MOE, MOB, piriform cortex (Figures S4P–S4QQ), and olfactory tubercles (data not shown). Despite this multisynaptic anterograde labeling, we did not detect tdT expression in any of the

neuromodulatory populations that project to the MOB, including noradrenergic neurons in the LC (Figures S4R–S4SS, green) (Guevara-Aguilar et al., 1982 and Shipley et al., 1985), cholinergic neurons in the horizontal limb of the diagonal band (HDB) (Figures S4T–S4UU) (Záborszky et al., 1986), or serotonergic neurons in the raphe nuclei (Figures S4V–S4W) (McLean and Shipley, 1987). In mice that showed more advanced symptoms and a wider spread of expression (7–8 DPI), tdT was detected in these neuromodulatory populations (Table S3c). However, this labeling may derive from higher-order olfactory structures known to project to these neuromodulatory centers, including the insular cortex (Peyron et al., 1998), periaqueductal

gray (PAG), medial preoptic area (MPO), medial prefontal cortex, central nucleus of the amygdala not (CEA), and nucleus tractus solitarius (NTS) (Ennis et al., 1998), all of which structures contained tdT+ cells in these mice (Table S3c and Figure S5C). Pheromone-sensing neurons of the vomeronasal organ (VNO) also express OMP and were labeled in OMP-Cre mice infected intranasally with H129ΔTK-TT virus (Figures 5B and 5C). The VNO projects to the accessory olfactory bulb (AOB) through the vomeronasal nerves. The AOB in turn projects to a few areas including the medial amygdala (MeA) and the bed nucleus of the stria terminalis (BST) (Scalia and Winans, 1975 and Yoon et al., 2005), which send further projections to the medial hypothalamic area (Swanson and Petrovich, 1998). We detected tdT expression in the AOB (Figures 5D–5F), MeA (Figures 5G–5I), BST (Figures 5J–5L), and medial preoptic area (MPOA) in the medial hypothalamus (Figures 5M–5O), consistent with labeling of the VNO pathway. In contrast to the relatively limited labeling of brain structures by H129ΔTK-TT in the visual and cerebellar systems, 13.