Neuroanatomical Mapping And Stress-related Neural Circuits Of The Tree Shrew Brain

The day-active tree shrew (Tupaia belangeri), a representative of the order Scandentia, is the closest relative of primates. The tree shrew represents a species of choice given day-active animal, small size, ease of handling and feeding, a relatively short gestation period and puberty, and ethical considerations. Recently, there are many attempts to use tree shrews as animal models for human diseases. In the present study, we focus on neuroanatomy and stress-related behaviors in Chinese tree shrews.The main findings are as follows.1. The Tree shrew brain in stereotaxic coordinatesWe provided entirely series of coronal sections, sagittal sections, and horizontal sections using Nissl staining or acetylcholinesterase histochemistry. The coronal sections are presented at0.12mm intervals, which is sufficient to represent all major structures in the tree shrew brain for modern neuroscience research purposes. Further, we showed series of the diagrams as well as the microphotographs of the Nissl-and AChE-stained microphotographs at single-cell resolution. In addition, we also presented MR images acquired with a9.4T MR scanner.2. Distribution of vasopressin (VP), oxytocin (OXT), vasoactive intestinal polypeptide (VIP) and neuropeptide Y (NPY) in the tree shrew brain.Most of VP and OXT immunoreactive (-ir) neurons were found in the paraventricular nucleus and supraoptic nucleus of the tree shrew hypothalamus. Interestingly, a high density of VP-ir fibers within the ventral lateral septum was observed in males but not in females. Both VP-ir and VIP-ir neurons were found in different subdivisions of the suprachiasmatic nucleus with partial overlap. Compared to rats, the tree shrews exhibited a particularly robust and widespread distribution of NPY-ir cells in the main olfactory bulb, bed nucleus of the stria terminalis and amygdala as well as the ventral lateral geniculate nucleus and pretectal nucleus of the thalamus. By contrast, a low density of neurons were scattered in the striatum, neocortex, polymorph cell layer of the dentate gyrus, superior colliculus, inferior colliculus and dorsal tegmental nucleus. These findings provide the first detailed mapping of VP, OXT, VIP and NPY immunoreactivity in the tree shrew brain and demonstrate species differences in the distribution of this neuropeptide.3. Stress-related neural circuits in the tree shrew brainWe found a large number of bed nucleus of the stria terminalis (BST)-projecting neurons in the tree shrew brain. Most of the BST-projecting neurons were found in the tree shrew forebrain. Restaint stress increased c-fos expression in the BST, infralimbic cortex, medial orbital cortex (MO), lateral septal nucleus (LS), supraoptic nucleus, paraventricular hypothalamic nucleus (PVN), lateral hypothalamic area, ventromedial hypothalamic nucleus (VMH), and medial amygdaloid nucleus (MeA). Footshock stress increased c-fos expression in the posterior BST, MO, LS, anterior PVN, VMH, arcuate hypothalamic nucleus, MeA, and periamygdaloid cortex. These findings indicates that neural circuitry of restraint stress is different from that of footshock.4. Social avoidance and anxiety-like behaviors induced by social defeat stress in adult male tree shrewsSubordinate (SUB) and dominant (DOM) subgroups were identified after social defeat stress in adult male tree shrews. Social stress for2months induced significant reduction of social interaction time of SUB. SUB showed significant reduction in distance moved following social-defeat stress. There is a significant difference in social interaction ratio (time spent in the interaction zone in the presence of a social target/time spent in interaction zone without a social target) between SUB and DOM. In the novelty-suppressed feeding, social stress significantly increased the feeding latency of SUB. In addition, there is a significant difference in mean distance from the center point of SUB and DOM to center point of food zone. However, there is no significant difference in sucrose preference and cortisol levels in plasma between SUB and DOM. These results indicate that social defeat stress induces social avoidance and anxiety-like behaviors in subordinate tree shrews.In conclusion, we firstly draw a fine stereotaxic coordinates and immunohistochemical mapping of the neuropeptides in the tree shrew, which supports its close affinity to primates. These stereotaxic coordinates are confirmed by tracer injection in the BST. The neural circuits of stress are different in two aversive stimuli. Finally, we investigate social defeat stress model and stress-related behaviors in tree shrews. These findings provide anatomical basis and stress models for further research.