An intrinsic vasopressin system in the olfactory bulb is involved in social recognition

Abstract

Many peptides, when released as chemical messengers within the brain, have powerful influences on complex behaviours. Most strikingly, vasopressin and oxytocin, once thought of as circulating hormones whose actions were confined to peripheral organs, are now known to be released in the brain, where they have fundamentally important roles in social behaviours. In humans, disruptions of these peptide systems have been linked to several neurobehavioural disorders, including Prader-Willi syndrome, affective disorders and obsessive-compulsive disorder, and polymorphisms of V1a vasopressin receptor have been linked to autism. Here we report that the rat olfactory bulb contains a large population of interneurons which express vasopressin, that blocking the actions of vasopressin in the olfactory bulb impairs the social recognition abilities of rats and that vasopressin agonists and antagonists can modulate the processing of information by olfactory bulb neurons. The findings indicate that social information is processed in part by a vasopressin system intrinsic to the olfactory system.

Figure 1. Vasopressin neurons in the olfactory bulb

a, Most vasopressin cells in eGFP transgenic rats (DAB staining) are in the periglomerular region throughout the main olfactory bulb. b, An apical dendrite ramifies into a glomerulus (blue staining, periglumerular cell marker calbindin 28K). Confirmation using antibodies against (c) GFP and (d) vasopressin in transgenic rats and (e) vasopressin in wild-type rats. f, in situ hybridisation for vasopressin mRNA. g-i, Vasopressin cells do not co-express calbindin, calretinin or GABA (red), but (j-l) contain glutamate. m-o, FluoroGold labelling after injection into the anterior olfactory nucleus in mitral and periglomerular cells, but not vasopressin cells. V1a receptors are expressed on (p) mitral cells and many periglomerular neurones, but not on (q) vasopressin cells, whereas some vasopressin cells express V1b receptors (r). s, Patch-clamp recording indicate firing patterns (spontaneous and depolarized) like those of ET cells. GCL granule cell layer, MCL mitral cell layer, EPL epiform plexus layer, GL glomerular layer. Scale bars 20μm.

Figure 2. Effects of V1a receptor blockade and vasopressin cell destruction on social recognition

a, A juvenile (J) is presented to an adult male (A) for 4min. This juvenile is removed and after 30 or 180min is re-presented together with a non-familiar juvenile, and the preference index calculated. b, administration of V1 antagonist results in performance similar to that after extinction of short-term discrimination (after 180min). c, V1a receptor siRNA similarly impairs discrimination after 4, 8 and 16 days of treatment. d, Selective destruction of vasopressin cells via diphtheria toxin injection results in a similar impairment of discrimination in transgenic rats, but not in wild-type rats. Means+S.E.M., * P<0.05 and ** P<0.001 vs control; numbers in columns are n/group.

Figure 3. Specificity of effects on social recognition

a, Control rats and siRNA-treated rats showed similar habituation and dishabituation to volatile scents. b, Control rats also showed habituation and dishabituation to juveniles, siRNA-treated rats showed neither. c, Neither siRNA nor diphtheria toxin injection affected object recognition (c). Means+S.E.M., * P<0.05 vs trial 4 and same treatment; numbers in columns are n/group.

Figure 4. Vasopressin effects on mitral cells

Effects of (a) vasopressin and (b) V1 antagonist on firing rate (a) and instantaneous frequency in a single, representative mitral cell (a,b). The inset in a shows raw waveform traces of spike activity. c, Vasopressin reduced the activity quotient in 6 cells treated with 4ng and 7 treated with 40ng vasopressin, and increased it in 7 cells treated with antagonist (d) the hazard function overlay shows the reduction in doublet firing in a typical cell (light line before, heavy line after vasopressin) (e) change in number of doublets (intervals<10ms); quantified for all doublet cells f, top; spike activity in a mitral cell, showing activity modulated by respiratory rhythm 5s before and after odour; below, cumulative spikes from four tests during bursts before (above) and after (below) vasopressin. g, number of spikes 5s before and 5s after odour for the tests in (f). h, responses of another cell to odour (arrows) before, during and after aCSF and vasopressin. i, expanded instantaneous frequency records of the cell shown in (h). j, Mean odour response in 16 cells tested with vasopressin, 7 of which were also tested with aCSF, and in 10 of which recordings were maintained long enough to observe recovery. Means+S.E.M. *P<0.05.