In the olfactory bulb of adult rodents, local interneurons are constantly replaced by immature precursors derived from the subventricular zone. Whether any olfactory sensory process specifically relies on this cell renewal remains largely unclear. By using the well known model of mating-induced imprinting to avoid pregnancy block, which requires accessory olfactory bulb (AOB) function, we demonstrate that this olfactory memory formation critically depends on the presence of newborn granule neurons in this brain region. We show that, in adult female mice, exposure to the male urine compounds involved in mate recognition increases the number of new granule cells surviving in the AOB. This process is modulated by male signals sensed through the vomeronasal organ and, in turn, changes the activity of the downstream amygdaloid and hypothalamic nuclei involved in the pregnancy block response. Chemical depletion of newly generated bulbar interneurons causes strong impairment in mate recognition, thus resulting in a high pregnancy failure rate to familiar mating male odors. Taken together, our results indicate that adult neurogenesis is essential for specific brain functions such as persistent odor learning and mate recognition.

Newborn neurons generated by proliferative progenitors in the adult subventricular zone (SVZ) integrate into the olfactory bulb circuitry of mammals. Survival of these newly-formed cells is regulated by the olfactory input. The presence of new neurons in the accessory olfactory bulb (AOB) has already been demonstrated in some mammalian species, albeit their neurochemical profile and functional integration into AOB circuits are still to be investigated. To unravel whether the mouse AOB represents a site of adult constitutive neurogenesis and whether this process can be modulated by extrinsic factors, we have used multiple in vivo approaches. These included fate mapping of bromodeoxyuridine-labelled cells, lineage tracing of SVZ-derived enhanced green fluorescent protein-positive engrafted cells and neurogenesis quantification in the AOB, in both sexes, as well as in females alone after exposure to male-soiled bedding or its derived volatiles. Here, we show that a subpopulation of SVZ-derived neuroblasts acquires proper neurochemical profiles of mature AOB interneurons. Moreover, 3D reconstruction of long-term survived engrafted neuroblasts in the AOB confirms these cells show features of fully integrated neurons. Finally, exposure to male-soiled bedding, but not to its volatile compounds, significantly increases the number of new neurons in the AOB, but not in the main olfactory bulb of female mice. These data show SVZ-derived neuroblasts differentiate into new functionally integrated neurons in the AOB of young and adult mice. Survival of these cells seems to be regulated by an experience-specific mechanism mediated by pheromones.

The medial subnucleus of the amygdala (MeA) plays a central role in processing sensory cues required for innate behaviors. However, whether there is a link between developmental programs and the emergence of inborn behaviors remains unknown. Our previous studies revealed that the telencephalic preoptic area (POA) embryonic niche is a novel source of MeA destined progenitors. Here, we show that the POA is comprised of distinct progenitor pools complementarily marked by the transcription factors Dbx1 and Foxp2. As determined by molecular and electrophysiological criteria this embryonic parcellation predicts postnatal MeA inhibitory neuronal subtype identity. We further find that Dbx1-derived and Foxp2+ cells in the MeA are differentially activated in response to innate behavioral cues in a sex-specific manner. Thus, developmental transcription factor expression is predictive of MeA neuronal identity and sex-specific neuronal responses, providing a potential developmental logic for how innate behaviors could be processed by different MeA neuronal subtypes.DOI: http://dx.doi.org/10.7554/eLife.21012.001

SUMMARY Because molecular mechanisms underlying refractory focal epilepsy are poorly defined, we performed transcriptome analysis on human epileptogenic tissue. Compared with controls, expression of Circadian Locomotor Output Cycles Kaput (CLOCK) is decreased in epileptogenic tissue. To define the function of CLOCK, we generated and tested the Emx-Cre; Clockflox/flox and PV-Cre; Clockflox/flox mouse lines with targeted deletions of the Clock gene in excitatory and parvalbumin (PV)-expressing inhibitory neurons, respectively. The Emx-Cre; Clockflox/flox mouse line alone has decreased seizure thresholds, but no laminar or dendritic defects in the cortex. However, excitatory neurons from the Emx-Cre; Clockflox/flox mouse have spontaneous epileptiform discharges. Both neurons from Emx-Cre; Clockflox/flox mouse and human epileptogenic tissue exhibit decreased spontaneous inhibitory post-synaptic currents. Finally, video-EEG of Emx-Cre; Clockflox/flox mice reveals epileptiform discharges during sleep and also seizures arising from sleep. Altogether, these data show that disruption of CLOCK alters cortical circuits and may lead to generation of focal epilepsy.