Abstract
The rodent olfactory bulb (OB) contains two distinct populations of postnatally born interneurons, mainly granule cells (GCs), to support local circuits throughout life. During the early postnatal period (i.e., 2 weeks after birth), GCs are mostly produced locally from progenitor cells in the OB with a proportion of them deriving from proliferating cells in the rostral migratory stream (RMS). Afterward, the replenishment of GCs involves differentiated neuroblasts from the subventricular zone (SVZ) in a process known as adult neurogenesis. Although numerous studies have addressed the role of SVZ-born GCs in olfactory behaviors, the function of GCs produced early postnatally in the OB remains elusive. Our previous study demonstrated that the translational regulator, cytoplasmic polyadenylation element-binding protein 4 (CPEB4), is a survival factor exclusively for neonate-born but not SVZ/adult-derived GCs, so CPEB4-knockout (KO) mice provide unique leverage to study early postnatal-born GC-regulated olfactory functions. CPEB4-KO mice with hypoplastic OBs showed normal olfactory sensitivity and short-term memory, but impaired ability to spontaneously discriminate two odors. Such olfactory dysfunction was recapitulated in specific ablation of Cpeb4 gene in inhibitory interneurons but not in excitatory projection neurons or SVZ-derived interneurons. The continuous supply of GCs from adult neurogenesis eventually restored the OB size but not the discrimination function in 6-month-old KO mice. Hence, in the early postnatal OB, whose function cannot be replaced by adult-born GCs, construct critical circuits for odor discrimination.
Highlights
Sense of smell allows us to distinguish various odors in the environment and to perceive potential pleasure and danger derived from the odorants
Because the continuous replenishment of granule cells (GCs) from subventricular zone (SVZ) neurogenesis eventually restored the bulbar size but not olfactory function in 6-month-old KO mice, we suggest the inhibitory circuits constructed by cytoplasmic polyadenylation element-binding protein 4 (CPEB4)-dependent neonate-born GCs plays an indispensable role in olfactory discrimination
Because of normal odor discrimination in CPEB4-cKONEX mice (Figure 3C), the role of CPEB4 in either projection neurons or excitatory afferent fibers from the piriform cortex to GCs is not required for olfactory discrimination
Summary
Sense of smell allows us to distinguish various odors in the environment and to perceive potential pleasure and danger derived from the odorants. GCs form dendrodendritic synapses with MCs and TCs to confine their excitability (Isaacson and Strowbridge, 1998; Schoppa et al, 1998; Takahashi et al, 2016). This lateral inhibition enhances the contrast between activated glomerular units by gating the tuning specificity of projection neurons before sending an integrated signal to the olfactory cortex (Katoh et al, 1993; Yokoi et al, 1995; Xiong and Chen, 2002)
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