Injury and recovery of neural circuit for behavioral adaptation

Akio Tsuboi (Nara Medical University)

“Functional recovery of neural circuits in the ischemic brain by using newborn neurons”

Sensory experience is recognized as a critical factor in the development and plastic modification of neural circuits in vertebrates. As well as newborn hippocampal neurons, newborn olfactory bulb (OB) interneurons are a good model for studying the postnatal modification of neural circuits by sensory inputs from the external world. Precursors for OB interneurons are generated throughout life in the subventricular zone of the lateral ventricle, migrate along the rostral migratory stream and differentiate into GABA-releasing inhibitory interneurons, such as periglomerular cells and granule cells. It is well known that odor-evoked neural activity affects the survival and integration of newborn OB interneurons. Moreover, odor-deprivation and odor-enriched environments suppress and facilitate, respectively, dendritogenesis and spinogenesis in newborn OB interneurons. However, molecular mechanisms regulating the sensory experience-dependent dendritogenesis and spinogenesis in OB newborn interneurons remain unknown. Recently, we found that the 5T4 oncofetal trophoblast glycoprotein regulates the dendritic arborization of OB GCs in a sensory input-dependent manner (Yoshihara et al., 2012; Takahashi et al., 2016), whereas the neuronal Per/Arnt/Sim domain protein 4 (Npas4) transcription factor controls the sensory input-dependent dendritic spine formation of OB GCs (Yoshihara et al., 2014). In the current project of “Adaptive Circuit Shift”, we will aim at applying newborn OB interneurons to functional recovery of neural circuits in the ischemic brain.

Recent Publications
1. Takahashi H, Ogawa Y, Yoshihara S, Asahina R, Kinoshita M, Kitano T, Kitsuki M, Tatsumi K, Okuda M, Tatsumi K, Wanaka A, Hirai H, Stern PL, Tsuboi A (2016) A subtype of olfactory bulb interneurons is required for odor detection and discrimination behaviors. J Neurosci in press.
2. Yoshihara S, Takahashi H, Nishimura N, Kinoshita M, Asahina R, Kitsuki M, Tatsumi K, Furukawa-Hibi Y, Hirai H, Nagai T, Yamada K, Tsuboi A (2014) Npas4 regulates Mdm2 and thus Dcx in experience-dependent dendritic spine development of newborn olfactory bulb interneurons. Cell Rep 8:843-857.
3. Yoshihara S, Takahashi H, Nishimura N, Naritsuka H, Shirao T, Hirai H, Yoshihara Y, Mori K, Stern PL, Tsuboi A (2012) 5T4 glycoprotein regulates the sensory input-dependent development of a specific subtype of newborn interneurons in the mouse olfactory bulb. J Neurosci 32:2217-2226.