Postnatal Development of Centrifugal Inputs to the Olfactory Bulb

Abstract

Processing in primary sensory areas is influenced by centrifugal inputs from higher brain areas, providing information about behavioral state, attention, or context. Activity in the olfactory bulb (OB), the first central processing stage of olfactory information, is dynamically modulated by direct projections from a variety of areas in adult mice. Despite the early onset of olfactory sensation compared to other senses, the development of centrifugal inputs to the OB remains largely unknown. Using retrograde tracing across development, we show that centrifugal projections to the OB are established during the postnatal period in an area-specific manner. While feedback projections from the piriform cortex (PIR) are already present shortly after birth, they strongly increase in number during postnatal development with an anterior-posterior gradient. Contralateral projections from the anterior olfactory nucleus (AON) are present at birth but only appeared postnatally for the nucleus of the lateral olfactory tract (nLOT). Numbers of OB projecting neurons from the lateral entorhinal cortex (LEC), ventral hippocampus, and cortical amygdala (CoA) show a sudden increase at the beginning of the second postnatal week and a delayed development compared to more anterior areas. These anatomical data suggest that limited top-down influence on odor processing in the OB may be present at birth, but strongly increases during postnatal development and is only fully established later in life.

Olfactory‐driven beta band entrainment of limbic circuitry during neonatal development

“…However, recent experimental evidence supports their contribution to the here‐described beta band coupling. Morphological assessment showed that centrifugal projections from the LEC and HP start to target the OB during the second postnatal week (Kostka & Bitzenhofer, 2022). They might account for the proportion of unit pairs with positive cross‐covariance lags during spontaneous activity that we described above.…”

“…Of note, beta and gamma power in the OB was reduced following the silencing of MC terminals in the LEC (beta: med: −0.139, iqr: −0.256 to −0.074, P = 0.020; gamma: med: −0.075, iqr: −0.141 to −0.041, P = 0.027; n animals = 9; Wilcoxon's signed-rank test) (Fig. 8C and D) most likely as a result of reduced centrifugal feedback from the LEC and HP (Kostka & Bitzenhofer, 2022). Thus, the direct axonal projections from MCs to the LEC strongly contribute to the oscillatory entrainment of downstream limbic brain areas, such as the HP.…”

Olfactory-driven beta band entrainment of limbic circuitry during neonatal development

“…Of note, beta and gamma power in OB was reduced following the silencing of MC terminals in LEC (RR: med: -0.002, iqr: -0.099 -0.086, p = 0.820; theta: med: -0.039, iqr: -0.127 -0.034, p = 0.426; beta: med: -0.139, iqr: -0.253 --0.074, p = 0.020; gamma: med: -0.062, iqr: -0.111 --0.020, p = 0.020; n=9; Wilcoxon signed-rank test) (Figs 7C and 7Di), most likely as result of reduced centrifugal feedback from LEC and HP [56].…”

Olfactory bulb activity shapes the development of entorhinal-hippocampal coupling and associated cognitive abilities

“… 59 , 60 , 61 In addition, the reduced OB responsiveness could result from abnormal feedback from downstream areas that target the OB via centrifugal projections and emerge during postnatal development. 62 , 63 …”