A nasal chemosensation–dependent critical window for somatosensory development

Abstract

Nasal chemosensation is considered the evolutionarily oldest mammalian sense and, together with somatosensation, is crucial for neonatal well-being before auditory and visual pathways start engaging the brain. Using anatomical and functional approaches in mice, we reveal that odor-driven activity propagates to a large part of the cortex during the first postnatal week and enhances whisker-evoked activation of primary whisker somatosensory cortex (wS1). This effect disappears in adult animals, in line with the loss of excitatory connectivity from olfactory cortex to wS1. By performing neonatal odor deprivation, followed by electrophysiological and behavioral work in adult animals, we identify a key transient regulation of nasal chemosensory information necessary for the development of wS1 sensory-driven dynamics and somatosensation. Our work uncovers a cross-modal critical window for nasal chemosensation–dependent somatosensory functional maturation.

Early-life maturation of the somatosensory cortex: sensory experience and beyond

“…In mouse slice culture between embryonic day (E)18-P12, waves of spontaneous electrical activity initiate in the septum and ventral cortex and propagate dorsally across the cortex, including the somatosensory region ( Conhaim et al, 2011 ). This is consistent with the recent finding that there is direct, transient excitatory connectivity from the olfactory cortex to the somatosensory cortex, and in vivo odor-driven activity propagates broadly across the cortex during the first postnatal week ( Cai et al, 2024 ). This odor-evoked activity enhances whisker-evoked activity in the barrel cortex, while neonatal odor deprivation leads to somatosensory defects in adult mice, suggesting that there is a cross-modal critical window for nasal chemosensation-dependent somatosensory function maturation ( Cai et al, 2024 ).…”

“…This is consistent with the recent finding that there is direct, transient excitatory connectivity from the olfactory cortex to the somatosensory cortex, and in vivo odor-driven activity propagates broadly across the cortex during the first postnatal week ( Cai et al, 2024 ). This odor-evoked activity enhances whisker-evoked activity in the barrel cortex, while neonatal odor deprivation leads to somatosensory defects in adult mice, suggesting that there is a cross-modal critical window for nasal chemosensation-dependent somatosensory function maturation ( Cai et al, 2024 ). Interestingly, recent work quantifying prenatally active neurons in mice using Targeted Recombination in Active Populations (TRAP) identified the piriform cortex as the most abundantly TRAPed region, indicating that early piriform neurons may represent an interconnected hub-like population whose activity promotes recurrent connectivity in the developing cortex ( Wang et al, 2024 ).…”

“…Its precise patterns and timing are essential for many activity-dependent processes during early postnatal development ( Winnubst et al, 2015 ; Wong et al, 2018 ; Duan et al, 2020 ; review: Leighton and Lohmann, 2016 ). Such activity has been suggested to originate from at least four sources: (1) external, passive tactile sensory inputs onto the whiskers from the dam, littermates, and nesting materials ( Akhmetshina et al, 2016 ); (2) sensorimotor feedback generated by involuntary whisker and limb twitches ( Khazipov et al, 2004 ; Tiriac et al, 2014 ; Dooley et al, 2020 ); (3) cross-modal sensory inputs, such as odor-driven activity via direct early excitatory connections from the olfactory cortex to somatosensory cortex ( Henschke et al, 2018 ; Cai et al, 2024 ); 4) internally generated, spontaneous neural activity independent from the periphery or movement ( Moreno-Juan et al, 2017 ; Mizuno et al, 2018 ; Nakazawa et al, 2020 ; Banerjee et al, 2022 ). Multiple lines of evidence support that activity from these different sources co-exist in the first two postnatal weeks.…”

“…There is still considerable ongoing debate over whether the four sources of activity mentioned above are distinct – for example, what proportion of activity that has been attributed as “internally-generated activity” is due to sensorimotor feedback given that the circuitry enabling movement-related sensory feedback is already functional in the thalamus embryonically ( Antón-Bolaños et al, 2019 ; Dooley et al, 2020 ; Blumberg et al, 2022 ). Latest data demonstrating that synchronous activity in the barrel cortex can be driven by chemosensation also raises the possibility that the remaining synchronous activity after inactivation of tactile sensory periphery could have, at least in part, originated from other sensory modalities ( Cai et al, 2024 ; Wang et al, 2024 ). Further investigations will be required to confirm or resolve potential overlaps between sources of early neural activity in the barrel cortex.…”

Neurons for infant social behaviors in the mouse zona incerta

“…Olfaction and tactile sensing by the whiskers are two primary sources of sensory information for developing rodents ( 15 – 19 ). We therefore examined the contribution of olfactory and whisker sensing for the response of ZI SST neurons to interactions with the mother.…”