Brief sensory deprivation triggers cell type-specific structural and functional plasticity in olfactory bulb neurons

Abstract

Can alterations in experience trigger different plastic modifications in neuronal structure and function, and if so, how do they integrate at the cellular level? To address this question, we interrogated circuitry in the mouse olfactory bulb responsible for the earliest steps in odour processing. We induced experience-dependent plasticity in mice by blocking one nostril for a day, a minimally-invasive manipulation which leaves the sensory organ undamaged and is akin to the natural transient blockage suffered during common mild rhinal infections. We found that such brief sensory deprivation produced structural and functional plasticity in one highly specialised bulbar cell type: axon-bearing dopaminergic neurons in the glomerular layer. After 24h naris occlusion, the axon initial segment (AIS) in bulbar dopaminergic neurons became significantly shorter, a structural modification that was also associated with a decrease in intrinsic excitability. These effects were specific to the AIS-positive dopaminergic subpopulation, because no experience-dependent alterations in intrinsic excitability were observed in AIS-negative dopaminergic cells. Moreover, 24h naris occlusion produced no structural changes at the AIS of bulbar excitatory neuronsmitral/tufted and external tufted cells -nor did it alter their intrinsic excitability. By targeting excitability in one specialised dopaminergic subpopulation, experience-dependent plasticity in early olfactory networks might act to fine-tune sensory processing in the face of continually fluctuating inputs.

Brief sensory deprivation triggers plasticity of dopamine-synthesising enzyme expression in genetically labelled olfactory bulb dopaminergic neurons

“…Having shown that the DAT-tdTomato mouse line labels olfactory bulb neurons that are predominantly dopaminergic but include a distinct subset of calretinin-positive cells, we went on to use this line for naturally-relevant manipulations of sensory experience (Fokkens et al ., 2012; Galliano et al, 2021). In juvenile mice from postnatal day (P)27, we induced brief 1- or 3-day periods of sensory deprivation without damaging the olfactory epithelium, via unilateral naris occlusion with a plastic plug (Fig.2A; Cummings et al ., 1997; Kikuta et al ., 2015; Cheetham et al ., 2016; Galliano et al, 2021).…”

“…Our data showing decreased TH expression after olfactory sensory deprivation are entirely consistent with a large body of prior work describing this effect (Nadi et al ., 1981; Baker et al ., 1983, 1984, 1993, 1999; Kosaka et al ., 1987; Baker, 1990; Stone et al ., 1990; Cho et al ., 1996; Philpot et al ., 1998; Saino-Saito et al ., 2004; Bastien-Dionne et al ., 2010; Cave et al ., 2010; Weiss et al ., 2011; Grier et al ., 2016), including some indications that it can occur after relatively brief manipulations (Cho et al ., 1996; Akiba et al ., 2007; Chand et al ., 2015; Galliano et al, 2021). It is novel, however, that our methodological approach demonstrated activity-dependent TH alterations in cells identified in an entirely TH-independent manner.…”

“…In juvenile mice from postnatal day (P)27, we induced brief 1-or 3-day periods of sensory deprivation without damaging the olfactory epithelium, via unilateral naris occlusion with a plastic plug (Fig. 2A; Cummings et al, 1997;Kikuta et al, 2015;Cheetham et al, 2016;Galliano et al, 2021). Because of interpretational issues caused by abnormal airflow through the contralateral naris in such manipulations (Coppola, 2012;Kass et al, 2013), we did not compare deprived versus spared olfactory bulbs in the same animals, and instead made all comparisons between the right bulbs of individual occluded or control mice (see Methods).…”

Pathological consequences of chronic olfactory inflammation on neurite morphology of olfactory bulb projection neurons

“…One of the most essential components of the AIS is the cytoskeletal-associated protein, Ankyrin-G (AnkG) 40 . Previous studies have shown that shorter or fewer AISes measured by AnkG are indicative of impairments to the neurons physiology, such as a decrease in excitability 39,41,42 . We first co-stained OB sections with AnkG and Tbx21, an OB projection neuron-specific marker, and confirmed that the vast majority of AnkG+ AISes present in the EPL and MCL are derived from TCs and MCs, respectively (Supplementary Fig.…”

“…To examine the alterations in cellular activity of the OB projection neuros, we stained OBs with an antibody against phoso-S6 ribosomal protein (pS6), one of neuronal activity markers 43 . A recent study demonstrated that pS6 is an exceptional activity marker for OB projection neurons, and that naris occlusion is capable of significantly reducing the expression of pS6 among projection neurons on the ipsilateral OB 41 . It is also worth noting that the vast majority of pS6expressing projection neuron somata were double-positive for Tbx21 (Supplementary Fig.…”