Abstract
Olfactory dysfunction is an early event in Alzheimer’s disease (AD). However, the mechanism underlying the AD-related changes in the olfactory bulb (OB) remains unknown. Granule cells (GCs) in the OB regulate the activity of mitral cells (MCs) through reciprocal dendrodendritic synapses, which is crucial for olfactory signal processing and odor discrimination. Nevertheless, the relationships between the morphological and functional changes of dendrodendritic synapses, particularly the local field potentials (LFPs) as a consequence of olfactory disorders in patients with AD have not been investigated. Here, we studied the morphological and functional changes induced by dendrodendritic inhibition in GCs onto MCs in the OB of amyloid precursor protein (APP)/PS1 mice and age-matched control mice during aging, particular, we focused on the effects of olfactory disorder in the dendrodendritic synaptic structures and the LFPs. We found that olfactory disorder was associated with increased amyloid-β (Aβ) deposits in the OB of APP/PS1 mice, and those mice also exhibited abnormal changes in the morphology of GCs and MCs, a decreased density of GC dendritic spines and impairments in the synaptic interface of dendrodendritic synapses between GCs and MCs. In addition, the aberrant enhancements in the γ oscillations and firing rates of MCs in the OB of APP/PS1 mice were recorded by multi-electrode arrays (MEAs). The local application of a GABAAR agonist nearly abolished the aberrant increase in γ oscillations in the external plexiform layer (EPL) at advanced stages of AD, whereas a GABAAR antagonist aggravated the γ oscillations. Based on our findings, we concluded that the altered morphologies of the synaptic structures of GCs, the dysfunction of reciprocal dendrodendritic synapses between MCs and GCs, and the abnormal γ oscillations in the EPL might contribute to olfactory dysfunction in AD.
Highlights
Alzheimer’s disease (AD), the most common neurodegenerative disorder, results in severe memory and learning impairments (Wei et al, 2010)
The results showed that Aβ deposition induced morphological and functional changes in the dendrodendritic synapses in the external plexiform layer (EPL), and contribute to a more in-depth illustration of the mechanism of olfactory disorders in AD
Compared with the C57 mice, the 3–4mo (p < 0.05, Figure 1D), 6–7-mo (p < 0.05, Figure 1E) and 9–10-mo (p < 0.05, Figure 1F) amyloid precursor protein (APP)/PS1 mice showed decreases in the numbers of correct olfactory discrimination responses per trial, indicating that the level of olfactory discrimination became increasingly impaired as the animals aged
Summary
Alzheimer’s disease (AD), the most common neurodegenerative disorder, results in severe memory and learning impairments (Wei et al, 2010). In the OB, the excitatory sensory inputs from excitatory sensory neurons to mitral cells (MCs) trigger the release of glutamate from their lateral dendrites onto the dendrites of granule cells (GCs), and this section mediates the transmission of the GABAergic inhibition back to MCs (Isaacson and Strowbridge, 1998; Lepousez and Lledo, 2013). The recurrent and lateral inhibition supported by dendrodendritic reciprocal synapses between the dendrites of MCs’ and GCs’ mediates key roles in sensory processing, such as the gain control and odor selectivity of MC responses, which are crucial for proper odor discrimination (Abraham et al, 2010; Tan et al, 2010).
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
