Dynamic Impairment of Olfactory Behavior and Signaling Mediated by an Olfactory Corticofugal System

Abstract

Processing of olfactory information is modulated by centrifugal projections from cortical areas, yet their behavioral relevance and underlying neural mechanisms remain unclear in most cases. The anterior olfactory nucleus (AON) is part of the olfactory cortex, and its extensive connections to multiple upstream and downstream brain centers place it in a prime position to modulate early sensory information in the olfactory system. Here, we show that optogenetic activation of AON neurons in awake male and female mice was not perceived as an odorant equivalent cue. However, AON activation during odorant presentation reliably suppressed behavioral odor responses. This AON-mediated effect was fast and constant across odors and concentrations. Likewise, activation of glutamatergic AON projections to the olfactory bulb (OB) transiently inhibited the excitability of mitral/tufted cells (MTCs) that relay olfactory input to the cortex. Single-unit MTC recordings revealed that optogenetic activation of glutamatergic AON terminals in the OB transiently decreased sensory-evoked MTC spiking, regardless of the strength or polarity of the sensory response. The reduction in MTC firing during optogenetic stimulation was confirmed in recordings in awake mice. These findings suggest that glutamatergic AON projections to the OB impede early olfactory signaling by inhibiting OB output neurons, thereby dynamically gating sensory throughput to the cortex.

Genetic influences of autism candidate genes on circuit wiring and olfactory decoding

“…The abundant top-down influence from olfactory cortices to the MOB mainly targets the granule cells (for a review of the MOS, see Brann and Datta 2020;Schäfer et al this issue). Top-down influence on MOB by the AON and the anterior piriform cortex has been described previously (Boyd et al 2012(Boyd et al , 2015Markopoulos et al 2012;Rothermel and Wachowiak 2014;Oettl et al 2016;Quintela et al 2020 and reviewed by Rothermel et al this issue).…”

Extrinsic neuromodulation in the rodent olfactory bulb

“…AONpP sends, similar to PC, sensory-evoked feedback to the OB (Rothermel and Wachowiak 2014 ) but only a few studies have investigated the influence of centrifugal AONpP projections on in vivo OB circuit function. Activation of AONpP derived fibers strongly inhibits sensory signaling of olfactory output neurons both in the anesthetized (Markopoulos et al 2012 ; Medinaceli Quintela et al 2020 ) as well as in the awake behaving mouse (Medinaceli Quintela et al 2020 ) suggesting a type of gating function. In contrast to that, AONpE corticofugal projections seem to be exclusively contralateral (Schoenfeld and Macrides 1984 ; Yan et al 2008 ).…”

Chronic chemogenetic stimulation of the anterior olfactory nucleus reduces newborn neuron survival in the adult mouse olfactory bulb

“…These existing granule cells in their turn inhibit mitral cells, thought to increase the discriminatory potential of the OB network. The paradigm of our continuous stimulation might have caused a long-term inhibition of the OB network, blocked all sensory input, and therefore mimicked sensory deprivation as occurred through optogenetic activation of the AON in a very recent study (Medinaceli Quintela et al, 2020).…”

“…This leaves us to the discussion, why AON activation would lead to a decrease in newborn neurons. Multiple studies have demonstrated that the AON can regulate the inhibitory network in the OB by activation of granule cells (Markopoulos et al, 2012;Medinaceli Quintela et al, 2020;Oettl et al, 2016). These existing granule cells in their turn inhibit mitral cells, thought to increase the discriminatory potential of the OB network.…”