Recurrent cortical circuits implement concentration-invariant odor coding

Abstract

Although the ability to reliably identify objects over a large range of stimulus intensities is a fundamental feature of all sensory systems, the neural circuit mechanisms that implement intensity invariance remain poorly understood. In mammals, odors are detected by individual olfactory sensory neurons expressing just one out of ~1,000 different types of odorant receptor, each of which projects to a specific pair of glomeruli in the olfactory bulb (OB). At low concentrations, odorants selectively bind high-affinity receptors, activating a sparse combination of responsive glomeruli. However, receptor activation, and thus glomerular activation, becomes less specific at higher odorant concentrations (1-4), potentially degrading the representation of odor identity. However, psychophysical studies indicate that odors retain their perceptual identities while concentration varies over several orders of magnitude (5-7). The olfactory system must therefore transform these concentration-dependent odor responses at early stages of processing into concentration-invariant representations of odor identity.Animals rely on olfaction to find food, attract mates and avoid predators. To support these behaviors, animals must reliably identify odors across different odorant concentrations. The neural circuit operations that implement this concentration invariance remain unclear. Here we demonstrate that, despite concentration-dependence in olfactory bulb (OB), representations of odor identity are preserved downstream, in piriform cortex (PCx). The OB cells responding earliest after inhalation drive robust responses in a sparse subset of PCx neurons. Recurrent collateral connections broadcast their activation across PCx, recruiting strong, global feedback inhibition that rapidly suppresses cortical activity for the remainder of the sniff, thereby discounting the impact of slower, concentration-dependent OB inputs. Eliminating recurrent collateral output dramatically amplifies PCx odor responses, renders cortex steeply concentration-dependent, and abolishes concentration-invariant identity decoding.

Representational drift in primary olfactory cortex

“…Representations of the external world in sensory cortices may define the identity of a stimulus and should therefore vary little over the life of the organism. In the olfactory system the primary olfactory cortex, piriform, is thought to determine odor identity [1][2][3][4][5][6] . We have performed electrophysiological recordings of single units maintained over weeks to examine the stability of odor representations in the mouse piriform cortex.…”

Complex neural representation of odour information in the olfactory bulb

“…Piriform cortex is the most important cortical region for olfaction and projects directly to the OB. It has the ability to encode information about the identity, intensity and timing of odours . More importantly, piriform cortex plays a major role in odour preference learning, odour pattern separation, olfactory learning, odour fear memory and the processing of odour objects .…”

Mixture coding and segmentation in the anterior piriform cortex

“…These include interactions between odorants at the olfactory epithelium (Kurahashi et al, 1994;Duchamp-Viret et al, 2003;Oka et al, 2004;Grossman et al, 2008;Takeuchi et al, 2009;Reddy et al, 2018;Xu et al, 2019;Zak et al, 2019), processing in the olfactory bulb (Giraudet et al, 2002;Linster and Cleland, 2004;Tabor et al, 2004;Lin et al, 2006), and further normalization within piriform cortex, implemented by local inhibition. Inhibitory circuits within the piriform cortex have indeed been shown to play a major role in shaping piriform representations Isaacson, 2009, 2011;Franks et al, 2011;Bolding and Franks, 2018).…”

“…Sublinearlity of mixture responses is probably inherited to some extent from the olfactory epithelium (Kurahashi et al, 1994;Duchamp-Viret et al, 2003;Oka et al, 2004;Takeuchi et al, 2009;Xu et al, 2020;Zak et al, 2020), as well as from the olfactory bulb where cross odorant inhibition may contribute (Yokoi et al, 1995;Urban, 2002;Aungst et al, 2003;McGann et al, 2005;Arevian et al, 2008;Fantana et al, 2008). The piriform cortex integrates these non-linear odor representations from the olfactory bulb and utilizes local recurrent circuitry to generate representations that presumably support segmentation Isaacson, 2009, 2011;Franks et al, 2011;Miura et al, 2012;Suzuki and Bekkers, 2012;Roland et al, 2017;Bolding and Franks, 2018). Importantly, piriform cortex is also expected to contribute to sublinear summation of mixture components due to local inhibitory circuits.…”

“…Importantly, piriform cortex is also expected to contribute to sublinear summation of mixture components due to local inhibitory circuits. These circuits have been shown to normalize responses to increasing concentrations of odors (Bolding and Franks, 2018;Stern et al, 2018). Whether increasing stimulus intensity by increasing concentration or by adding more odorants produces equivalent normalization is unknown.…”