Research Article

Recurrent cortical circuits implement concentration-invariant odor coding

See allHide authors and affiliations

Science  14 Sep 2018:
Vol. 361, Issue 6407, eaat6904
DOI: 10.1126/science.aat6904

You are currently viewing the abstract.

View Full Text

Log in to view the full text

Log in through your institution

Log in through your institution

Representing the identity of a smell

We still don't know how odors retain their identities over a range of concentrations. Working in mice, Bolding and Franks simultaneously recorded spiking activity from neurons in the olfactory bulb and piriform cortex, two important brain regions for olfaction. Odor information was transformed from a representation that was highly concentration dependent in the olfactory bulb to a representation that was largely concentration invariant in the piriform cortex. The underlying mechanism involves a “winner-takes-all” lateral inhibition. In the collateral network of the piriform cortex, the principal cells responded promptly to output from the olfactory bulb, and recurrent inhibition curtailed the intensity dependence of the signal.

Science, this issue p. eaat6904

Structured Abstract

INTRODUCTION

Objects can appear remarkably stable despite the often fickle cues they provide to our senses. For instance, a foraging mouse can identify and locate a piece of cheese several meters away entirely by smell, even though the concentration of airborne “cheese” molecules varies steeply over this distance. How the brain maintains perceptual stability across such widely ranging stimulus intensities remains a fundamental, unanswered question. The response properties of olfactory sensory neurons in the mouse’s nose may provide part of the answer. With each sniff, inhaled odorant molecules activate subsets of sensory neurons that each express a single type of odorant receptor. At low concentrations, when only a few odorant molecules are present, only those cells that express the most sensitive receptors for that particular odorant will be activated. However, many cells that express lower-affinity receptors will also be activated at higher concentrations, potentially degrading the odor representation. Crucially, the sensory neurons that express high-affinity receptors will always be activated earliest in the sniff, regardless of concentration. Could the mouse’s brain exploit this temporal structure to maintain stable odor representations despite changing odorant concentrations?

RATIONALE

To test this idea, we simultaneously recorded spiking activity from olfactory bulb (OB) mitral cells, which receive input from the olfactory sensory neurons, and from their cortical targets, principal neurons (PNs) in the piriform cortex (PCx), where odor identity is encoded. PNs form extensive, long-range “recurrent” excitatory synapses with each other in addition to forming excitatory synapses on PCx inhibitory interneurons. We hypothesized that this architecture enables the earliest activated—and therefore most selective—PCx PNs to rapidly inhibit less selective PCx PNs, helping to maintain stimulus specificity across odorant concentrations. We directly tested this idea by selectively expressing tetanus toxin in PCx PNs, blocking their ability to excite other PCx neurons but leaving them responsive to OB inputs.

RESULTS

In control mice, OB responses to different odors were more correlated and were more sensitive to differences in odor concentration than responses in PCx. Individual OB neurons fired bursts of action potentials, with odor-specific latencies and prolonged responses that were strongly concentration-dependent. By contrast, PCx PNs were briefly excited immediately after inhalation and then rapidly truncated by strong and sustained suppression. To identify the source of this suppression, we recorded from feedforward and feedback inhibitory interneurons in PCx. Feedforward interneurons, which are excited exclusively by OB inputs, exhibited little odor-evoked activity. By contrast, feedback interneurons, which are excited by PCx PNs but not by OB, showed robust and sustained spiking that mirrored PN suppression, indicating that PCx itself controls the timing and strength of its own suppression. We eliminated this intracortical communication by silencing recurrent excitatory synapses in PCx with tetanus toxin. This amplified and prolonged PCx PN responses, rendered their responses steeply concentration-dependent, and abolished the ability to stably predict odor identity across concentrations from PCx spiking activity.

DISCUSSION

The PCx cells that respond earliest after inhalation represent the most odorant-specific and concentration-invariant features of the odor. The extensive, long-range recurrent circuitry broadcasts their activation across PCx, recruiting strong, sustained global inhibition that then suppresses subsequent cortical activity. Recurrent circuitry therefore effectively amplifies the impact of the earliest arriving OB inputs and discounts the impact of less-selective inputs that arrive later. Thus, the recurrent circuitry in the PCx acts as a precisely timed gate to ensure that only the most salient information is relayed further into the brain to guide the mouse’s behavior.

Whenever a mouse inhales, volatile molecules activate odorant receptors in the nose, evoking sequences of activity in the olfactory bulb.

Bulb cells driven by the most specific receptors, which therefore best represent the odor stimulus (cheese), will always respond earliest. When this information is relayed to piriform cortex, activated principal neurons (red cells) recruit inhibitory neurons (green cells) that then suppress cortical responses to subsequent, less-specific olfactory bulb input (such as garlic, shoe, or flower), preserving the identity of the stimulus.

ILLUSTRATION BY JULIA KUHL

Abstract

Animals rely on olfaction to find food, attract mates, and avoid predators. To support these behaviors, they must be able to identify odors across different odorant concentrations. The neural circuit operations that implement this concentration invariance remain unclear. We found that despite concentration-dependence in the olfactory bulb (OB), representations of odor identity were preserved downstream, in the piriform cortex (PCx). The OB cells responding earliest after inhalation drove robust responses in sparse subsets of PCx neurons. Recurrent collateral connections broadcast their activation across the PCx, recruiting global feedback inhibition that rapidly truncated and suppressed cortical activity for the remainder of the sniff, discounting the impact of slower, concentration-dependent OB inputs. Eliminating recurrent collateral output amplified PCx odor responses rendered the cortex steeply concentration-dependent and abolished concentration-invariant identity decoding.

View Full Text