Exploring Higher-Order Conceptual Learning in an Arthropod with a Large Multisensory Processing Center

Comparative cognition aims to understand the evolutionary history and current function of cognitive abilities in a variety of species with diverse natural histories. One characteristic often attributed to higher cognitive abilities is higher-order conceptual learning, such as the ability to learn concepts independent of stimuli—e.g., ‘same’ or ‘different’. Conceptual learning has been documented in honeybees and a number of vertebrates. Amblypygids, nocturnal enigmatic arachnids, are good candidates for higher-order learning because they are excellent associational learners, exceptional navigators, and they have large, highly folded mushroom bodies, which are brain regions known to be involved in learning and memory in insects. In Experiment 1, we investigate if the amblypygid Phrynus marginimaculatus can learn the concept of same with a delayed odor matching task. In Experiment 2, we test if Paraphrynus laevifrons can learn same/different with delayed tactile matching and nonmatching tasks before testing if they can transfer this learning to a novel cross-modal odor stimulus. Our data provide no evidence of conceptual learning in amblypygids, but more solid conclusions will require the use of alternative experimental designs to ensure our negative results are not simply a consequence of the designs we employed.

Novelty detection in early olfactory processing of the honey bee, Apis mellifera

Animals are constantly bombarded with stimuli, which presents a fundamental problem of sorting among pervasive uninformative stimuli and novel, possibly meaningful stimuli. We evaluated novelty detection behaviorally in honey bees as they position their antennae differentially in an air stream carrying familiar or novel odors. We then characterized neuronal responses to familiar and novel odors in the first synaptic integration center in the brain, the antennal lobes. We found that the neurons that exhibited stronger initial responses to the odor that was to be familiarized are the same units that later distinguish familiar and novel odors, independently of chemical identities. These units, including both projection neurons and local neurons, showed a decreased response to the familiar odor but an increased response to the novel odor. Our results suggest that the antennal lobe may assign a category of familiarity or novelty to an odor stimulus in addition to its chemical identity code. Therefore, the mechanisms for novelty detection may be present in early sensory processing, either as a result of local synaptic interaction or via feedback from higher brain centers.

Resolving different presynaptic activity patterns within single olfactory glomeruli of Xenopus laevis larvae

Olfactory sensing is generally organized into groups of similarly sensing olfactory receptor neurons converging into their corresponding glomerulus, which is thought to behave as a uniform functional unit. It is however unclear to which degree axons within a glomerulus show identical activity, how many converge into a glomerulus, and to answer these questions, how it is possible to visually separate them in live imaging. Here we investigate activity of olfactory receptor neurons and their axon terminals throughout olfactory glomeruli using electrophysiological recordings and rapid 4D calcium imaging. While single olfactory receptor neurons responsive to the same odor stimulus show a diversity of responses in terms of sensitivity and spontaneous firing rate on the level of the somata, their pre-synaptic calcium activity in the glomerulus is homogeneous. In addition, we could not observe the correlated spontaneous calcium activity that is found on the post-synaptic side throughout mitral cell dendrites and has been used in activity correlation imaging. However, it is possible to induce spatio-temporal presynaptic response inhomogeneities by applying trains of olfactory stimuli with varying amino acid concentrations. Automated region-of-interest detection and correlation analysis then visually distinguishes at least two axon subgroups per glomerulus that differ in odor sensitivity.

Human sleep consolidates allergic responses conditioned to the environmental context of an allergen exposure

Allergies are highly prevalent, and allergic responses can be triggered even in the absence of allergens due to Pavlovian conditioning to a specific cue. Here we show in humans suffering from allergic rhinitis that merely reencountering the environmental context in which an allergen was administered a week earlier is sufficient to trigger an allergic response—but only if participants had slept after allergen exposure. This context-conditioning effect was entirely absent when participants stayed awake the night after allergen exposure or were tested in a different context. Unlike in context conditioning, cue conditioning (to an odor stimulus) occurred independently of sleep, a differential pattern that is likewise observed for conditioning in the behavioral domain. Our findings provide evidence that allergic responses can be conditioned to contextual information alone, even after only a single-trial conditioning procedure, and that sleep is necessary to consolidate this rapidly acquired maladaptive response. The results unravel a mechanism that could explain part of the strong psychological impact on allergic responses.

Initial Characterization of a Subpopulation of Inherent Oscillatory Mammalian Olfactory Receptor Neurons

Published evidence suggests that inherent rhythmically active or “bursting” primary olfactory receptor neurons (bORNs) in crustaceans have the previously undescribed functional property of encoding olfactory information by having their rhythmicity entrained by the odor stimulus. In order to determine whether such bORN-based encoding is a fundamental feature of olfaction that extends beyond crustaceans, we patch-clamped bORN-like ORNs in mice, characterized their dynamic properties, and show they align with the dynamic properties of lobster bORNs. We then characterized bORN-like activity by imaging the olfactory epithelium of OMP-GCaMP6f mice. Next, we showed rhythmic activity is not dependent upon the endogenous OR by patching ORNs in OR/GFP mice. Lastly, we showed the properties of bORN-like ORNs characterized in mice generalize to rats. Our findings suggest encoding odor time should be viewed as a fundamental feature of olfaction with the potential to be used to navigate odor plumes in animals as diverse as crustaceans and mammals.

Temporally specific engagement of distinct neuronal circuits regulating olfactory habituation in Drosophila

Habituation is the process that enables salience filtering, precipitating perceptual changes that alter the value of environmental stimuli. To discern the neuronal circuits underlying habituation to brief inconsequential stimuli, we developed a novel olfactory habituation paradigm, identifying two distinct phases of the response that engage distinct neuronal circuits. Responsiveness to the continuous odor stimulus is maintained initially, a phase we term habituation latency and requires Rutabaga Adenylyl-Cyclase-depended neurotransmission from GABAergic Antennal Lobe Interneurons and activation of excitatory Projection Neurons (PNs) and the Mushroom Bodies. In contrast, habituation depends on the inhibitory PNs of the middle Antenno-Cerebral Track, requires inner Antenno-Cerebral Track PN activation and defines a temporally distinct phase. Collectively, our data support the involvement of Lateral Horn excitatory and inhibitory stimulation in habituation. These results provide essential cellular substrates for future analyses of the molecular mechanisms that govern the duration and transition between these distinct temporal habituation phases.Editorial note: This article has been through an editorial process in which the authors decide how to respond to the issues raised during peer review. The Reviewing Editor's assessment is that all the issues have been addressed (<xref ref-type="decision-letter" rid="SA1">see decision letter</xref>).

Extinction reverses olfactory fear-conditioned increases in neuron number and glomerular size

Although much work has investigated the contribution of brain regions such as the amygdala, hippocampus, and prefrontal cortex to the processing of fear learning and memory, fewer studies have examined the role of sensory systems, in particular the olfactory system, in the detection and perception of cues involved in learning and memory. The primary sensory receptive field maps of the olfactory system are exquisitely organized and respond dynamically to cues in the environment, remaining plastic from development through adulthood. We have previously demonstrated that olfactory fear conditioning leads to increased odorant-specific receptor representation in the main olfactory epithelium and in glomeruli within the olfactory bulb. We now demonstrate that olfactory extinction training specific to the conditioned odor stimulus reverses the conditioning-associated freezing behavior and odor learning-induced structural changes in the olfactory epithelium and olfactory bulb in an odorant ligand-specific manner. These data suggest that learning-induced freezing behavior, structural alterations, and enhanced neural sensory representation can be reversed in adult mice following extinction training.

Coding of odor stimulus features among secondary olfactory structures

Sensory systems must represent stimuli in manners dependent upon a wealth of factors, including stimulus intensity and duration. One way the brain might handle these complex functions is to assign the tasks throughout distributed nodes, each contributing to information processing. We sought to explore this important aspect of sensory network function in the mammalian olfactory system, wherein the intensity and duration of odor exposure are critical contributors to odor perception. This is a quintessential model for exploring processing schemes given the distribution of odor information by olfactory bulb mitral and tufted cells into several anatomically distinct secondary processing stages, including the piriform cortex (PCX) and olfactory tubercle (OT), whose unique contributions to odor coding are unresolved. We explored the coding of PCX and OT neuron responses to odor intensity and duration. We found that both structures similarly partake in representing descending intensities of odors by reduced recruitment and modulation of neurons. Additionally, while neurons in the OT adapt to odor exposure, they display reduced capacity to adapt to either repeated presentations of odor or a single prolonged odor presentation compared with neurons in the PCX. These results provide insights into manners whereby secondary olfactory structures may, at least in some cases, uniquely represent stimulus features.