Mark Stopfer

Impaired odour discrimination on desynchronization of odour-encoding neural assemblies

Stimulus-evoked oscillatory synchronization of neural assemblies has been described in the olfactory and visual systems of several vertebrates and invertebrates. In locusts, information about odour identity is contained in the timing of action potentials in an oscillatory population response, suggesting that oscillations may reflect a common reference for messages encoded in time. Although the stimulus-evoked oscillatory phenomenon is reliable, its roles in sensation, perception, memory formation and pattern recognition remain to be demonstrated — a task requiring a behavioural paradigm. Using honeybees, we now demonstrate that odour encoding involves, as it does in locusts, the oscillatory synchronization of assemblies of projection neurons and that this synchronization is also selectively abolished by picrotoxin, an antagonist of the GABAA (γ-aminobutyric acid) receptor. By using a behavioural learning paradigm, we show that picrotoxin-induced desynchronization impairs the discrimination of molecularly similar odorants, but not that of dissimilar odorants. It appears, therefore, that oscillatory synchronization of neuronal assemblies is functionally relevant, and essential for fine sensory discrimination. This suggests that oscillatory synchronization and the kind of temporal encoding it affords provide an additional dimension by which the brain could segment spatially overlapping stimulus representations.

Short-term memory in olfactory network dynamics

Neural assemblies in a number of animal species display self-organized, synchronized oscillations in response to sensory stimuli in a variety of brain areas.. In the olfactory system of insects, odour-evoked oscillatory synchronization of antennal lobe projection neurons (PNs) is superimposed on slower and stimulus-specific temporal activity patterns. Hence, each odour activates a specific and dynamic projection neuron assembly whose evolution during a stimulus is locked to the oscillation clock. Here we examine, using locusts, the changes in population dynamics of projection-neuron assemblies over repeated odour stimulations, as would occur when an animal first encounters and then repeatedly samples an odour for identification or localization. We find that the responses of these assemblies rapidly decrease in intensity, while they show a marked increase in spike time precision and inter-neuronal oscillatory coherence. Once established, this enhanced precision in the representation endures for several minutes. This change is stimulus-specific, and depends on events within the antennal lobe circuits, independent of olfactory receptor adaptation: it may thus constitute a form of sensory memory. Our results suggest that this progressive change in olfactory network dynamics serves to converge, over repeated odour samplings, on a more precise and readily classifiable odour representation, using relational information contained across neural assemblies.

Model of Transient Oscillatory Synchronization in the Locust Antennal Lobe

Transient pairwise synchronization of locust antennal lobe (AL) projection neurons (PNs) occurs during odor responses. In a Hodgkin-Huxley-type model of the AL, interactions between excitatory PNs and inhibitory local neurons (LNs) created coherent network oscillations during odor stimulation. GABAergic interconnections between LNs led to competition among them such that different groups of LNs oscillated with periodic Ca(2+) spikes during different 50-250 ms temporal epochs, similar to those recorded in vivo. During these epochs, LN-evoked IPSPs caused phase-locked, population oscillations in sets of postsynaptic PNs. The model shows how alternations of the inhibitory drive can temporally encode sensory information in networks of neurons without precisely tuned intrinsic oscillatory properties.

Model of Cellular and Network Mechanisms for Odor-Evoked Temporal Patterning in the Locust Antennal Lobe

Locust antennal lobe (AL) projection neurons (PNs) respond to olfactory stimuli with sequences of depolarizing and hyperpolarizing epochs, each lasting hundreds of milliseconds. A computer simulation of an AL network was used to test the hypothesis that slow inhibitory connections between local neurons (LNs) and PNs are responsible for temporal patterning. Activation of slow inhibitory receptors on PNs by the same GABAergic synapses that underlie fast oscillatory synchronization of PNs was sufficient to shape slow response modulations. This slow stimulus- and neuron-specific patterning of AL activity was resistant to blockade of fast inhibition. Fast and slow inhibitory mechanisms at synapses between LNs and PNs can thus form dynamical PN assemblies whose elements synchronize transiently and oscillate collectively, as observed not only in the locust AL, but also in the vertebrate olfactory bulb.

Odor-Evoked Neural Oscillations in Drosophila Are Mediated by Widely Branching Interneurons

Stimulus-evoked oscillatory synchronization of neurons has been observed in a wide range of species. Here, we combined genetic strategies with paired intracellular and local field potential (LFP) recordings from the intact brain of Drosophila to study mechanisms of odor-evoked neural oscillations. We found common food odors at natural concentrations elicited oscillations in LFP recordings made from the mushroom body (MB), a site of sensory integration and analogous to the vertebrate piriform cortex. The oscillations were reversibly abolished by application of the GABAa blocker picrotoxin. Intracellular recordings from local and projection neurons within the antennal lobe (AL) (analogous to the olfactory bulb) revealed odor-elicited spikes and subthreshold membrane potential oscillations that were tightly phase locked to LFP oscillations recorded downstream in the MBs. These results suggested that, as in locusts, odors may elicit the oscillatory synchronization of AL neurons by means of GABAergic inhibition from local neurons (LNs). An analysis of the morphologies of genetically distinguished LNs revealed two populations of GABAergic neurons in the AL. One population of LNs innervated parts of glomeruli lacking terminals of receptor neurons, whereas the other branched more widely, innervating throughout the glomeruli, suggesting that the two populations might participate in different neural circuits. To test the functional roles of these LNs, we used the temperature-sensitive dynamin mutant gene shibire to conditionally and reversibly block chemical transmission from each or both of these populations of LNs. We found only the more widely branching population of LNs is necessary for generating odor-elicited oscillations.

Temporally Diverse Firing Patterns in Olfactory Receptor Neurons Underlie Spatiotemporal Neural Codes for Odors

Odorants are represented as spatiotemporal patterns of spikes in neurons of the antennal lobe (AL; insects) and olfactory bulb (OB; vertebrates). These response patterns have been thought to arise primarily from interactions within the AL/OB, an idea supported, in part, by the assumption that olfactory receptor neurons (ORNs) respond to odorants with simple firing patterns. However, activating the AL directly with simple pulses of current evoked responses in AL neurons that were much less diverse, complex, and enduring than responses elicited by odorants. Similarly, models of the AL driven by simplistic inputs generated relatively simple output. How then are dynamic neural codes for odors generated? Consistent with recent results from several other species, our recordings from locust ORNs showed a great diversity of temporal structure. Furthermore, we found that, viewed as a population, many response features of ORNs were remarkably similar to those observed within the AL. Using a set of computational models constrained by our electrophysiological recordings, we found that the temporal heterogeneity of responses of ORNs critically underlies the generation of spatiotemporal odor codes in the AL. A test then performed in vivo confirmed that, given temporally homogeneous input, the AL cannot create diverse spatiotemporal patterns on its own; however, given temporally heterogeneous input, the AL generated realistic firing patterns. Finally, given the temporally structured input provided by ORNs, we clarified several separate, additional contributions of the AL to olfactory information processing. Thus, our results demonstrate the origin and subsequent reformatting of spatiotemporal neural codes for odors.

Recent dynamics in olfactory population coding

Recent studies of the olfactory bulb (vertebrates) and antennal lobe (insects) have elucidated how odor information is represented by the identity, synchronization, slow temporal dynamics and position of active neurons in an ensemble. Odor representations are dynamically reorganized both during the course of a stimulus and with experience. These results provide new insights into the logic of odor representations and dynamical network computations.

Functional Analysis of a Higher Olfactory Center, the Lateral Horn

The lateral horn (LH) of the insect brain is thought to play several important roles in olfaction, including maintaining the sparseness of responses to odors by means of feedforward inhibition, and encoding preferences for innately meaningful odors. Yet relatively little is known of the structure and function of LH neurons (LHNs), making it difficult to evaluate these ideas. Here we surveyed >250 LHNs in locusts using intracellular recordings to characterize their responses to sensory stimuli, dye-fills to characterize their morphologies, and immunostaining to characterize their neurotransmitters. We found a great diversity of LHNs, suggesting this area may play multiple roles. Yet, surprisingly, we found no evidence to support a role for these neurons in the feedforward inhibition proposed to mediate olfactory response sparsening; instead, it appears that another mechanism, feedback inhibition from the giant GABAergic neuron, serves this function. Further, all LHNs we observed responded to all odors we tested, making it unlikely these LHNs serve as labeled lines mediating specific behavioral responses to specific odors. Our results rather point to three other possible roles of LHNs: extracting general stimulus features such as odor intensity; mediating bilateral integration of sensory information; and integrating multimodal sensory stimuli.

Neural Dynamics, Oscillatory Synchronisation, and Odour Codes

Years of productive research examining insect olfaction have revealed numerous important functional and organisational features of the antennal lobe (AL), as described throughout this volume. Recent advances in techniques for simultaneously monitoring the activities of multiple neurons have revealed another important fact about the AL, that its dynamics act to coordinate large numbers of olfactory interneurons so that, when processing odorants, many of them oscillate in synchrony. The effect of this coherent neural activity is surprisingly powerful: it enables the AL to encode odour information in time. We will summarise here experimental results suggesting that, in insects, essential information about odour quality is indeed conveyed not only by the identity of activated neurons (a spatial pattern), but also by the temporal patterns of their odour responses relative to a common time base, the oscillatory ensemble activity.

Dynamic Encoding of Odors With Oscillating Neuronal Assemblies in the Locust Brain

The computational rules followed by the brain to encode complex, multidimensional stimuli such as natural odors are not well understood. In this review, we summarize results obtained in the olfactory system of an insect and present a hypothesis for odor representation in the brain. We propose that individual odors are represented by ensembles of neurons that are distributed both in space (the specific identities of the neurons forming an ensemble) and in time (the time at which each neuron participates in the ensemble response). In addition, we discuss the potential roles that periodic synchronization (oscillations) might play in this complex process.