Using relatively simple animals, and focusing primarily on olfaction, our unit combines electrophysiological, anatomical, behavioral, and genetic techniques to examine the ways intact neural circuits, driven by sensory stimuli, process information. In the past year, our research program has addressed several questions, among them: What mechanisms underlie information coding and decoding? How are multi-modal stimuli integrated into unified perceptions? And how are innate sensory preferences determined? Our work reveals basic mechanisms by which sensory information is transformed, stabilized, and compared as it makes its way through the nervous system.? ? Recently, we explored the neural coding of natural odor stimuli. A variety of sensory neural systems use spatio-temporal coding mechanisms to represent stimuli. These time-varying response patterns elicited by the stimuli sometimes endure longer than the stimulus itself. Can the temporal structure of a stimulus interfere with, or even disrupt the spatio-temporal structure of the neural representation? We investigated this potential confound in the locust olfactory system. When biologically relevant, non-pheromonal odors were presented in trains of nearly overlapping pulses, as occurs naturally in odor plumes, responses of first-order interneurons (the projection neurons) changed reliably, significantly, and often greatly with pulse position, as responses to one pulse interfered with subsequent responses. Thus, the temporal structure of the stimulus did indeed interfere with the temporal structure of the neural representation in these individual neurons. ? ? However, in the locust olfactory system (as in the vertebrate system), large numbers of individual projection neurons converge upon follower cells; coding appears to be achieved by means of an ensemble mechanism. Further, the oscillatory synchronization mechanism engaged by odorants results in a shutter-like parsing of projection neuron activity into a series of discrete time bins, each the duration of a single oscillatory cycle (about 50ms). We designed an analysis that was guided by our knowledge of how the olfactory system decodes the output of the projection neurons. Using a custom-built multi-unit amplifier, we made simultaneous recordings from large groups of projection neurons. ? ? Next, guided by follower neuron responses to the projection neuron ensemble, we devised a statistical means for combining the responses of an ensemble of projection neurons together, as a series of discrete 50ms time bins. By examining the projection neuron activity in this biologically relevant way, and using a novel statistical analysis, we found we could accurately classify the odorants, while also characterizing the temporal properties of the stimulus. Further, using an extracellular recording technique, we found that second-order, follower neurons (Kenyon cells) showed firing patterns consistent with the information in the projection neuron ensemble. Thus, we established that ensemble based spatio-temporal coding can disambiguate complex and potentially confounding temporally structured sensory stimuli, providing an invariant response to a stimulus presented in various ways.? ? To investigate mechanisms underlying the temporally invariant responses, we delivered repeated, rapid pulses of odors with timing designed to mimic features of natural plumes, while monitoring, in intact animals, neural activity in multiple locations: olfactory receptor neurons; first order interneurons; and second order interneurons. At each location, we sought to understand responses in terms of the interactions of plasticity occurring at earlier sites. We also sought to understand the potential value to the animal of these restructurings. ? ? We found interneuronal responses to natural forms of odor stimuli are shaped by at least two different, interacting, plastic mechanisms: rapid adaptation in the receptors, and relatively enduring facilitation of inhibition within their downstream targets. Peripheral adaptation appears to make the olfactory system relatively insensitive to stimuli that repeat very rapidly. Central facilitation of inhibition increases the reliability and sparseness of stimuli that are encountered repeatedly but relatively slowly. Further, these mechanisms constrain the projection neuron ensemble to provide relatively stable output to its downstream followers, thereby allowing the encoding of information about odor identity and concentration with firing patterns that are not confounded by the timing patterns of the stimulus.? ? How do the follower neurons decode this time-varying ensemble activity? Intracellular and extracellular recordings from Kenyon cells showed that their firing rates change dramatically throughout trains of odor pulses in a timing-dependent manner: for brief inter-pulse intervals, the great majority of action potentials fire at the beginning of the train, and again, following the train?s conclusion. We found the Kenyon cell firing threshold can be met when projection neurons fire at relatively low rates but are highly synchronized by the oscillatory mechanism of the antennal lobe (as occurs during the onset of the pulse train). On the other hand, the threshold can also be met when the instantaneous firing rate of the projection neuron ensemble is high in the absence of pronounced synchronization (as occurs following the offset of the train). ? ? Together, this work suggests that the non-associative plasticity elicited by odor plumes leads to responses in the projection neuron ensemble that combine an instantaneous report of sensory input with a record of recent input, allowing the extraction of high-level features.
| Assisi, Collins; Stopfer, Mark; Laurent, Gilles et al. (2007) Adaptive regulation of sparseness by feedforward inhibition. Nat Neurosci 10:1176-84 |
| Vislay-Meltzer, Rebecca L; Stopfer, Mark (2007) Olfactory coding: a plastic approach to timing precision. Curr Biol 17:R797-9 |
| Stopfer, Mark (2007) Olfactory processing: massive convergence onto sparse codes. Curr Biol 17:R363-4 |
| Kay, Leslie M; Stopfer, Mark (2006) Information processing in the olfactory systems of insects and vertebrates. Semin Cell Dev Biol 17:433-42 |
| Bazhenov, Maxim; Stopfer, Mark; Sejnowski, Terrence J et al. (2005) Fast odor learning improves reliability of odor responses in the locust antennal lobe. Neuron 46:483-92 |
| Brown, Stacey L; Joseph, Joby; Stopfer, Mark (2005) Encoding a temporally structured stimulus with a temporally structured neural representation. Nat Neurosci 8:1568-76 |
| Stopfer, Mark; Jayaraman, Vivek; Laurent, Gilles (2003) Intensity versus identity coding in an olfactory system. Neuron 39:991-1004 |
