Imaging olfactory network activity in a semi-intact nose-brain preparation: On the origin of spontaneous theta oscillations in the olfactory bulb

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Oscillations of neuronal activity at the theta rhythm (4-8 Hz) occur in many vertebrate neuronal ensembles, most famously within circuits linked to hippocampal areas. In the olfactory system, theta oscillations are known to enable proper olfactory coding in rats and humans. Their origin has been tied to respiratory activity which can effect sensory input through the nose mainly by mechanosensitive, olfactory and trigeminal pathways. Our observation of respiration-independent theta oscillations in the olfactory bulb in an decerebrated semi-intact nose-brain preparation indicates that such oscillations can occur spontaneously, without any sensory or centrifugal inputs. Our main working hypothesis is that breathing and therewith respiratory patterning of bulbar activity tap an intrinsic resonance of the olfactory bulb network; the spontaneous theta oscillations observed in the bulb of the nose-brain preparation are a correlate of this resonance and can be entrained by respiratory-like sensory input. To investigate this idea, we plan to combine the nose-brain preparation with our expertise in two-photon imaging techniques to explore network function at the single neuron and ensemble level and thereby unravel the origin of spontaneous theta and its interaction with sensory input in an intact network. A strong candidate mechanism for the origin of spontaneous theta oscillations is intrinsic pacemaking in a juxtaglomerular cell type, the external tufted cell (ETC), since ETCs are known to produce spontaneous bursts of activity within the theta frequency range. Thus the first step in this project is to fully establish Ca2+ population imaging within the glomerular layer in the nose-brain preparation, based on a pre-existing resonant scanning two-photon microscope system. Because the ETCs are located close to the bulbar surface and their bursts are known to yield substantial Ca2+ influx, ETC somatic signals are an excellent target for Ca2+ imaging. Next we will investigate the spontaneous activity of ETCs in parallel with local field potential recordings and test their contribution to the theta rhythm by pharmacological means. Finally we will explore the coupling between sensory stimulation with odorants, respiratory-like airflow and ETC activity, as well as the parallel activity of the principal mitral and tufted cells. Such an approach will allow us to investigate physiological patterns of activity in the nose-brain preparation and thus study releavant network properties in an in vitro system.In summary, we aim to elucidate the mechanism of the intrinsic olfactory bulb theta rhythm and how it interacts with both sensory input and olfactory bulb output by the principal neurons. Our investigations might also contribute to the understanding of theta coding in other brain areas.