Modulation of sensory processing in the rodent olfactory system
Final Report Abstract
This project investigates the role of the cholinergic system in the detection and processing of sensory information in the earliest levels of the olfactory pathway; the olfactory bulb. The olfactory bulb receives centrifugal input from diverse brain centers, including cholinergic and GABAergic projections from the horizontal limb of the diagonal band of Broca (HDB). Here, we examined the influences of inputs originating from HDB on sensory input to and mitral/tufted (M/T) cell output from the olfactory bulb using in vivo imaging, electrophysiological and optogenetic approaches. First, we tested whether HDB stimulation affected odorant-evoked sensory inputs: presynaptic imaging from receptor neuron terminals displayed no HDB stimulation effect on presynaptic transmitter release. Next, we tested whether HDB stimulation affected postsynaptic activity by imaging from transgenic mice expressing GCaMP2 in MT and juxtaglomerular cells. HDB stimulation caused a transient increase in the odorant- and inhalation-evoked GCaMP2 signal. An extremely useful and unexpected finding allowed us to investigate output neuron activity even more selectively: by taking advantage of recently-developed tools that use viral vectors to introduce cre-dependent transgenes into select neurons in vivo we were able to investigate if specifically MT cell activity is modulated. Therefore we tested the HDB stimulation effect in Pcd21- cre animals in which a cre-dependent viral vector expressing GCaMP3.3 was injected into anterior piriform cortex. Also here HDB stimulation caused an increase in signal amplitudes that could be further subdivided into a phasic sniff evoked amplitude increase and a tonic increase in baseline fluorescence. Extracellular recordings from presumptive MT cells showed that HDB stimulation enhanced inhalation-evoked as well as spontaneous spiking. To specifically examine the influences of cholinergic (as opposed to GABA-ergic) inputs to the bulb, we selectively expressed channelrhodopsin (ChR2) in cholinergic HDB neurons using a cre-dependent viral vector injected into HDB of cre-ChAT mice. Subsequent optical activation of these neurons led to enhanced MT cell excitability in a manner qualitatively similar to that seen with electrical stimulation. These experiments are consistent with the hypothesis that cholinergic inputs to the olfactory bulb may enhance sensory-evoked MT responses and thus may be important in the attentional modulation of early olfactory processing. Ongoing experiments in awake behaving animals already demonstrated an increase in postsynaptic activity following exploratory sniffing as a measure of increased attention. Furthermore with the new tools at hand it will hopefully be possible to directly visualize the activation of modulatory inputs to the glomeruli in the awake animal.
Publications
-
Cholinergic Modulation of Neuronal Circuits in the Mammalian Olfactory Bulb. Society for Neuroscience Intermountain Chapter. Snowbird Ski & Summer Resort, Utah. Abstract book, p. 34
Rothermel M, Carey RM, Wachowiak M
-
Modulation of sensory processing in the rodent olfactory system GRK 736 Final Retreat Abschlußtreffen, Jugendgästehaus Münster, Am Aasee, Germany October 2010, Abstract book, p. 3
Rothermel M, Wachowiak M
-
Cholinergic Modulation of Neuronal Circuits in the Mammalian Olfactory Bulb. 33th Annual Meeting of the Association for Chemoreception Sciences AChemS 2011. St. Pete Beach, Florida. Abstract book, p. 99
Rothermel M, Carey RM, Wachowiak M
-
Cholinergic Modulation of Neuronal Circuits in the Mouse Olfactory Bulb. 41st annual meeting of the Society for Neuroscience (Neuroscience 2011), Washington DC, 475.28/II23
Rothermel M, Carey RM, Wachowiak M
