The mammalian olfactory bulb (OB), the first center of synaptic integration in the olfactory systems, receives massive cholinergic inputs from the basal forebrain and dense noradrenergic innervations from the locus coeruleus, both of which have profound effects on odor processing as well as olfactory learning and memory. However, the effects of acetylcholine (ACh) and norepinephrine (NE) have not been clearly distinguished. Given the important roles of cholinergic and noradrenergic modulation in the olfactory bulb, achieving clear functional dissociation among the roles of these two modulators is not trivial and is required for a mechanistic and integrated understanding of olfactory information processing in the brain. Using detailed biophysical simulations of granule cells, the major interneurons in the olfactory bulb, both alone and embedded in a microcircuit with mitral cells (MCs), the principal output neurons of olfactory bulb, we demonstrated computationally for the first time that the effects of ACh and NE on olfactory bulb function are both distinct and functionally complementary to one another. While ACh increases MC spike synchronization and sharpens MC firing rate representation, NE mainly modulates the neuronal signal-to-noise ratio (S/N) and can regulate cholinergic function. Co-application of ACh and NE sharpens MC tuning, improves the S/N ratio and enhances spike synchronization among mitral cells. Our main conclusions are that ACh is particularly important for odor discrimination and sensory information encoding via a spike-timing code, while NE is more important for odor detection. Therefore, this work is significant in understanding the cholinergic and noradrenergic function in the olfactory bulb and offers important specific and testable hypotheses for future work.
Figure Legend: The effects of acetylcholine (ACh) and norepinephrine (NE) in the olfactory bulb are both distinct and complementary to each other. ACh modulation increases mitral cell (MC) spike synchronization and sharpens odor representation by suppressing the weakly activated MCs. By comparison, NE modulation increases the signal-to-noise (S/N) ratio by suppressing MC spontaneous activities. Simultaneous activation of ACh and NE leads to highly synchronized MCs, large S/N ratio and highly tuned MC responses with little overlap between different odors.
J Neurophysiol. 2015 Dec;114(6):3177-200.
Li G1, Linster C2, Cleland TA3.[expand title=”Show Affiliations”]
- Department of Psychology, Cornell University, Ithaca, New York; [email protected]
- Department of Neurobiology and Behavior, Cornell University, Ithaca, New York.
- Department of Psychology, Cornell University, Ithaca, New York; [/expand]
Olfactory bulb granule cells are modulated by both acetylcholine (ACh) and norepinephrine (NE), but the effects of these neuromodulators have not been clearly distinguished. We used detailed biophysical simulations of granule cells, both alone and embedded in a microcircuit with mitral cells, to measure and distinguish the effects of ACh and NE on cellular and microcircuit function. Cholinergic and noradrenergic modulatory effects on granule cells were based on data obtained from slice experiments; specifically, ACh reduced the conductance densities of the potassium M current and the calcium-dependent potassium current, whereas NE nonmonotonically regulated the conductance density of an ohmic potassium current. We report that the effects of ACh and NE on granule cell physiology are distinct and functionally complementary to one another. ACh strongly regulates granule cell firing rates and after potentials, whereas NE bidirectionally regulates subthreshold membrane potentials. When combined, NE can regulate the ACh-induced expression of after depolarizing potentials and persistent firing. In a microcircuit simulation developed to investigate the effects of granule cell neuromodulation on mitral cell firing properties, ACh increased spike synchronization among mitral cells, whereas NE modulated the signal-to-noise ratio. Coapplication of ACh and NE both functionally improved the signal-to-noise ratio and enhanced spike synchronization among mitral cells. In summary, our computational results support distinct and complementary roles for ACh and NE in modulating olfactory bulb circuitry and suggest that NE may play a role in the regulation of cholinergic function.
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