An energy budget for the olfactory glomerulus

Abstract

Energy demands are becoming recognized as an important constraint on neural signaling. The olfactory glomerulus provides a well defined system for analyzing this question. Odor stimulation elicits high-energy demands in olfactory glomeruli where olfactory axons converge onto dendrites of olfactory bulb neurons. We performed a quantitative analysis of the energy demands of each type of neuronal element within the glomerulus. This included the volumes of each element, their surface areas, and ion loads associated with membrane potentials and synaptic activation as constrained by experimental observations. In the resting state, there was a high-energy demand compared with other brain regions because of the high density of neural elements. The activated state was dominated by the energy demands of action potential propagation in afferent olfactory sensory neurons and their synaptic input to dendritic tufts, whereas subsequent dendritic potentials and dendrodendritic transmission contributed only a minor share of costs. It is proposed therefore that afferent input and axodendritic transmission account for the strong signals registered by 2-deoxyglucose and functional magnetic resonance imaging, although postsynaptic dendrites comprise at least one-half of the volume of the glomerulus. The results further suggest that presynaptic inhibition of the axon terminals by periglomerular cells plays an important role in limiting the range of excitation of the postsynaptic cells. These results provide a new quantitative basis for interpreting olfactory bulb activation patterns elicited by odor stimulation.

Figure 1.

Organization of the olfactory glomerulus. a, The neuronal compartments within a glomerulus. i, Unmyelinated ORN axon; ii, preterminal ORN axon; iii, presynaptic ORN axon terminal; iv, presynaptic and postsynaptic dendritic tuft of M, T, and PG cells; v, network of glial elements. b, Basic circuits in the olfactory glomerulus. i, ORN cilia project into the epithelium. Their membrane-bound odor receptors are activated through odor molecules (arrow). ii, ORN axons target M, T, and PG cells in the glomerulus via excitatory axodendritic synapses. A given axon might converge its input onto a single dendritic tuft (ii a) or distribute its input onto several receiving cells (ii b). iii, Dendrodendritic synapses between PG and M/T cells. PG cells make inhibitory contacts, and M/T cells make excitatory synapses. Dendrodendritic synapses might be established between cells that receive distinct (iii a) or similar (iii b) sensory input. iv, Synaptic input gives rise to dendritic action potentials/EPSPs.

Figure 2.

Simplifications of functional glomerular compartments for volume and surface estimations. a, Model of the average intraglomerular olfactory receptor neuron axon derived from morphological studies [inset, camera lucida reconstruction from a 21-d-old rat (Klenoff and Greer, 1998)]. The initial segment of the axon undergoes successive branching as shown. Overall branch length averages 200 μm, and there are ∼25 synaptic terminals (en passant varicosities and synaptic terminals) per axon. The area spanned by the axonal tree is relatively narrow. b, Morphology of the bulbar dendrites. Top left, Mitral cell dendritic tuft (courtesy of W. R. Chen). Bottom left, Branching pattern of mitral cell dendritic tuft. Top middle, Tufted cell tuft. Scale bar, 20 μm (courtesy of W. R. Chen). Bottom middle, Branching pattern of tufted cell dendritic tuft. Top right, Confocal reconstruction of biocytin-filled PG cell. Scale bar, 25 μm (from McQuiston and Katz, 2001). Bottom right, Branching pattern of PG cell dendritic tuft. c, Glomerular vascular supply. Left, Imaging of the capillary network within a single glomerulus by two-photon microscopy (from Chaigneau et al., 2003). Middle, Freehand representation of the capillary network. Right, Formal representation of the capillary network. d, Glomerular glial compartments. Far left, Distribution of astroglial sheets (dark gray) in glomerulus derived from two-photon microscopy (from Chao et al., 1997). Medium gray, Dendrites; light gray, sensory axons. Middle left, Simplified representation of glial process compartment (freehand representation). Middle right, Representation of sheet-like astroglial processes as volume-equivalent cylindrical edges of the compartment. Far right, Formal cube representation of a glial compartment.

Figure 3.

Energy demands of the activated glomerulus after electrophysiological stimulation of the olfactory nerve bundle. a, Distribution of ATP usage in the glomerulus for an activation of 1% of the ORN axons. b, Distribution of ATP usage in the glomerulus for an activation of 100% of the ORN axons.

Figure 4.

Odor stimulation of the glomerulus with one sniff per second. a, Absolute energy demands for each neuronal compartments as a function of odor concentration derived from the concentration–response model. Results are shown for the case that the costs, but not the effects of intraglomerular inhibition, are taken into account. b, Relative distribution of ATP usage in a for an activation of 1% of the ORNs. c, Relative distribution of ATP usage in a for an activation of 100% of the ORNs.

Figure 5.

The effect of intraglomerular inhibition on energy demands. a, Probability of mitral cell response during initial sniff when the effects of intraglomerular inhibition have not yet set in (dotted line) and during subsequent sniff for various degrees of intraglomerular inhibition (solid lines); the stronger the inhibition, the more gentle the slope. b, Effect of presynaptic versus dendrodendritic inhibition on the signaling cost.