From the top down: flexible reading of a fragmented odor map

Abstract

Animals that depend on smell for communication and survival extract multiple pieces of information from a single complex odor. Mice can collect information on sex, genotype, health and dietary status from urine scent marks, a stimulus made up of hundreds of molecules. This ability is all the more remarkable considering that natural odors are encountered against varying olfactory backgrounds; the olfactory system must therefore provide some mechanism for extracting the most relevant information. Here we discuss recent data indicating that the readout of olfactory input by mitral cells in the olfactory bulb can be modified by behavioral context. We speculate that the olfactory cortex plays a key role in tuning the readout of olfactory information from the olfactory bulb.

Figure 1

Drawing by Ramón y Cajal showing the olfactory system from olfactory epithelium to olfactory cortex. He labeled the olfactory sensory neurons (A) and sustentacular cells (h) in the olfactory epithelium; glomeruli (B), mitral cells (C), tufted cells (a), granule cells (D), the lateral olfactory tract (E) in the olfactory bulb; and the olfactory cortex (F). Note the arrows that he drew implying the flow of information through the circuit. The fibers at the top of the drawing (what he called centrifugal fibers) have arrows that imply information flow in the direction of the olfactory bulb. These centrifugal fibers are now known to be centrifugal with respect to the olfactory cortex and neuromodulatory centers where they originate. Reproduced with permission from the original at the Cajal Institute CSIC, Madrid.

Figure 2

Near coincident activation of centrifugal fibers from olfactory cortex and depolarization of MT cells elicits enhanced dendrodendritic inhibition. (a). Diagram showing the arrangement of olfactory bulb and olfactory cortex where MT cells send information to cortex where principal neurons in turn feed back onto granule cells. In addition to centrifugal collaterals from olfactory cortex that innervate the proximal dendrites of granule cells, the diagram shows centrifugal feedback from one of the neuromodulatory brain areas (the cholinergic basal forebrain). Note that the lateral dendrites of the MT cells contact the distal dendrites of the granule cells where they form the reciprocal synapse shown schematically in figure (c). (b). Data from Balu and co-workers show that removal of Mg²⁺ from the extracellular solution releases block of the NMDA receptors thereby allowing large dendrodendritic inhibitory currents (outward currents) to a 20 mV depolarization of the mitral cell. These dendrodendritic responses were blocked by the NMDAR blocker D-APV. (c). Top panels: Schematic representation of the function of reciprocal synapses where MT cells release glutamate to excite distal dendrites of granule cells. The bottom panels display data from Balu and co-workers showing that near coincident mitral cell depolarization (dendrodendritic inhibition-DDI) and anterior piriform cortex (APC) stimulation evokes outward inhibitory currents in mitral cells. Example responses to voltage-clamp depolarization alone (DDI, to +20 mV, 2 ms duration; left) and both intracellular depolarization and APC stimulation (DDI + APC, right) are shown. The diagram at the top shows that APC stimulation releases Mg²⁺ block of NMDA receptors in granule cells thereby allowing synaptic activation of the granule cell distal synapse and release of GABA onto the mitral cell, in turn eliciting outward inhibitory currents in the mitral cell.

Figure 3

Divergence of MT cell responses during learning to discriminate between two novel odors. The data reproduced from Doucette and Restrepo show that MT cells undergo a profound change in odor responsiveness during a session where animals learn to associate one odor with reward (rewarded) and another with no reward (unrewarded). (a). A thirsty mouse learns to associate the reinforced odor with a water reward and the unreinforced odor with no reward. The mouse must lick on a metal tube for two seconds when presented with the rewarded odor to obtain the water reward. Rasters below the mouse show the responsiveness of a suspected mitral cell to the reinforced odor and unreinforced odor during the first block of 20 trials (10 reinforced and 10 unreinforced) and for block 6 (trials 100 to 120). During the first block the mouse responds randomly to the two odors while in block 6 the mouse is responding correctly ~80% of the time. (b). Examples of changes in odor responsiveness throughout the learning session. Red denotes rewarded odor and blue denotes unrewarded odor. The ordinate shows the change in the number of spikes fired in a 0.15 sec interval elicited by addition of odor. The top panel shows odor responsiveness of a unit that responded differentially to the two odors from the onset of the session. This was rare (observed in 2 of 660 units). The bottom panel shows odor responsiveness of the cell whose responses are shown in (a). This cell developed a transient differential response to the two odors. This is representative of 93 of 660 units. (c). Pie charts showing the percent of units that responded to odors (red), and those that responded differently to the two odors (green). The first block is the first 20 trials in the session and the best block is the 20 trials during the block where the unit displayed the largest difference in odor-evoked firing between reinforced and unreinforced odors.