ACTIVITY-DEPENDENT LATERAL INHIBITION IN THE MOUSE OLFACTORY BULB

Lateral inhibition is a circuit motif found throughout the nervous system that often generates contrast enhancement and center-surround receptive fields. While widespread lateral inhibition of mitral cells (the principal output neurons of the bulb) is mediated by granule cells (inhibitory interneurons), due to the distributed representation of odorant-evoked activity it is currently unclear how this inhibition is specified or what functions it mediates. Given the reciprocal nature of the connection between mitral and granule cells, mitral cells that are the targets of lateral inhibition (postsynaptic) are able to modulate the activity of the granule cells mediating this lateral inhibition. This led us to hypothesize that lateral inhibition could be modulated by the activity of both pre- as well as postsynaptic mitral cells. I first characterize the lateral interactions between mitral cells and show that the effectiveness of lateral inhibition between them is dependent on the activity of the postsynaptic neuron such that lateral inhibition is only able to reduce the firing rate within a specific range of postsynaptic firing rates. I call this activity-dependent lateral inhibition. I then investigated this novel form of inhibition further and provide evidence indicating that it results from cooperative activation of the inhibitory granule cells.I investigated the mechanism and functional implications of these physiological results further using computational techniques. First, I show that integration of activity between pre- and postsynaptic mitral cells within a granule cell is sufficient to result in activity-dependent inhibition. I then used this model to show that activity-dependent inhibition is able to enhance the contrast and decorrelate initially similar input patterns to the network in a spatially independent manner. These results provide evidence for a novel form of neuronal interaction dependent on the activity of neurons within the network which could have important functional implications in olfaction as well as other brain areas.