Unraveling the inner workings of reciprocal synapses with two-photon imaging and glutamate uncaging: Energy-efficient lateral inhibition in the olfactory bulb

Wednesday 10 July 2024, 4 pm

The vertebrate olfactory bulb processes olfactory stimuli within a two-stage network, with the stage first located in the glomerular input layer and the second in the external plexiform layer below. These subnetworks are bridged via the principal mitral and tufted cells; both strongly draw on dendrodendritic interactions, with the axonless inhibitory granule cells being the main players in the second stage. Granule cells direct their sole output towards the long lateral dendrites of mitral and tufted cells via reciprocal dendrodendritic synapses that are located within large spines. 

In spite or because of their apparently reduced anatomy, granule cells are capable of various modes of dendritic signalling. To dissect the reciprocal interactions, we are using two-photon Ca2+ imaging and uncaging of glutamate in acute slices of juvenile rat olfactory bulbs in conjunction with whole cell recordings and compartmental modeling. Our observations indicate that single inputs to the granule cell spine elicit a purely local sodium spike, which then engenders classical release of GABA via high-voltage activated Ca2+ channels. Thus the reciprocal spine functions as a mini-neuron that can provide recurrent inhibition independently of its ‘mother neuron’. Surprisingly, presynaptic NMDA receptors also play an essential role for GABA release from the spine. The unique cooperative action of presynaptic NMDARs with respect to GABAergic output allows to implement non-topographical, activity-dependent lateral inhibition between glomerular columns across the bulb. Such a mechanism not only explains hitherto enigmatic observations on granule cell interactions but may provide an elegant, sparse solution to combinatorial percept synthesis in a sensory system with many receptor channels. 

Wednesday 10 July 2024, 4 pm
Huygens building HG 00.303