Dendritic integration in olfactory bulb granule cells upon simultaneous multi-spine activation: Low thresholds for non-local spiking activity
Müller, Max; Egger, Veronica (2020), Dendritic integration in olfactory bulb granule cells upon simultaneous multi-spine activation: Low thresholds for non-local spiking activity, Dryad, Dataset, https://doi.org/10.5061/dryad.mgqnk98wq
The inhibitory axonless olfactory bulb granule cells form reciprocal dendrodendritic synapses with mitral and tufted cells via large spines, mediating recurrent and lateral inhibition. As a case in point for dendritic transmitter release, rat granule cell dendrites are highly excitable, featuring local Na+ spine spikes and global Ca2+- and Na+-spikes. To investigate the transition from local to global signaling we performed holographic, simultaneous two-photon uncaging of glutamate at up to twelve granule cell spines, along with whole-cell recording and dendritic two-photon Ca2+ imaging in acute juvenile rat brain slices. Coactivation of less than ten reciprocal spines was sufficient to generate diverse regenerative signals that included regional dendritic Ca2+-spikes and dendritic Na+-spikes (D-spikes). Global Na+-spikes could be triggered in one third of granule cells. Individual spines and dendritic segments sensed the respective signal transitions as increments in Ca2+ entry. Dendritic integration as monitored by the somatic membrane potential was mostly linear until a threshold number of spines was activated, where often D-spikes along with supralinear summation set in. As to the mechanisms supporting active integration, NMDA receptors strongly contributed to all aspects of supralinearity, followed by dendritic voltage-gated Na+- and Ca2+-channels, whereas local Na+ spine spikes as well as morphological parameters barely mattered.
Because of the low numbers of coactive spines required to trigger dendritic Ca2+ signals and thus possibly lateral release of GABA onto mitral and tufted cells, we predict that thresholds for granule cell-mediated bulbar lateral inhibition are low. Moreover, D-spikes could provide a plausible substrate for granule cell-mediated gamma oscillations.
Electrophysiology, 2P Ca2+ imaging, 2P holographic multi-site glutamate uncaging. Data was recorded in MES (Femtonics) and analyzed in Igor (Wavemetrics) and Excel.