Dendritic integration in olfactory bulb granule cells upon simultaneous multi-spine activation: Low thresholds for non-local spiking activity

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.