Dendritic integration in olfactory bulb granule cells: Thresholds for lateral inhibition and role of active conductances upon simultaneous activation

Abstract

The inhibitory axonless olfactory bulb granule cells (GCs) form reciprocal dendrodendritic synapses with mitral and tufted cells via large spines, mediating recurrent and lateral inhibition. Rat GC dendrites are excitable by local Na+ spine spikes and global Ca2+- and Na+-spikes. To investigate the transition from local to global signaling without Na+ channel inactivation we performed simultaneous holographic two-photon uncaging in acute brain slices, along with whole-cell recording and dendritic Ca2+ imaging. Less than 10 coactive reciprocal spines were sufficient to generate diverse regional and global signals that also included local dendritic Ca2+- and Na+-spikes (D-spikes). Individual spines could sense the respective signal transitions as increments in Ca2+ entry. Dendritic integration was mostly linear until a few spines below global Na+-spike threshold, where often D-spikes set in. NMDARs strongly contributed to active integration, whereas morphological parameters barely mattered. In summary, thresholds for GC-mediated bulbar lateral inhibition are low.

Presynaptic NMDA receptors cooperate with local action potentials to implement activity-dependent GABA release from the reciprocal olfactory bulb granule cell spine

“…Evidence for GC spiking upon uniglomerular activation in vitro has been observed by several groups, including our own (e.g. Schoppa et al 1998, Egger 2008, Stroh et al 2012Burton & Urban 2015); moreover, we have shown recently that rather low numbers of coactivated spines on GC apical dendrites (< 10) are sufficient to elicit dendritic spiking (Mueller & Egger, 2020). In each schematic column, the depicted mitral cell and granule cell stand for the ensemble of all MCs and GCs belonging to the column.…”

“…With P r_GABA ≈ 0.3 and the probability for MC glutamate release on the order of P r_Glu ≈ 0.5 -0.75 (Egger et al 2005;Pressler & Strowbridge 2017) the efficiency of the entire reciprocal microcircuit can be estimated as P reciprocal = P r_Glu • P r_GABA ≈ 0.2, possibly informing future network models. The rather low P r_GABA observed here also implies that GC spines are likely to release with higher probabilities upon coincident global GC signalling (Ca 2+ spike or global action potential), due to substantially increased ∆Ca 2+ in the spine (Egger et al 2005;Egger 2008;Aghvami et al 2019;Mueller & Egger 2020). We predict this effect to boost both recurrent and lateral inhibition, as described below (Fig.…”

“…NMDARs play a crucial role in enabling supralinear dendritic integration in GCs, efficiently lowering the threshold for global spiking and thus also for lateral inhibition (Mueller & Egger 2020). Both GC NMDARs and Na v s are known to play a role specifically in discriminations between binary odorant mixtures in mice, since in the same behavioral paradigm GC-specific knock-down (in about ~ 50% of GCs) of the NMDAR-subunit GluN1 resulted in an increase in discrimination time of on average ~ ms, and knock-down of Na v s of ~ 85 ms versus control, while discriminations between pure odors were not affected (Abraham et al, 2010; Nunes & Kuner 2018).…”