Coincidence Detection within the Excitable Rat Olfactory Bulb Granule Cell Spines

Abstract

In the mammalian olfactory bulb, the inhibitory axonless granule cells (GCs) feature reciprocal synapses that interconnect them with the principal neurons of the bulb, mitral, and tufted cells. These synapses are located within large excitable spines that can generate local action potentials (APs) upon synaptic input ("spine spike"). Moreover, GCs can fire global APs that propagate throughout the dendrite. Strikingly, local postsynaptic Ca 2ϩ entry summates mostly linearly with Ca 2ϩ entry due to coincident global APs generated by glomerular stimulation, although some underlying conductances should be inactivated. We investigated this phenomenon by constructing a compartmental GC model to simulate the pairing of local and global signals as a function of their temporal separation ⌬t. These simulations yield strongly sublinear summation of spine Ca 2ϩ entry for the case of perfect coincidence ⌬t ϭ 0 ms. Summation efficiency (SE) sharply rises for both positive and negative ⌬t. The SE reduction for coincident signals depends on the presence of voltage-gated Na ϩ channels in the spine head, while NMDARs are not essential. We experimentally validated the simulated SE in slices of juvenile rat brain (both sexes) by pairing two-photon uncaging of glutamate at spines and APs evoked by somatic current injection at various intervals ⌬t while imaging spine Ca 2ϩ signals. Finally, the latencies of synaptically evoked global APs and EPSPs were found to correspond to ⌬t Ϸ 10 ms, explaining the observed approximately linear summation of synaptic local and global signals. Our results provide additional evidence for the existence of the GC spine spike.Here we investigate the interaction of local synaptic inputs and global activation of a neuron by a backpropagating action potential within a dendritic spine with respect to local Ca 2ϩ signaling. Our system of interest, the reciprocal spine of the olfactory bulb granule cell, is known to feature a special processing mode, namely, a synaptically triggered action potential that is restricted to the spine head. Therefore, coincidence detection of local and global signals follows different rules than in more conventional synapses. We unravel these rules using both simulations and experiments and find that signals coincident within ϷϮ7 ms around 0 ms result in sublinear summation of Ca 2ϩ entry because of synaptic activation of voltage-gated Na ϩ channels within the spine.

Functional Specialization of Interneuron Dendrites: Identification of Action Potential Initiation Zone in Axonless Olfactory Bulb Granule Cells

“…However, Na V 1.2 also appears to be expressed at high levels in distal segments of the GC apical dendrite, including in spine heads (Nunes and Kuner, 2018) This indicator, therefore, may reflect Na ϩ channels involved both in spike initiation and active propagation of APs into the distal dendrites of GCs. Multiple imaging-based studies have focused on the functional role of voltage-gated Na ϩ channels in distal GC dendrites and on dendritic spines (Zelles et al, 2006;Egger, 2008;Bywalez et al, 2015;Aghvami et al, 2019). Because of their different focus, these prior studies did not addressed the question of where APs initiate in GCs though Egger (2008) did report increased fractional changes in Ca 2ϩ indicator responses as the sampling position along the apical dendrite was moved to more distal positions, consistent with our findings.…”

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

“…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.…”

“…Fig. 5A shows a simulation of the postsynaptic NMDAR-and HVACC-mediated Ca 2+ currents (based on the detailed NEURON model described in Aghvami et al 2019, see Methods) which illustrates that the local AP causes a transient boosting of the NMDAR Ca 2+ current because of further relief of the Mg 2+ block during the upstroke and overshoot of the spine spike.…”

“…This conservative method prevents false negatives due to lacking sensitivity in individual trials in the presence of the drug. (Destexhe et al 1998), while the HVACC model is adopted from Hemond et al 2008, with adjustments based on own Ca 2+ current recordings (see Aghvami et al 2019). For the simulations shown in Fig.…”

Young adult-born neurons improve odor coding by mitral cells

“…To date, the role of GCs in general and particularly abGCs in shaping MCs activity remains unclear 58 – 60 . One idea is that GCs predict the input from olfactory receptor neurons and establish a counterbalancing inhibitory activity that (incompletely) mirrors the activity of their cognate MCs inputs 61 .…”