Unique Functional Properties of Mature Adult-Born Neurons in the Mouse Olfactory Bulb

Abstract

The rodent olfactory bulb (OB) is continuously supplied with adult-born cells maturing into GABAergic neurons. Using in vivo ratiometric Ca 2+ imaging to readout ongoing and sensory-driven activity, we asked whether mature adult-born cells (mABCs) in the glomerular layer of the bulb become functionally identical to resident GABAergic (Res GABA) neurons. In awake head-restrained mice the two cell populations differed significantly in terms of ongoing spontaneous activity, with 24% of mABCs contributing to a strongly active cell cluster, absent among Res GABA cells. Odor-evoked responses of mABCs were sparse, less reliable, and had smaller amplitudes compared with Res GABA cells. The opposite was seen under anesthesia, with response reliability increasing and response size of mABCs becoming larger than that of Res GABA cells. Furthermore, ongoing activity of mABCs showed increased sensitivity to ketamine/xylazine and was selectively blocked by the antagonist of serotonin receptors methysergide. These functional features of mABCs clearly distinguish them from other OB interneurons.

Neuronal silence as a prosurvival factor for adult-born olfactory bulb interneurons

“…To do so, we analyzed activity patterns of subsequently eliminated cells at DBDs 10, 8, 6, 4, and 2 and compared them with activity patterns of surviving abJGNs recorded in the same mice at the same time points. Previously, we have documented the ubiquitous presence of spontaneous Ca 2+ transients in the Twitch-2B + abJGNs and shown, using a voltage-gated Na + channel blocker tetrodotoxin, that Twitch-2B + abJGNs can be considered active (i.e., spiking) when their Twitch-2B ratio is above 2.4 and non-active (i.e., electrically silent) when their Twitch-2B ratio is below 2.0 ( Fomin-Thunemann et al., 2020 ; Maslyukov et al., 2018 ). Here, we used this knowledge to analyze the following six parameters ( Note S1 ): basal Twitch-2B ratio, maximum Twitch-2B ratio, maximum ΔR/R amplitude of ongoing Ca 2+ transients, the fraction of time spent in the active state (Twitch-2B ratio >2.4), AUC/second ( Figure 6 E), and the fraction of time spent in the silent state (Twitch-2B ratio <2.0).…”

Enhanced endogenous activity predicts elimination of adult-born neurons in the mouse olfactory bulb

“…The parameters of odor-evoked responsiveness analyzed in this study (maximum response amplitude and AUC), were also not able to differentiate between surviving and subsequently eliminated cells. We cannot, however, exclude the possibility that other properties (e.g., odor selectivity or the stability of odor responses; Livneh et al, 2014;Wallace et al, 2017;Fomin-Thunemann et al, 2020) differ in these two groups of cells. In this study, we took the cells' odor-responsiveness as a read-out of its functional integration into surrounding neural circuitry.…”

“…spiking) when their Twitch-2B ratio is above 2.4 and non-active (i.e. electrically silent) when their Twitch-2B ratio is below 2.0 (Fomin-Thunemann et al, 2020;Maslyukov et al, 2018). In the current study, we used this knowledge to analyze the following parameters: basal Twitch-2B ratio, maximum Twitch-2B ratio, maximum ΔR/R amplitude of spontaneous Ca 2+ transients, the fraction of time spent in the active state (i.e., Twitch-2B ratio above 2.4), AUC/second (as illustrated in Fig.…”

Endogenous but not sensory-driven activity controls migration, morphogenesis and survival of adult-born neurons in the mouse olfactory bulb

“…The spontaneous Ca 2+ transients were recorded in awake mice. Prior to imaging sessions, the mice were trained for head fixation for 10-12 days, as described in (13). Spontaneous Ca 2+ transients of adult-born JGCs were recorded at 12 dpi continuously for 2 minutes with a frame rate of 7-10 Hz.…”

“…Generated in the subventricular zone (SVZ) of the lateral ventricle (7,8), adult-born cells migrate along the rostral migratory stream (RMS) into the OB and differentiate into local GABAergic interneurons: granule cells (GCs) in the granule cell layer and juxtaglomerular cells (JGCs) in the glomerular layer (9) of the bulb. Many molecules including GABA, glutamate, dopamine, serotonin, BDNF, and cAMP response element-binding protein (CREB) influence the adult OB neurogenesis (10)(11)(12)(13)(14). Yet, the exact mechanisms underlying the migration, maturation, and incorporation of adult-born neurons into the existent OB circuitry remain unclear.…”