Coordinated electrical activity in the olfactory bulb gates the oscillatory entrainment of entorhinal networks in neonatal mice

Abstract

Although the developmental principles of sensory and cognitive processing have been extensively investigated, their synergy has been largely neglected. During early life, most sensory systems are still largely immature. As a notable exception, the olfactory system is functional at birth, controlling mother–offspring interactions and neonatal survival. Here, we elucidate the structural and functional principles underlying the communication between olfactory bulb (OB) and lateral entorhinal cortex (LEC)—the gatekeeper of limbic circuitry—during neonatal development. Combining optogenetics, pharmacology, and electrophysiology in vivo with axonal tracing, we show that mitral cell–dependent discontinuous theta bursts in OB drive network oscillations and time the firing in LEC of anesthetized mice via axonal projections confined to upper cortical layers. Acute pharmacological silencing of OB activity diminishes entorhinal oscillations, whereas odor exposure boosts OB–entorhinal coupling at fast frequencies. Chronic impairment of olfactory sensory neurons disrupts OB–entorhinal activity. Thus, OB activity shapes the maturation of entorhinal circuits.

Neural Correlates of Anesthesia in Newborn Mice and Humans

“…The recorded network activity had a highly fragmented structure (defined as discontinuous activity) in all investigated areas (PFC, HP, LEC and OB). The full signal (i.e., entire LFP trace) consisted of transient episodes of oscillatory discharges with mixed frequencies (from here referred to as “active periods”), alternating with periods of relative electrical silence and suppressed activity (from here referred to as “silent periods”; Figure 1A; Khazipov et al, 2004; Hanganu et al, 2006; Brockmann et al, 2011; Bitzenhofer et al, 2017; Gretenkord et al, 2019). The prevalence of active periods decreased rapidly and robustly over time in all investigated brain areas upon urethane injection (Figure 1B).…”

“…Simultaneous recordings of HP and PFC, as well as OB and LEC were analyzed to assess the effects of anesthesia on long-range functional coupling. We previously showed that at the end of the first postnatal week hippocampal theta bursts drive the oscillatory entrainment of local circuits in the PFC, whereas discontinuous activity in OB controls the network activity in LEC (Brockmann et al, 2011; Ahlbeck et al, 2018; Gretenkord et al, 2019). Urethane did not modify these interactions.…”

ATP activation of peritubular cells drives testicular sperm transport

“…For testicular tissue clearing we adopted the CLARITY method ( Chung et al, 2013 ) with minor modifications ( Gretenkord et al, 2019 ). Briefly, testes from adult mice were fixed overnight at 4°C in hydrogel fixation solution containing 4% acrylamide, 0.05% bis-acrylamide, 0.25% VA-044 Initiator, 4% PFA in PBS -/- to maintain structural integrity.…”

Ongoing habenular activity is driven by forebrain networks and modulated by olfactory stimuli

“…While the precise definition of a 'brain state' can vary depending on the time scales of investigated phenomena, the link between ongoing (or spontaneous) brain activity and the current state of the brain is well accepted [8][9][10][11][12][13][14]. In fact, ongoing neural activity has been observed across the nervous system, from brain areas involved in sensory processing [15][16][17][18][19][20][21][22][23], to innate behaviors [24][25][26], and higher cognitive function [27][28][29][30][31][32][33][34][35][36][37]. Despite the presence of ongoing activity across the brain and its rapid alterations coupled with brain state transitions, dedicated neural pathways and their connection to ongoing brain activity and sensoryevoked transitions remain to be identified.…”