Cholinergic and GABAergic neuromodulatory basal forebrain projections differentially influence early sensory circuits in the mouse olfactory bulb

• Differenzielle Beeinflussung der frühen sensorischen Schaltkreise im olfaktorischen Bulbus der Maus durch cholinerge und GABAerge neuromodulatorische basale Vorderhirn-Projektionen

Böhm, Erik; Rothermel, Markus (Thesis advisor); Kampa, Björn M. (Thesis advisor)

Aachen : RWTH Aachen University (2020, 2021)
Dissertation / PhD Thesis

Dissertation, RWTH Aachen University, 2020

Abstract

Sensory filter mechanisms are crucial to isolate relevant information from a surrounding charged with an overwhelming amount of sensory stimuli. These vital processes are partly attentional-driven and, if disrupted, can lead to attention deficit hyperactivity and autism spectrum disorder. However, sensory filter mechanisms has not yet been completely understood. In this dissertation, we investigated the impact of the basal forebrain (BF) on olfactory sensory processing. The BF is a neuromodulatory center with multiple output pathways, which plays an important role by regulating attention. Mainly originating from a BF subregion, the so-called horizontal band of broca (HDB), cholinergic and GABAergic projection neurons innervate the olfactory bulb (OB). Although the cholinergic BF system has been extensively examined, studies focusing on cholinergic BF modulation effects on bulbar output often resulted in controversial findings regarding modulation effects and their potential functions. In contrast, GABAergic BF modulation effects on olfactory processing have only been sparsely investigated with significant gaps in the knowledge exist regarding in vivo recordings with fast temporal resolution techniques. Here, we present a direct comparison of optogenetic modulation effects between cholinergic and GABAergic BF projection neurons on mitral and tufted cells (MTCs), the principal OB output neurons. We used a mouse line expressing Cre under control of the ChAT or Gad2 promoter. By locally injecting a Cre-dependent viral expression vector (either channelrhodopsin-2 (ChR2), halorhodopsin (HR) or archaerhodopsin (ARCH)) into the HDB, we selectively targeted cholinergic or GABAergic BF neurons. Using extracellular in vivo recordings in anesthetized mice, we could show that optogenetic stimulation of cholinergic BF OB fibers added an excitatory bias to MTC firing. This leads to the assumption that the cholinergic BF input to the OB act as a baseline control model and improves odor detectability. In contrast, optogenetic stimulation of GABAergic BF fibers in the OB predominantly decreased spontaneous MTC firing, while odor-evoked spiking was mainly enhanced. This bimodal effect could, theoretically, be attention-regulated. We assumed that, contrary to the classical view, GABAergic BF modulation might be an important factor in attentional-controlled filtering processes of sensory input, that are known to improve the discrimination of odors. To investigate under which behavioral condition the two different HDB subpopulations are active, we have adapted and established a multi tetrode array (MTA). In the first preliminary proof-of-concept experiments in passively trained mice, we could show odorant-evoked activity in HDB neurons, which supports the hypothesis of a bottom-up connection between the OB and the BF. In conclusion, we could show that the BF as an individual region modulates OB output differentially via its two subpopulations, which might lead to a dynamic modulation of sensory processing in response to different behavioral tasks.