Cholinergic Inputs from Basal Forebrain Add an Excitatory Bias to Odor Coding in the Olfactory Bulb

Abstract

Cholinergic modulation of central circuits is associated with active sensation, attention, and learning, yet the neural circuits and temporal dynamics underlying cholinergic effects on sensory processing remain unclear. Understanding the effects of cholinergic modulation on particular circuits is complicated by the widespread projections of cholinergic neurons to telencephalic structures that themselves are highly interconnected. Here we examined how cholinergic projections from basal forebrain to the olfactory bulb (OB) modulate output from the first stage of sensory processing in the mouse olfactory system. By optogenetically activating their axons directly in the OB, we found that cholinergic projections from basal forebrain regulate OB output by increasing the spike output of presumptive mitral/tufted cells. Cholinergic stimulation increased mitral/tufted cell spiking in the absence of inhalation-driven sensory input and further increased spiking responses to inhalation of odorless air and to odorants. This modulation was rapid and transient, was dependent on local cholinergic signaling in the OB, and differed from modulation by optogenetic activation of cholinergic neurons in basal forebrain, which led to a mixture of mitral/tufted cell excitation and suppression. Finally, bulbar cholinergic enhancement of mitral/tufted cell odorant responses was robust and occurred independent of the strength or even polarity of the odorant-evoked response, indicating that cholinergic modulation adds an excitatory bias to mitral/tufted cells as opposed to increasing response gain or sharpening response spectra. These results are consistent with a role for the basal forebrain cholinergic system in dynamically regulating the sensitivity to or salience of odors during active sensing of the olfactory environment.

Diverse Representations of Olfactory Information in Centrifugal Feedback Projections

“…Instead, feedback projections are organizationally distinct. As a result, any putative maps in the olfactory system, be they the ones that originate from the AON and the piriform cortex as we have studied, or projections more generally for diverse areas such as neuromodulatory centers (Rothermel et al, 2014), may be as much about the behaviorally relevant outputs in response to odors as they are about the chemical structure of those odors.…”

An integrative role for the superior colliculus in selecting targets for movements

“…One possibility, however, is that cholinergic input to the SC serves to modulate the competition between circuits representing targets for movement, similar to how other brain stem sources of cholinergic input modulate sensory representations in target structures (Castro-Alamancos 2004;Froemke et al 2007;Goard and Dan 2009;Kilgard and Merzenich 1998;Ma and Luo 2012;Rothermel et al 2014). Indeed, cholinergic input to brain stem nuclei has been proposed to modulate motor-related functions, including locomotor activity (Steckler et al 1994) and muscle control (Kelland and Asdourian 1989).…”

Construction of functional neuronal circuitry in the olfactory bulb

“…The OB receives massive inputs from the horizontal limb of the diagonal band of Broca (HDB) of the basal forebrain where cholinergic neurons reside [95]. Odor response tuning of mitral/tufted cells are sharpened by cholinergic inputs at multiple levels, facilitating contrast enhancement [96][97][98]. GABAergic neurons in HDB, which directly inhibit granule cells, are also important for olfactory discrimination [99].…”