Basal Forebrain Nuclei Display Distinct Projecting Pathways and Functional Circuits to Sensory Primary and Prefrontal Cortices in the Rat

Abstract

Recent evidence supports that specific projections between different basal forebrain (BF) nuclei and their cortical targets are necessary to modulate cognitive functions in the cortex. We tested the hypothesis of the existence of specific neuronal populations in the BF linking with specific sensory, motor, and prefrontal cortices in rats. Neuronal tracing techniques were performed using retrograde tracers injected in the primary somatosensory (S1), auditory (A1), and visual (V1) cortical areas, in the medial prefrontal cortex (mPFC) as well as in BF nuclei. Results indicate that the vertical and horizontal diagonal band of Broca (VDB/HDB) nuclei target specific sensory cortical areas and maintains reciprocal projections with the prelimbic/infralimbic (PL/IL) area of the mPFC. The basal magnocellular nucleus (B nucleus) has more widespread targets in the sensory-motor cortex and does not project to the PL/IL cortex. Optogenetic stimulation was used to establish if BF neurons modulate whisker responses recorded in S1 and PL/IL cortices. We drove the expression of high levels of channelrhodopsin-2, tagged with a fluorescent protein (ChR2-eYFP) by injection of a virus in HDB or B nuclei. Blue-light pulses were delivered to the BF through a thin optic fiber to stimulate these neurons. Blue-light stimulation directed toward the HDB facilitated whisker responses in S1 cortex through activation of muscarinic receptors. The same optogenetic stimulation of HDB induced an inhibition of whisker responses in mPFC by activation of nicotinic receptors. Blue-light stimulation directed toward the B nucleus had lower effects than HDB stimulation. Our findings pointed the presence of specific neuronal networks between the BF and the cortex that may play different roles in the control of cortical activity.

Input dependent modulation of olfactory bulb activity by HDB GABAergic projections

“…The distinct early sensory modulation effects of cholinergic and GABAergic BF neurons observed in this study might therefore be owed to the different functions of these two basal forebrain systems. Here we targeted cholinergic and GABAergic projections neurons located primarily in the same area (HDB) since previous publications have shown that populations from different basal forebrain centers can have heterogeneous effects 81 . However, we cannot exclude that the effects observed during GABAergic fiber stimulation were, at least partially, derived from GABAergic fibers originating in the MCPO, a nucleus containing a majority of GABAergic bulbopetal neurons 23,25,47,115 .…”

“…The basal forebrain is critical for many cognitive processes [65][66][67][68][69] as well as for sensory information processing 51,[70][71][72][73][74][75] . Despite longstanding knowledge about the heterogeneity of BF derived long-range projections 17,25,76,77 , studies examining their function in sensory processing so far have been focused almost exclusively on cholinergic projections 3,27,28,46,[78][79][80][81][82] .…”

Cholinergic Modulation of the Default Mode Like Network in Rats

“…Viral vectors containing inverted DNA constructs encoding DREADDs were stereotactically injected in the right BFB ( Figure 1 ). Since cholinergic neurons in the anterior medial portion of the BFB have been shown to project to the medial and frontal cortex, and have been implicated to play a role in attention, these medial nuclei were targeted during the stereotactic surgery ( Ballinger et al., 2016 ; Chaves-Coira et al., 2018 ). Immunohistochemical experiments were performed on eight animals to validate transfection of cholinergic neurons in the target region.…”

Carbachol and Nicotine in Prefrontal Cortex Have Differential Effects on Sleep-Wake States

“…The prefrontal cortex receives cholinergic innervation from basal forebrain and laterodorsal/pedunculopontine tegmentum (Saper and Loewy, 1982;Vincent et al, 1983;Satoh and Fibiger, 1986;Chaves-Coira et al, 2018), both of which have wake-active and REM sleep-active neurons (Lee et al, 2005;Sakai, 2012;Boucetta et al, 2014). Although the role of prefrontal ACh from either of these sources in triggering the onset of wake state is not clear, recent optogenetic studies showed that the stimulation of basal forebrain cholinergic neurons induced wakefulness (Irmak and de Lecea, 2014;Xu et al, 2015) whereas the stimulation of PPT cholinergic neurons primarily increased REM sleep (Van Dort et al, 2015).…”