Cell type specific tracing of the subcortical input to primary visual cortex from the basal forebrain

Abstract

The basal forebrain provides cholinergic inputs to primary visual cortex (V1) that play a key modulatory role on visual function. While basal forebrain afferents terminate in the infragranular layers of V1, acetylcholine is delivered to more superficial layers through volume transmission. Nevertheless, direct synaptic contact in deep layers 5 and 6 may provide a more immediate effect on V1 modulation. Using helper viruses with cell type specific promoters to target retrograde infection of pseudotyped and genetically modified rabies virus evidence was found for direct synaptic input onto V1 inhibitory neurons. These inputs were similar in number to geniculocortical inputs and, therefore, considered robust. In contrast, while clear evidence for dorsal lateral geniculate nucleus input to V1 excitatory neurons was found, there was no evidence of direct synaptic input from the basal forebrain. These results suggest a direct and more immediate influence of the basal forebrain on local V1 inhibition.

Forebrain Cholinergic Signaling: Wired and Phasic, Not Tonic, and Causing Behavior

“…Anatomical studies in rodents have revealed the presence of Ͼ30 morphologically defined cell clusters in basal forebrain as well as precise relationships between the afferent and efferent projection patterns of individual cholinergic cell groups. Likewise, in humans, postmortem cytoarchitectonic studies of the basal forebrain, and functional imaging studies analyzing functional connectivity between basal forebrain subregions and cortical regions, have begun to demonstrate that cellular subdivisions in the basal forebrain give rise to topographically organized, segregated projections to specific target regions (Zaborszky et al, 2008(Zaborszky et al, , 2015aGielow and Zaborszky, 2017;Huppé-Gourgues et al, 2018;Lean et al, 2019). Combined with anatomical evidence indicating limited axonal collateralization (Price and Stern, 1983), this work suggests that cholinergic neurons can have regionally discrete effects, which, for example, may impact information processing in individual cortical areas and layers (Tingley et al, 2015;e.g., Chavez and Zaborszky, 2017).…”

Forebrain Cholinergic Signaling: Wired and Phasic, not Tonic, and Causing Behavior

“…Contemporary neuroanatomical research has revealed a heretofore unexpected degree of anatomical and functional parcellation of basal forebrain cholinergic neurons and a highly topographical organization of the basal forebrain cholinergic projection system, including complex relationships between basal forebrain afferent with efferent projection patterns (Zaborszky et al, 2008;Zaborszky et al, 2015b;Zaborszky et al, 2015a;Gielow and Zaborszky, 2017;Huppé-Gourgues et al, 2018;Lean et al, 2019). Combined with a limited degree of axonal collateralization (Price and Stern, 1983), this evidence suggests a neuronal projection system that can support regionally discrete cholinergic stimulation (see also Chavez and Zaborszky, 2017).…”

“…These hallmarks include the presence of a relatively small number of soma in the basal forebrain giving rise to a relatively large innervation space, a limited topographical organization of cholinergic projections, a substantial degree of axonal collateralization, and the presence of extrasynaptic, or non-classical, receptors and, by implication, volume-transmission. Consequently, theories of cholinergic function have centered around the functions of slowly changing extracellular ACh levels (Yu and Dayan, 2002) and the role of volume transmission in, for example, primary visual cortex function (e.g., Lean et al, 2019). The main goal of this article is to critically probe these traditional descriptions, including our own prior interpretations (e.g., St Peters et al, 2011), that ACh acts by slowly (over 100 of seconds or even minutes) affecting the excitability of widespread target regions, and thereby primarily modulating relatively global functions such as "arousal".…”

Novel rabies virus variant for bi-directional optical control reveals modulatory influence of the pulvinar on visual cortex in rat

“…In addition, a major benefit of using rabies virus to package channelrhodopsin genes is the ability to pseudotype the virus (Wickersham et al 2007b) to target specific protein receptors delivered transgenically, via helper viruses, and through single cell electroporation (Marshel et al 2010;Wall et al 2010;Miyamichi et al 2011;Rancz et al 2011;Kim et al 2015;Callaway and Luo, 2015;Wertz et al 2015;Wall et al, 2016). For example, recently we developed a suite of helper viruses designed to transduce avian tumor virus receptor A (TVA) and oG to excitatory (LV-αCamKII) or inhibitory (AAV-GAD1) subpopulations (Liu et al, 2013;Lean et al, 2019).…”