title: Modulatory compartments in cortex and local regulation of cholinergic tone.
abstract: Neuromodulatory signaling is generally considered broad in its impact across cortex. However, variations in the characteristics of cortical circuits may introduce regionally-specific responses to diffuse modulatory signals. Features such as patterns of axonal innervation, tissue tortuosity and molecular diffusion, effectiveness of degradation pathways, subcellular receptor localization, and patterns of receptor expression can lead to local modification of modulatory inputs. We propose that modulatory compartments exist in cortex and can be defined by variation in structural features of local circuits. Further, we argue that these compartments are responsible for local regulation of neuromodulatory tone. For the cholinergic system, these modulatory compartments are regions of cortical tissue within which signaling conditions for acetylcholine are relatively uniform, but between which signaling can vary profoundly. In the visual system, evidence for the existence of compartments indicates that cholinergic modulation likely differs across the visual pathway. We argue that the existence of these compartments calls for thinking about cholinergic modulation in terms of finer-grained control of local cortical circuits than is implied by the traditional view of this system as a diffuse modulator. Further, an understanding of modulatory compartments provides an opportunity to better understand and perhaps correct signal modifications that lead to pathological states.
authors.affiliation: Department of Psychology, Vanderbilt University, PMB 407817, 2301 Vanderbilt Place, Nashville, TN 37240-7817, USA. Electronic address: jennifer.j.coppola@vanderbilt.edu.
authors.forename: Jennifer J
authors.initials: JJ
authors.lastname: Coppola
authors.affiliation: Department of Psychology, Vanderbilt University, PMB 407817, 2301 Vanderbilt Place, Nashville, TN 37240-7817, USA. Electronic address: nicholas.j.ward@vanderbilt.edu.
authors.forename: Nicholas J
authors.initials: NJ
authors.lastname: Ward
authors.affiliation: Computational Neurobiology Laboratory, Salk Institute for Biological Studies, 10610 North Torrey Pines Road, La Jolla, CA 92093, USA. Electronic address: jadi@salk.edu.
authors.forename: Monika P
authors.initials: MP
authors.lastname: Jadi
authors.affiliation: Department of Psychology, Vanderbilt University, PMB 407817, 2301 Vanderbilt Place, Nashville, TN 37240-7817, USA. Electronic address: anita.disney@vanderbilt.edu.
authors.forename: Anita A
authors.initials: AA
authors.lastname: Disney
mesh_terms: D000109:Acetylcholine / Q000378:metabolism*; D002540:Cerebral Cortex / Q000502:physiology*; D006801:Humans; D011950:Receptors, Cholinergic / Q000378:metabolism; D014795:Visual Pathways / Q000502:physiology*
chemical_list: D011950:Receptors, Cholinergic; D000109:Acetylcholine
keywords: Acetylcholine; Compartments; Cortex; Neuromodulation; Volume transmission