Substitution of natural sensory input by artificial neurostimulation of an amputated trigeminal nerve does not prevent the degeneration of basal forebrain cholinergic circuits projecting to the somatosensory cortex.

Celia Herrera-Rincon,Fivos Panetsos

doi:10.3389/fncel.2014.00385

Abstract

Peripheral deafferentation downregulates acetylcholine (ACh) synthesis in sensory cortices. However, the responsible neural circuits and processes are not known. We irreversibly transected the rat infraorbital nerve and implanted neuroprosthetic microdevices for proximal stump stimulation, and assessed cytochrome-oxidase and choline- acetyl-transferase (ChAT) in somatosensory, auditory and visual cortices; estimated the number and density of ACh-neurons in the magnocellular basal nucleus (MBN); and localized down-regulated ACh-neurons in basal forebrain using retrograde labeling from deafferented cortices. Here we show that nerve transection, causes down regulation of MBN cholinergic neurons. Stimulation of the cut nerve reverses the metabolic decline but does not affect the decrease in cholinergic fibers in cortex or cholinergic neurons in basal forebrain. Artifical stimulation of the nerve also has no affect of ACh-innervation of other cortices. Cortical ChAT depletion is due to loss of corticopetal MBN ChAT-expressing neurons. MBN ChAT downregulation is not due to a decrease of afferent activity or to a failure of trophic support. Basalocortical ACh circuits are sensory specific, ACh is provided to each sensory cortex “on demand” by dedicated circuits. Our data support the existence of a modality-specific cortex-MBN-cortex circuit for cognitive information processing.

Highlights

As early as the 1970s it has been known that sensory deafferentation provokes changes in the somatotopic maps at any relay station of the somatosensory pathway (Kaas, 1991)
DOWN-REGULATION OF CORTICAL ACETYLCHOLINE AND DROP OF CORTICOPETAL CHOLINERGIC NEURONS IN THE BASAL FOREBRAIN Our results show that downregulation of choline- acetyl-transferase (ChAT)-positive neuropil in the deafferented somatosensory cortex (Figures 4A-left,B, red www.frontiersin.org symbols) is correlated to ChAT downregulation in magnocellular basal nucleus (MBN) areas (Figures 5A-middle,B) which provide cholinergic innervation to the sensory-deprived cortex (Figure 6)
PERSPECTIVES Taken together, here we have shown that cortically projecting MBN neurons provide topographically specific, functionally independent inputs that are modality specific

Summary

Introduction

As early as the 1970s it has been known that sensory deafferentation provokes changes in the somatotopic maps at any relay station of the somatosensory pathway (Kaas, 1991). Sensory deprivation resulted in a clear decrease of the electrophysiological responses, metabolic activity, volume of the active neural tissue, and number of Parvalbuminand Calbindin-positive GABA-ergic neurons, all of them consistent with previous literature (Land and Simons, 1985; Diamond et al, 1994; Glazewski et al, 1998; Huang et al, 1998; Kelly et al, 1999; Machin et al, 2004; for review, see Fox, 2002) All these physiological alterations, both functional and metabolic, were prevented or significantly diminished when the peripheral nerve was chronically stimulated after the transection (Herrera-Rincon et al, 2012)

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