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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.

Herrera-Rincon C, Panetsos F - Front Cell Neurosci (2014)

Bottom Line: 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.MBN ChAT downregulation is not due to a decrease of afferent activity or to a failure of trophic support.Our data support the existence of a modality-specific cortex-MBN-cortex circuit for cognitive information processing.

View Article: PubMed Central - PubMed

Affiliation: Neurocomputing and Neurorobotics Research Group, Universidad Complutense de Madrid Madrid, Spain ; Biomathematics Department, Faculty of Biology and Faculty of Optics, Universidad Complutense de Madrid Madrid, Spain ; Instituto de Investigación Sanitaria del Hospital Clínico San Carlos Madrid, Spain.

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.

No MeSH data available.


Related in: MedlinePlus

Metabolic activity and cholinergic innervation in the barrel somatosensory cortex after amputation and after artificial stimulation of the transected infraorbital nerve. (A) CyO-reacted and ChAT-immunostained sections are shown in upper and lower row, respectively. Ipsilateral or unaffected hemispheres are on left, contralateral or affected hemispheres are on right. Peripheral deafferentation causes a decrease in gross structure and metabolic and cholinergic states of the affected barrel cortices (Amputated-right). Artificial stimulation of the transected nerve protects the metabolic activity of the affected barrel cortices. It maintains similar CyO-levels between the two hemispheres but does not avoid the deafferentation-dependent degenerative effect on cholinergic innervation (Prosthetic-right). Ipsilateral cortices show significantly lower ChAT-staining levels than the contralateral ones. In ipsilateral hemispheres rostral is right; in contralateral hemispheres rostral is left and lateral is top. Scale bars = 200 μm in CyO; 50 μm in ChAT. (B) Graphic representations of mean OD percentage changes of the contralateral vs. ipsilateral hemispheres indicated as C/I (%). Metabolic activity (CyO, left) and cholinergic innervation (ChAT, right) values of the barrel cortices of control, amputated, and prosthetic animals (represented by blue, red, and green symbols, respectively) are given separately for cortical layers II/III and IV and the whole II-IV field. Values are expressed as mean ± s.e.m. Significant differences are indicated by an asterisk (ANOVA, *P < 0.05).
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Figure 4: Metabolic activity and cholinergic innervation in the barrel somatosensory cortex after amputation and after artificial stimulation of the transected infraorbital nerve. (A) CyO-reacted and ChAT-immunostained sections are shown in upper and lower row, respectively. Ipsilateral or unaffected hemispheres are on left, contralateral or affected hemispheres are on right. Peripheral deafferentation causes a decrease in gross structure and metabolic and cholinergic states of the affected barrel cortices (Amputated-right). Artificial stimulation of the transected nerve protects the metabolic activity of the affected barrel cortices. It maintains similar CyO-levels between the two hemispheres but does not avoid the deafferentation-dependent degenerative effect on cholinergic innervation (Prosthetic-right). Ipsilateral cortices show significantly lower ChAT-staining levels than the contralateral ones. In ipsilateral hemispheres rostral is right; in contralateral hemispheres rostral is left and lateral is top. Scale bars = 200 μm in CyO; 50 μm in ChAT. (B) Graphic representations of mean OD percentage changes of the contralateral vs. ipsilateral hemispheres indicated as C/I (%). Metabolic activity (CyO, left) and cholinergic innervation (ChAT, right) values of the barrel cortices of control, amputated, and prosthetic animals (represented by blue, red, and green symbols, respectively) are given separately for cortical layers II/III and IV and the whole II-IV field. Values are expressed as mean ± s.e.m. Significant differences are indicated by an asterisk (ANOVA, *P < 0.05).

Mentions: In control animals no significant inter-hemispheric differences were observed in CyO neither in ChAT staining (Figures 3A,C and Table 1A). In A-animals sensory deprivation resulted in a dramatic decrease of both CyO and ChAT expression in the deafferented barrel cortex. Inter-hemispheric comparisons of CyO-intensity show differences of −22 ± 5%, −15 ± 1%, and −18 ± 3% for layers II/III, layer IV, and the total PMBSF, respectively and of −17 ± 2%, −20 ± 4%, and −18 ± 3% for the cholinergic neuropil (Figures 4A,B-left and Table 1B).


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.

Herrera-Rincon C, Panetsos F - Front Cell Neurosci (2014)

Metabolic activity and cholinergic innervation in the barrel somatosensory cortex after amputation and after artificial stimulation of the transected infraorbital nerve. (A) CyO-reacted and ChAT-immunostained sections are shown in upper and lower row, respectively. Ipsilateral or unaffected hemispheres are on left, contralateral or affected hemispheres are on right. Peripheral deafferentation causes a decrease in gross structure and metabolic and cholinergic states of the affected barrel cortices (Amputated-right). Artificial stimulation of the transected nerve protects the metabolic activity of the affected barrel cortices. It maintains similar CyO-levels between the two hemispheres but does not avoid the deafferentation-dependent degenerative effect on cholinergic innervation (Prosthetic-right). Ipsilateral cortices show significantly lower ChAT-staining levels than the contralateral ones. In ipsilateral hemispheres rostral is right; in contralateral hemispheres rostral is left and lateral is top. Scale bars = 200 μm in CyO; 50 μm in ChAT. (B) Graphic representations of mean OD percentage changes of the contralateral vs. ipsilateral hemispheres indicated as C/I (%). Metabolic activity (CyO, left) and cholinergic innervation (ChAT, right) values of the barrel cortices of control, amputated, and prosthetic animals (represented by blue, red, and green symbols, respectively) are given separately for cortical layers II/III and IV and the whole II-IV field. Values are expressed as mean ± s.e.m. Significant differences are indicated by an asterisk (ANOVA, *P < 0.05).
© Copyright Policy - open-access
Related In: Results  -  Collection

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Figure 4: Metabolic activity and cholinergic innervation in the barrel somatosensory cortex after amputation and after artificial stimulation of the transected infraorbital nerve. (A) CyO-reacted and ChAT-immunostained sections are shown in upper and lower row, respectively. Ipsilateral or unaffected hemispheres are on left, contralateral or affected hemispheres are on right. Peripheral deafferentation causes a decrease in gross structure and metabolic and cholinergic states of the affected barrel cortices (Amputated-right). Artificial stimulation of the transected nerve protects the metabolic activity of the affected barrel cortices. It maintains similar CyO-levels between the two hemispheres but does not avoid the deafferentation-dependent degenerative effect on cholinergic innervation (Prosthetic-right). Ipsilateral cortices show significantly lower ChAT-staining levels than the contralateral ones. In ipsilateral hemispheres rostral is right; in contralateral hemispheres rostral is left and lateral is top. Scale bars = 200 μm in CyO; 50 μm in ChAT. (B) Graphic representations of mean OD percentage changes of the contralateral vs. ipsilateral hemispheres indicated as C/I (%). Metabolic activity (CyO, left) and cholinergic innervation (ChAT, right) values of the barrel cortices of control, amputated, and prosthetic animals (represented by blue, red, and green symbols, respectively) are given separately for cortical layers II/III and IV and the whole II-IV field. Values are expressed as mean ± s.e.m. Significant differences are indicated by an asterisk (ANOVA, *P < 0.05).
Mentions: In control animals no significant inter-hemispheric differences were observed in CyO neither in ChAT staining (Figures 3A,C and Table 1A). In A-animals sensory deprivation resulted in a dramatic decrease of both CyO and ChAT expression in the deafferented barrel cortex. Inter-hemispheric comparisons of CyO-intensity show differences of −22 ± 5%, −15 ± 1%, and −18 ± 3% for layers II/III, layer IV, and the total PMBSF, respectively and of −17 ± 2%, −20 ± 4%, and −18 ± 3% for the cholinergic neuropil (Figures 4A,B-left and Table 1B).

Bottom Line: 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.MBN ChAT downregulation is not due to a decrease of afferent activity or to a failure of trophic support.Our data support the existence of a modality-specific cortex-MBN-cortex circuit for cognitive information processing.

View Article: PubMed Central - PubMed

Affiliation: Neurocomputing and Neurorobotics Research Group, Universidad Complutense de Madrid Madrid, Spain ; Biomathematics Department, Faculty of Biology and Faculty of Optics, Universidad Complutense de Madrid Madrid, Spain ; Instituto de Investigación Sanitaria del Hospital Clínico San Carlos Madrid, Spain.

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.

No MeSH data available.


Related in: MedlinePlus