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Distinct roles of basal forebrain cholinergic neurons in spatial and object recognition memory.

Okada K, Nishizawa K, Kobayashi T, Sakata S, Kobayashi K - Sci Rep (2015)

Bottom Line: Eliminating MS/vDB neurons impairs spatial but not object recognition memory in the reference and working memory tasks, whereas NBM elimination undermines only object recognition memory in the working memory task.These impairments are restored by treatment with acetylcholinesterase inhibitors, anti-dementia drugs for AD.Our results highlight that MS/vDB and NBM cholinergic neurons are not only implicated in recognition memory but also have essential roles in different types of recognition memory.

View Article: PubMed Central - PubMed

Affiliation: Department of Behavioural Sciences, Graduate School of Integrated Arts &Sciences, Hiroshima University, Higashi-Hiroshima 739-8521, Japan.

ABSTRACT
Recognition memory requires processing of various types of information such as objects and locations. Impairment in recognition memory is a prominent feature of amnesia and a symptom of Alzheimer's disease (AD). Basal forebrain cholinergic neurons contain two major groups, one localized in the medial septum (MS)/vertical diagonal band of Broca (vDB), and the other in the nucleus basalis magnocellularis (NBM). The roles of these cell groups in recognition memory have been debated, and it remains unclear how they contribute to it. We use a genetic cell targeting technique to selectively eliminate cholinergic cell groups and then test spatial and object recognition memory through different behavioural tasks. Eliminating MS/vDB neurons impairs spatial but not object recognition memory in the reference and working memory tasks, whereas NBM elimination undermines only object recognition memory in the working memory task. These impairments are restored by treatment with acetylcholinesterase inhibitors, anti-dementia drugs for AD. Our results highlight that MS/vDB and NBM cholinergic neurons are not only implicated in recognition memory but also have essential roles in different types of recognition memory.

No MeSH data available.


Related in: MedlinePlus

Drug recovery of spatial reference memory deficit in mice lacking MS/vDB cholinergic neurons.(a) Experimental design for recovery of memory deficit. Mice were injected with IT solution into the MS/vDB, administered i.p. with saline or Done/Riva (2 and 4 μmol/kg), and tested for spatial reference memory with the serial object exploration task. Two cholinergic systems are schematically illustrated in in sections modified from the Allen Mouse Brain Atlas (http://mouse.brain-map.org/)53. (b) Mean number of contacts with the non-displaced and displaced objects on a per-object basis in the spatial recognition test. Data are presented as mean ± s.e.m. n = 8 for each group. *P < 0.05 vs non-displaced object (Bonferroni method). NS, not significant.
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f4: Drug recovery of spatial reference memory deficit in mice lacking MS/vDB cholinergic neurons.(a) Experimental design for recovery of memory deficit. Mice were injected with IT solution into the MS/vDB, administered i.p. with saline or Done/Riva (2 and 4 μmol/kg), and tested for spatial reference memory with the serial object exploration task. Two cholinergic systems are schematically illustrated in in sections modified from the Allen Mouse Brain Atlas (http://mouse.brain-map.org/)53. (b) Mean number of contacts with the non-displaced and displaced objects on a per-object basis in the spatial recognition test. Data are presented as mean ± s.e.m. n = 8 for each group. *P < 0.05 vs non-displaced object (Bonferroni method). NS, not significant.

Mentions: First, we tested the recovery of the deficit in spatial reference memory in the mice lacking the MS/vDB cholinergic neurons. The Tg and non-Tg mice were given the IT solution bilaterally into the MS/vDB, administered saline or different doses of Done and Riva (2 and 4 μmol/kg) intraperitoneally (i.p.), and then used for the serial object exploration task (Fig. 4a). In the spatial reference memory test, the number of contacts with the displaced objects was significantly increased compared to that with the non-displaced objects in the Tg mice that received high/low doses of Done and high dose of Riva (Fig. 4b; group: F9,70 = 0.720, P = 0.689; objects: F1,70 = 78.917, P < 0.001; interaction: F9,70 = 2.256, P = 0.028; two-way ANOVA; P < 0.05), although the contact number for the two objects was not altered in the Tg mice that were administered saline. In the non-Tg mice, the number for the displaced objects was significantly higher than for the non-displaced objects in all mouse groups (P < 0.05). These data show that the deficit in spatial reference memory in mice lacking the MS/vDB cholinergic neurons can be recovered by the treatment with AChE inhibitors.


Distinct roles of basal forebrain cholinergic neurons in spatial and object recognition memory.

Okada K, Nishizawa K, Kobayashi T, Sakata S, Kobayashi K - Sci Rep (2015)

Drug recovery of spatial reference memory deficit in mice lacking MS/vDB cholinergic neurons.(a) Experimental design for recovery of memory deficit. Mice were injected with IT solution into the MS/vDB, administered i.p. with saline or Done/Riva (2 and 4 μmol/kg), and tested for spatial reference memory with the serial object exploration task. Two cholinergic systems are schematically illustrated in in sections modified from the Allen Mouse Brain Atlas (http://mouse.brain-map.org/)53. (b) Mean number of contacts with the non-displaced and displaced objects on a per-object basis in the spatial recognition test. Data are presented as mean ± s.e.m. n = 8 for each group. *P < 0.05 vs non-displaced object (Bonferroni method). NS, not significant.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4526880&req=5

f4: Drug recovery of spatial reference memory deficit in mice lacking MS/vDB cholinergic neurons.(a) Experimental design for recovery of memory deficit. Mice were injected with IT solution into the MS/vDB, administered i.p. with saline or Done/Riva (2 and 4 μmol/kg), and tested for spatial reference memory with the serial object exploration task. Two cholinergic systems are schematically illustrated in in sections modified from the Allen Mouse Brain Atlas (http://mouse.brain-map.org/)53. (b) Mean number of contacts with the non-displaced and displaced objects on a per-object basis in the spatial recognition test. Data are presented as mean ± s.e.m. n = 8 for each group. *P < 0.05 vs non-displaced object (Bonferroni method). NS, not significant.
Mentions: First, we tested the recovery of the deficit in spatial reference memory in the mice lacking the MS/vDB cholinergic neurons. The Tg and non-Tg mice were given the IT solution bilaterally into the MS/vDB, administered saline or different doses of Done and Riva (2 and 4 μmol/kg) intraperitoneally (i.p.), and then used for the serial object exploration task (Fig. 4a). In the spatial reference memory test, the number of contacts with the displaced objects was significantly increased compared to that with the non-displaced objects in the Tg mice that received high/low doses of Done and high dose of Riva (Fig. 4b; group: F9,70 = 0.720, P = 0.689; objects: F1,70 = 78.917, P < 0.001; interaction: F9,70 = 2.256, P = 0.028; two-way ANOVA; P < 0.05), although the contact number for the two objects was not altered in the Tg mice that were administered saline. In the non-Tg mice, the number for the displaced objects was significantly higher than for the non-displaced objects in all mouse groups (P < 0.05). These data show that the deficit in spatial reference memory in mice lacking the MS/vDB cholinergic neurons can be recovered by the treatment with AChE inhibitors.

Bottom Line: Eliminating MS/vDB neurons impairs spatial but not object recognition memory in the reference and working memory tasks, whereas NBM elimination undermines only object recognition memory in the working memory task.These impairments are restored by treatment with acetylcholinesterase inhibitors, anti-dementia drugs for AD.Our results highlight that MS/vDB and NBM cholinergic neurons are not only implicated in recognition memory but also have essential roles in different types of recognition memory.

View Article: PubMed Central - PubMed

Affiliation: Department of Behavioural Sciences, Graduate School of Integrated Arts &Sciences, Hiroshima University, Higashi-Hiroshima 739-8521, Japan.

ABSTRACT
Recognition memory requires processing of various types of information such as objects and locations. Impairment in recognition memory is a prominent feature of amnesia and a symptom of Alzheimer's disease (AD). Basal forebrain cholinergic neurons contain two major groups, one localized in the medial septum (MS)/vertical diagonal band of Broca (vDB), and the other in the nucleus basalis magnocellularis (NBM). The roles of these cell groups in recognition memory have been debated, and it remains unclear how they contribute to it. We use a genetic cell targeting technique to selectively eliminate cholinergic cell groups and then test spatial and object recognition memory through different behavioural tasks. Eliminating MS/vDB neurons impairs spatial but not object recognition memory in the reference and working memory tasks, whereas NBM elimination undermines only object recognition memory in the working memory task. These impairments are restored by treatment with acetylcholinesterase inhibitors, anti-dementia drugs for AD. Our results highlight that MS/vDB and NBM cholinergic neurons are not only implicated in recognition memory but also have essential roles in different types of recognition memory.

No MeSH data available.


Related in: MedlinePlus