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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 restoration of spatial and object working memory defects in mice lacking MS/vDB or NBM cholinergic neurons.(a) Experimental design for restoration of memory defects. Mice were injected with IT solution into the MS/vDB or NBM, administered i.p. with saline or Done/Riva (2 and 4 μmol/kg), and tested for spatial and object working memory with the one-trial object exploration task. The 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 with 3- or 30-min delay period. The mice injected with IT solution into the MS/vDB were used. 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. (c) Mean number of contacts with the non-displaced and novel objects on a per-object basis in the object recognition test with 3- or 30-min delay period. The mice injected with IT solution into the NBM were used. Data are presented as mean ± s.e.m. n = 8–12 for each group. *P < 0.05 vs non-displaced object (Bonferroni method). NS, not significant.
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f5: Drug restoration of spatial and object working memory defects in mice lacking MS/vDB or NBM cholinergic neurons.(a) Experimental design for restoration of memory defects. Mice were injected with IT solution into the MS/vDB or NBM, administered i.p. with saline or Done/Riva (2 and 4 μmol/kg), and tested for spatial and object working memory with the one-trial object exploration task. The 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 with 3- or 30-min delay period. The mice injected with IT solution into the MS/vDB were used. 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. (c) Mean number of contacts with the non-displaced and novel objects on a per-object basis in the object recognition test with 3- or 30-min delay period. The mice injected with IT solution into the NBM were used. Data are presented as mean ± s.e.m. n = 8–12 for each group. *P < 0.05 vs non-displaced object (Bonferroni method). NS, not significant.

Mentions: Next, the mice were given IT solution bilaterally into the MS/vDB or NBM, treated with different doses of Done and Riva (2 and 4 μmol/kg i.p.), and then tested in the one-trial object exploration task (Fig. 5a). The mice with the injections into the MS/vDB and NBM were used for the tests of spatial and object working memory, respectively. In the spatial working memory test, the number of contacts with the displaced objects was higher compared to that with the non-displaced objects in the Tg mice that received high/low doses of Done and Riva (Fig. 5b; group: F9,70 = 4.274, P < 0.001; objects: F1,70 = 102.318, P < 0.001; interaction: F9,70 = 2.879, P = 0.006 for 3 min; group: F9,70 = 3.361, P = 0.002; objects: F1,70 = 134.641, P < 0.001; interaction: F9,70 = 3.174, P = 0.003 for 30 min; two-way ANOVA, P < 0.05), although the contacts with the two objects did not differ in the saline-treated Tg mice. In the non-Tg mice, the number for the displaced objects was significantly larger than for the non-displaced objects in all mouse groups (P < 0.05). In the object working memory test, the contacts with the novel objects showed an increment compared to those with the non-displaced objects in the Tg mice that received high/low doses of Done and Riva (Fig. 5c; group: F9,88 = 1.701, P = 0.101; objects: F1,88 = 105.810, P < 0.001; interaction: F9,88 = 2.104, P = 0.037 for 3 min; group: F9,88 = 2.267, P = 0.025; objects: F1,88 = 88.605, P < 0.001; interaction: F9,88 = 2.681, P = 0.008 for 30 min; two-way ANOVA, P < 0.05), though the contacts with the two objects were indistinguishable in the saline-treated Tg mice. In the non-Tg mice, the number for the novel objects was higher than for the non-displaced objects in all groups (P < 0.05). These data demonstrate the restoration of spatial and object working memory defects in mice lacking the MS/vDB and NBM cholinergic neurons through 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 restoration of spatial and object working memory defects in mice lacking MS/vDB or NBM cholinergic neurons.(a) Experimental design for restoration of memory defects. Mice were injected with IT solution into the MS/vDB or NBM, administered i.p. with saline or Done/Riva (2 and 4 μmol/kg), and tested for spatial and object working memory with the one-trial object exploration task. The 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 with 3- or 30-min delay period. The mice injected with IT solution into the MS/vDB were used. 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. (c) Mean number of contacts with the non-displaced and novel objects on a per-object basis in the object recognition test with 3- or 30-min delay period. The mice injected with IT solution into the NBM were used. Data are presented as mean ± s.e.m. n = 8–12 for each group. *P < 0.05 vs non-displaced object (Bonferroni method). NS, not significant.
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f5: Drug restoration of spatial and object working memory defects in mice lacking MS/vDB or NBM cholinergic neurons.(a) Experimental design for restoration of memory defects. Mice were injected with IT solution into the MS/vDB or NBM, administered i.p. with saline or Done/Riva (2 and 4 μmol/kg), and tested for spatial and object working memory with the one-trial object exploration task. The 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 with 3- or 30-min delay period. The mice injected with IT solution into the MS/vDB were used. 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. (c) Mean number of contacts with the non-displaced and novel objects on a per-object basis in the object recognition test with 3- or 30-min delay period. The mice injected with IT solution into the NBM were used. Data are presented as mean ± s.e.m. n = 8–12 for each group. *P < 0.05 vs non-displaced object (Bonferroni method). NS, not significant.
Mentions: Next, the mice were given IT solution bilaterally into the MS/vDB or NBM, treated with different doses of Done and Riva (2 and 4 μmol/kg i.p.), and then tested in the one-trial object exploration task (Fig. 5a). The mice with the injections into the MS/vDB and NBM were used for the tests of spatial and object working memory, respectively. In the spatial working memory test, the number of contacts with the displaced objects was higher compared to that with the non-displaced objects in the Tg mice that received high/low doses of Done and Riva (Fig. 5b; group: F9,70 = 4.274, P < 0.001; objects: F1,70 = 102.318, P < 0.001; interaction: F9,70 = 2.879, P = 0.006 for 3 min; group: F9,70 = 3.361, P = 0.002; objects: F1,70 = 134.641, P < 0.001; interaction: F9,70 = 3.174, P = 0.003 for 30 min; two-way ANOVA, P < 0.05), although the contacts with the two objects did not differ in the saline-treated Tg mice. In the non-Tg mice, the number for the displaced objects was significantly larger than for the non-displaced objects in all mouse groups (P < 0.05). In the object working memory test, the contacts with the novel objects showed an increment compared to those with the non-displaced objects in the Tg mice that received high/low doses of Done and Riva (Fig. 5c; group: F9,88 = 1.701, P = 0.101; objects: F1,88 = 105.810, P < 0.001; interaction: F9,88 = 2.104, P = 0.037 for 3 min; group: F9,88 = 2.267, P = 0.025; objects: F1,88 = 88.605, P < 0.001; interaction: F9,88 = 2.681, P = 0.008 for 30 min; two-way ANOVA, P < 0.05), though the contacts with the two objects were indistinguishable in the saline-treated Tg mice. In the non-Tg mice, the number for the novel objects was higher than for the non-displaced objects in all groups (P < 0.05). These data demonstrate the restoration of spatial and object working memory defects in mice lacking the MS/vDB and NBM cholinergic neurons through 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