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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

Selective targeting of cholinergic cell groups in the basal forebrain.(a) Expression of IL-2Rα/mVenus products in the basal forebrain in the Tg mice revealed by immunostaining for mVenus with sections from the MS/vDB and NBM. Scale bars: 200 μm. The brain areas corresponding to light microscopic images are shown in sections modified from an atlas of the mouse brain (Allen Mouse Brain Atlas. Available from: http://mouse.brain-map.org/)53. (b) Cell type-specific expression of transgene products in cholinergic neurons in the MS, vDB, and NMB shown by double immunofluorescence histochemistry for mVenus and ChAT. In a merged image, green signals (mVenus) overlap with red signals (ChAT), thus emitting yellow signals. Scale bars: 200 μm. (c,d) Intracranial injection by using stereotaxic surgery into the MS/vDB (c) or NBM (d). Two cholinergic systems are schematically illustrated in the left panel and injection coordinates are indicated in the right panel in sections modified from the Allen Mouse Brain Atlas http://mouse.brain-map.org/)53. The anteroposterior coordinates (mm) from bregma are shown. Scale bars: 1 mm. (e,f) Immunohistochemical staining for ChAT with sections prepared from the mice 7 days after IT or PBS injection into the MS/vDB (e) or NBM (f). Scale bars: 1 mm. Lower panels show cell counts of ChAT-positive neurons. Data are presented as mean ± s.e.m. n = 5 for each group. *P < 0.05 vs each of other three groups (Bonferroni method). (g) Immunostaining for parvalbumin with sections through the MS/vDB and NBM prepared from the IT-injected mice into the MS/vDB or NBM. Scale bars: 1 mm. Right panel shows cell counts of parvalbumin-positive cells. Data are presented as mean ± s.e.m. n = 5 for each group. (h) AChE staining with sections through the hippocampus (HPC), perirhinal cortex (PRC), and medial prefrontal cortex (mPFC) prepared from the IT-injected mice into the MS/vDB or NBM. Scale bars: 200 μm.
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f1: Selective targeting of cholinergic cell groups in the basal forebrain.(a) Expression of IL-2Rα/mVenus products in the basal forebrain in the Tg mice revealed by immunostaining for mVenus with sections from the MS/vDB and NBM. Scale bars: 200 μm. The brain areas corresponding to light microscopic images are shown in sections modified from an atlas of the mouse brain (Allen Mouse Brain Atlas. Available from: http://mouse.brain-map.org/)53. (b) Cell type-specific expression of transgene products in cholinergic neurons in the MS, vDB, and NMB shown by double immunofluorescence histochemistry for mVenus and ChAT. In a merged image, green signals (mVenus) overlap with red signals (ChAT), thus emitting yellow signals. Scale bars: 200 μm. (c,d) Intracranial injection by using stereotaxic surgery into the MS/vDB (c) or NBM (d). Two cholinergic systems are schematically illustrated in the left panel and injection coordinates are indicated in the right panel in sections modified from the Allen Mouse Brain Atlas http://mouse.brain-map.org/)53. The anteroposterior coordinates (mm) from bregma are shown. Scale bars: 1 mm. (e,f) Immunohistochemical staining for ChAT with sections prepared from the mice 7 days after IT or PBS injection into the MS/vDB (e) or NBM (f). Scale bars: 1 mm. Lower panels show cell counts of ChAT-positive neurons. Data are presented as mean ± s.e.m. n = 5 for each group. *P < 0.05 vs each of other three groups (Bonferroni method). (g) Immunostaining for parvalbumin with sections through the MS/vDB and NBM prepared from the IT-injected mice into the MS/vDB or NBM. Scale bars: 1 mm. Right panel shows cell counts of parvalbumin-positive cells. Data are presented as mean ± s.e.m. n = 5 for each group. (h) AChE staining with sections through the hippocampus (HPC), perirhinal cortex (PRC), and medial prefrontal cortex (mPFC) prepared from the IT-injected mice into the MS/vDB or NBM. Scale bars: 200 μm.

Mentions: We performed the selective elimination of cholinergic neurons in the basal forebrain by using IT-mediated cell targeting2829. The recombinant IT used was anti-Tac(Fv)-PE38, which consists of single-chain variable regions of a monoclonal antibody for human interleukin-2 receptor α-subunit (IL-2Rα) fused to a bacterial exotoxin catalytic fragment. The transgene construct contained the gene cassette encoding human IL-2Rα fused to a variant of enhanced yellow fluorescent protein (mVenus) introduced into the initiation codon site of the gene encoding choline acetyltransferase (ChAT) in a bacterial artificial chromosome clone30 (see Supplementary Fig. S1). The microinjection technique was used to generate multiple independent Tg mouse founders, and one strain, termed ChAT-IL-2Rα/mVenus997-6, expressed the IL-2Rα/mVenus transgene in both the Ms/vDB and NBM regions (Fig. 1a). Double immunofluorescence histochemistry detected mVenus-positive signals in the majority of ChAT-positive neurons, and overlapping signal ratios were 93% and 98% in the MS/vDB and NBM, respectively (Fig. 1b).


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)

Selective targeting of cholinergic cell groups in the basal forebrain.(a) Expression of IL-2Rα/mVenus products in the basal forebrain in the Tg mice revealed by immunostaining for mVenus with sections from the MS/vDB and NBM. Scale bars: 200 μm. The brain areas corresponding to light microscopic images are shown in sections modified from an atlas of the mouse brain (Allen Mouse Brain Atlas. Available from: http://mouse.brain-map.org/)53. (b) Cell type-specific expression of transgene products in cholinergic neurons in the MS, vDB, and NMB shown by double immunofluorescence histochemistry for mVenus and ChAT. In a merged image, green signals (mVenus) overlap with red signals (ChAT), thus emitting yellow signals. Scale bars: 200 μm. (c,d) Intracranial injection by using stereotaxic surgery into the MS/vDB (c) or NBM (d). Two cholinergic systems are schematically illustrated in the left panel and injection coordinates are indicated in the right panel in sections modified from the Allen Mouse Brain Atlas http://mouse.brain-map.org/)53. The anteroposterior coordinates (mm) from bregma are shown. Scale bars: 1 mm. (e,f) Immunohistochemical staining for ChAT with sections prepared from the mice 7 days after IT or PBS injection into the MS/vDB (e) or NBM (f). Scale bars: 1 mm. Lower panels show cell counts of ChAT-positive neurons. Data are presented as mean ± s.e.m. n = 5 for each group. *P < 0.05 vs each of other three groups (Bonferroni method). (g) Immunostaining for parvalbumin with sections through the MS/vDB and NBM prepared from the IT-injected mice into the MS/vDB or NBM. Scale bars: 1 mm. Right panel shows cell counts of parvalbumin-positive cells. Data are presented as mean ± s.e.m. n = 5 for each group. (h) AChE staining with sections through the hippocampus (HPC), perirhinal cortex (PRC), and medial prefrontal cortex (mPFC) prepared from the IT-injected mice into the MS/vDB or NBM. Scale bars: 200 μm.
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f1: Selective targeting of cholinergic cell groups in the basal forebrain.(a) Expression of IL-2Rα/mVenus products in the basal forebrain in the Tg mice revealed by immunostaining for mVenus with sections from the MS/vDB and NBM. Scale bars: 200 μm. The brain areas corresponding to light microscopic images are shown in sections modified from an atlas of the mouse brain (Allen Mouse Brain Atlas. Available from: http://mouse.brain-map.org/)53. (b) Cell type-specific expression of transgene products in cholinergic neurons in the MS, vDB, and NMB shown by double immunofluorescence histochemistry for mVenus and ChAT. In a merged image, green signals (mVenus) overlap with red signals (ChAT), thus emitting yellow signals. Scale bars: 200 μm. (c,d) Intracranial injection by using stereotaxic surgery into the MS/vDB (c) or NBM (d). Two cholinergic systems are schematically illustrated in the left panel and injection coordinates are indicated in the right panel in sections modified from the Allen Mouse Brain Atlas http://mouse.brain-map.org/)53. The anteroposterior coordinates (mm) from bregma are shown. Scale bars: 1 mm. (e,f) Immunohistochemical staining for ChAT with sections prepared from the mice 7 days after IT or PBS injection into the MS/vDB (e) or NBM (f). Scale bars: 1 mm. Lower panels show cell counts of ChAT-positive neurons. Data are presented as mean ± s.e.m. n = 5 for each group. *P < 0.05 vs each of other three groups (Bonferroni method). (g) Immunostaining for parvalbumin with sections through the MS/vDB and NBM prepared from the IT-injected mice into the MS/vDB or NBM. Scale bars: 1 mm. Right panel shows cell counts of parvalbumin-positive cells. Data are presented as mean ± s.e.m. n = 5 for each group. (h) AChE staining with sections through the hippocampus (HPC), perirhinal cortex (PRC), and medial prefrontal cortex (mPFC) prepared from the IT-injected mice into the MS/vDB or NBM. Scale bars: 200 μm.
Mentions: We performed the selective elimination of cholinergic neurons in the basal forebrain by using IT-mediated cell targeting2829. The recombinant IT used was anti-Tac(Fv)-PE38, which consists of single-chain variable regions of a monoclonal antibody for human interleukin-2 receptor α-subunit (IL-2Rα) fused to a bacterial exotoxin catalytic fragment. The transgene construct contained the gene cassette encoding human IL-2Rα fused to a variant of enhanced yellow fluorescent protein (mVenus) introduced into the initiation codon site of the gene encoding choline acetyltransferase (ChAT) in a bacterial artificial chromosome clone30 (see Supplementary Fig. S1). The microinjection technique was used to generate multiple independent Tg mouse founders, and one strain, termed ChAT-IL-2Rα/mVenus997-6, expressed the IL-2Rα/mVenus transgene in both the Ms/vDB and NBM regions (Fig. 1a). Double immunofluorescence histochemistry detected mVenus-positive signals in the majority of ChAT-positive neurons, and overlapping signal ratios were 93% and 98% in the MS/vDB and NBM, respectively (Fig. 1b).

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