Hippocampal grafts of acetylcholine-producing cells are sufficient to improve behavioural performance following a unilateral fimbria–fornix lesion

Dickinson-Anson, Heather; Aubert, Isabelle; Gage, Fred H.; Fisher, Lisa J.

doi:10.1016/s0306-4522(97)00543-5

Cited by 39 publications

(26 citation statements)

References 71 publications

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“…Similarly, delivery of adeno-associated virus (AAV) vectors, lentivirus vectors, or adenovirus vectors that express NGF into specific basal forebrain nuclei protects cholinergic neurons from degeneration in aged rats, or following transection of the fimbria-fornix, and improved spatial learning (Blesch et al, 2005; Klein et al, 2000; Mandel et al, 1999; Wu et al, 2005; Wu et al, 2004; Zou et al, 2002). In another approach, also using either aged rats or transection of the fimbria-fornix, fibroblasts genetically engineered to express choline acetyltransferase, and transplanted into the hippocampus or neocortex, supported improved spatial learning (Dickinson-Anson et al, 1998; Dickinson-Anson et al, 2003). Strategies using either a neurotrophic factor or acetylcholine are designed to modulate the activity of hippocampal or cortical neurons.…”

Section: Discussionmentioning

confidence: 99%

Improved spatial learning in aged rats by genetic activation of protein kinase C in small groups of hippocampal neurons

Zhang¹,

Li²,

Kong³

et al. 2008

Hippocampus

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Age-related declines in human cognition are well known, and there are correlative changes in the function of neocortical and hippocampal neurons. Similarly, age-related declines in learning have been observed in rodents, including deficits in a hippocampal-dependent learning paradigm, the Morris water maze. Furthermore, there are correlative deficits in specific signaling pathways, including protein kinase C (PKC) pathways, in cerebellar, hippocampal, or neocortical neurons. PKC pathways are strong candidates for mediating the molecular changes that underlie spatial learning, as they play critical roles in neurotransmitter release and synaptic plasticity, including long-term potentiation (LTP) and long-term depression (LTD), and deletion of specific PKC genes results in deficits in learning. Conversely, genetic activation of PKC pathways in small groups of hippocampal or cortical neurons enhances learning in specific paradigms. In this study, we delivered a constitutively active PKC into small groups of hippocampal dentate granule neurons in aged rats (using a Herpes Simplex Virus-1 vector). Aged two-year old rats that received the constitutively active PKC displayed improved performance in the Morris water maze relative to controls in three different measures. These results indicate that PKC pathways play an important role in mediating spatial learning in aged rats. Additionally, these results represent a system for studying the neural mechanisms underlying aging-related learning deficits, and potentially developing gene therapies for cognitive and age-related deficits.

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Section: Discussionmentioning

confidence: 99%

Improved spatial learning in aged rats by genetic activation of protein kinase C in small groups of hippocampal neurons

Zhang¹,

Li²,

Kong³

et al. 2008

Hippocampus

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“…Extensive evidence indicates that the septo-hippocampal system is involved in memory processes (Galey et al 1989;Marighetto et al 1989;Ammassari-Teule and Maho 1992;Dalrymple-Alford 1994;Izquierdo and Medina 1995). For instance, lesions of the fimbria-fornix produce robust memory deficits (Nilsson et al 1987;Aggleton et al 1992;Dickinson-Anson et al 1998).…”

mentioning

confidence: 99%

“…In some instances, IgG saporin-induced lesions of the cholinergic septo-hippocampal projection impair spatial working memory (BergerSweeney et al 1994;Dornan et al 1996;Walsh et al 1996; also see Baxter et al 1995;Bannon et al 1996;Pang and Nocera 1998). Furthermore, hippocampal grafts of ACh-producing cells attenuate the memory-impairing effects of fimbria-fornix lesions (Dunnett et al 1982;Nilsson and Björk-lund 1992;Dickinson-Anson et al 1998).…”

mentioning

confidence: 99%

Increasing Acetylcholine Levels in the Hippocampus or Entorhinal Cortex Reverses the Impairing Effects of Septal GABA Receptor Activation on Spontaneous Alternation

Degroot¹,

Parent²

2000

Learn. Mem.

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Intra-septal infusions of the ␥-aminobutyric acid (GABA) agonist muscimol impair learning and memory in a variety of tasks. This experiment determined whether hippocampal or entorhinal infusions of the acetylcholinesterase inhibitor physostigmine would reverse such impairing effects on spontaneous alternation performance, a measure of spatial working memory. Male Sprague-Dawley rats were given intra-septal infusions of vehicle or muscimol (1 nmole/0.5 µL) combined with unilateral intra-hippocampal or intraentorhinal infusions of vehicle or physostigmine (10 µg/µL for the hippocampus; 7.5 µg/µL or 1.875 µg/0.25 µL for the entorhinal cortex). Fifteen minutes later, spontaneous alternation performance was assessed. The results indicated that intra-septal infusions of muscimol significantly decreased percentage-of-alternation scores, whereas intra-hippocampal or intra-entorhinal infusions of physostigmine had no effect. More importantly, intra-hippocampal or intra-entorhinal infusions of physostigmine, at doses that did not influence performance when administered alone, completely reversed the impairing effects of the muscimol infusions. These findings indicate that increasing cholinergic levels in the hippocampus or entorhinal cortex is sufficient to reverse the impairing effects of septal GABA receptor activation and support the hypothesis that the impairing effects of septal GABAergic activity involve cholinergic processes in the hippocampus and the entorhinal cortex.Extensive evidence has implicated the medial septum in learning and memory. Lesions of the medial septum impair acquisition and retention performance in a variety of behavioral paradigms (Mitchell et al. 1982;Bolhuis et al. 1988;Fibiger et al. 1991;M'Harzi and Jarrard 1992). Furthermore, memory can be enhanced or impaired by intra-septal infusions of drugs that act at a variety of neurotransmitter systems (Brioni et al. 1990;Givens and Olton 1990;Markowska et al. 1990). For example, intra-septal infusions of ␥-aminobutyric acid (GABA)ergic agonists impair memory during numerous tasks, including radial arm maze performance, inhibitory avoidance, water maze performance, spontaneous alternation, rewarded alternation, and visual discrimination (Brioni et

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“…These neurons retrogradely transport NGF (Schwab et al, 1979;Seiler and Schwab, 1984) and appear to be NGF dependent based on their vulnerability to the loss of NGF and their subsequent rescue by exogenous NGF (Hefti, 1986;Williams et al, 1986;Kromer, 1987;Rosenberg et al, 1988). Lesion of these projections interferes in the performance of complex learning and memory tasks (Dunnett, 1990), which can be attenuated following regeneration of cholinergic projections across a bridging graft (Eagle et al, 1995) or grafting acetylcholine-producing cells to the hippocampus (Dickinson-Anson et al, 1998).…”

mentioning

confidence: 99%

Central neuronal loss and behavioral impairment in mice lacking neurotrophin receptor p75

et al. 1999

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Hippocampal grafts of acetylcholine-producing cells are sufficient to improve behavioural performance following a unilateral fimbria–fornix lesion

Cited by 39 publications

References 71 publications

Improved spatial learning in aged rats by genetic activation of protein kinase C in small groups of hippocampal neurons

Improved spatial learning in aged rats by genetic activation of protein kinase C in small groups of hippocampal neurons

Increasing Acetylcholine Levels in the Hippocampus or Entorhinal Cortex Reverses the Impairing Effects of Septal GABA Receptor Activation on Spontaneous Alternation

Central neuronal loss and behavioral impairment in mice lacking neurotrophin receptor p75

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