Forebrain, basal, cholinergic neurons

Eggermann, E Serafin, M., Bayer, L. et al. (2001). Orexins/hypocretins excite basal forebrain cholinergic neurones. Neuroscience 108, 177-81. 

Jones, B. E. (2004). Activity, modulation and role of basal forebrain cholinergic neurons innervating the cerebral cortex. Prog. Brain Res. 145, 157-69. 

NGF also has actions within the CNS, although it is not particularly abundant in the CNS. Its synthesis appears to be largely restricted to the hippocampus and neocortex, and even in these regions it is present at relatively low concentrations relative to the other neurotrophins. The most prominent population of NGF-responsive neurons expressing TrkA are the basal forebrain cholinergic neurons. The principal projections of these neurons are to the hippocampus and cortex, which conforms with the concept that NGF acts as a target-derived trophic factor in the CNS, just as it does in the peripheral nervous system (PNS). NGF also acts on a subpopulation of cholinergic neurons within the striatum. These interneurons express the NGF receptor, TrkA, and respond to NGF. However, they do not appear to rely entirely on NGF for their survival, and the specific actions of NGF on this neuronal population have not been clearly defined. NGF may also have autocrine actions in the CNS, as some neuronal populations have been identified that express both TrkA and NGF. 

Studies of animals with central cholinergic lesions produced by either pharmacological inhibition of choline uptake or direct excitotoxic lesions of basal forebrain cholinergic neurons have shown highly specific attentional deficits (Muir et al. 1992 Robbins et al. 1989). These animals showed deficits that might be predicted from studies of humans with AD that is, they showed increased response latency and increased responsiveness to irrelevant sensory stimuli. Studies by Vidal (1994b) have shown that administration of a nicotinic antagonist into rat prefrontal cortex impairs performance on spatial... 

The brain of AD patients is also characterized by the degeneration of basal forebrain cholinergic neurons, which innervates central regions involved in cognitive functions such as the cortex amygdala and hippocampus (1,3). The decline of cortical cholinergic activity as measured in postmortem brains... 

Price DL, Whitehouse PJ, Struble RG, Price DL, Cork IC, Hedreen JC, Kitt CA (1983) Basal forebrain cholinergic neurons and neuritic plaques in primate brain. In Katzman R (ed), Biological aspects of Alzheimer s disease. Cold Spring Harbor Laboratory, Cold Spring Harbor, New York, p 65... 

Lesioned animal models are based upon the assumption that the destruction of basal forebrain cholinergic neurons by injection of a neurotoxin, such as ibotenic acid, is sufficient to reproduce some of the cognitive impairments associated with AD, mainly memory and learning deficits. Indeed, pathology in the basal forebrain... 

Thus, no consensual conclusion is available about the behavioural and cognitive effects of basal forebrain cholinergic neuron lesions in nonhuman primates. However, one has to keep in mind that AD is not solely a disease of the cholinergic system. 

The neurotrophin NGF is essential for the maintenance and differentiation of basal forebrain cholinergic neurons. Alterations in NGF transport and signaling play a crucial role in sporadic AD neurodegeneration, leading to the hypothesis of neurotrophic imbalance as an upstream driver for sporadic AD [73]. 

Henderson, Z., Responses of basal forebrain cholinergic neurons to damage in the adult brain, Prog. Brain Res., 48, 219, 1996. 

Koliatsos, V. E., Nauta, H. J., Clatterbuck, R. E., Holtzman, D. M., Mobley, W. C., and Price, D. L., Mouse nerve growth factor prevents degeneration of axotomized basal forebrain cholinergic neurons in the monkey, J. Neurosci., 10, 3801, 1990. 

Widmer, H. R., Rnusel, B., and Hefti, F., BDNF protection of basal forebrain cholinergic neurons after axotomy complete protection of p75NGFR-positive cells, Neuroreport, 4, 363, 1993. 

Williams, L. R., Inouye, G., Cummins, V., and Pelleymounter, M. A., Glial cell line-derived neurotrophic factor sustains axotomized basal forebrain cholinergic neurons in vivo dose-response comparison to nerve growth factor and brain-derived neurotrophic factor, J. Pharmacol. Exp. Then, 277, 1140, 1996. 

Hatanaka, H., Tsukui, H. and Nihonmatsu, 1. (1988) Developmental change in the nerve growth factor action from induction of choline acetyltransferase to promotion of cell survival in cultured basal forebrain cholinergic neurons from postnatal rats. Dev. Brain Res. 39 85-95. 

Phillips, H.D., Hains, J.M., Laramee, G.R., Rosenthal, A. and Winslow, J.W. (1990) Widespread expression of BDNF but not NT-3 by target areas of basal forebrain cholinergic neurons. Science 250 290-294. 

Finally, NT-3 has recently been shown to increase the levels of several neuropeptides, including somatostatin and substance P, in cortex, hippocampus and striatum of neoanatal rats (Carnahan and Nawa, 1995). If this action persists in adult animals, it may offer the possibility of NT-3 being used in Alzheimer s disease to rescue not only basal forebrain cholinergic neurons but also cortical peptidergic neurons. 

Adult Basal forebrain Cholinergic neurons Yes Axotomy Alderson et al., 1996... 

Basal forebrain Cholinergic neurons Spatial memory Aged Fisher et al., 1994... 

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