Cholinergic system basal forebrain

The development of antibodies against ChAT allowed the distribution of neurons producing acetylcholine in the nervous system to be revealed (Mesulam et al., 1983 Armstrong et al., 1983 Jones Beaudet, 1987 Vincent Reiner, 1987). In the context of control of wakefulness and REM sleep two groups of cholinergic neurons are of primary importance. Neurons located in the basal forebrain and medial septum provide the cholinergic innervation of the cerebral... 

Berntson, G. G., Shafi, R. Sarter, M. (2002). Specific contributions of the basal forebrain corticopetal cholinergic system to electroencephalographic activity and sleep/waking behaviour. Eur. J. Neurosci. 16, 2453-61. 

The basal forebrain is an important way station in the activation of the cerebral cortex from the reticular activating system. AMPA and NMDA injections into the basal forebrain increase wakefulness and reduce sleep (Cape Jones, 2000 Manfridi et al, 1999), effects that are blocked by AMPA and NMDA receptor antagonists (Manfridi et al, 1999). The excitatory cortical projections of the basal forebrain have long been considered purely cholinergic, but many basal forebrain neurons that project to the cortex are now known to contain Glu, which may function as a co-transmitter or even as the primary excitatory neurotransmitter (Manns et al, 2001). The basal forebrain also affects vigilance via synapses to HCT cells in the lateral hypothalamus some of these synapses are glutamatergic (Henny Jones, 2006). 

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. 

Figure 2. The cholinergic system in the human brain. The two principal pathways projecting from discrete nuclei are shown as basal forebrain (continuous lines) and pedunculopontine/dorsal tegmental (dotted lines).

Lesions of the basal forebrain cholinergic system using a-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid (AMPA) result in impaired attentional, but not mnemonic, function in rats (Muir et al., 1995) and monkeys (Voytko et al., 1994), an effect which has been confirmed using more selective IgG-saporin lesions (Baxter et al., 1995 Everitt 8c Robbins, 1997). 

Recent research has indicated select abnormalities in the cholinergic system (Perry et al., 2001). Although previously unexamined neurochemically, there was an indication that the cholinergic system may be involved in autism, with abnormalities reported in neurons in the basal forebrain (Bauman Kemper, 1994). Perry et al. (2001) found extensive loss of high affinity nicotinic receptors from the neocortex (frontal and parietal), and from the cerebellum (Lee, et al., in preparation). Nicotinic receptors are implicated in attention, and also consciousness as many general anaesthetics block the receptor channel (Chapter 9). 

---