Extensive evidence indicates that disruption of cholinergic function is characteristic of aging and Alzheimer's disease (AD), and experimental manipulation of the cholinergic system in laboratory animals suggests age-related cholinergic dysfunction may play an important role in cognitive deterioration associated with aging and AD. Recent research, however, suggests that cholinergic dysfunction does not provide a complete account of age-related cognitive deficits and that age-related changes in cholinergic function typically occur within the context of changes in several other neuromodulatory systems. Evidence reviewed in this paper suggests that interactions between the cholinergic system and several of these neurotransmitters and neuromodulators--including norepinephrine, dopamine, serotonin, GABA, opioid peptides, galanin, substance P, and angiotensin II--may be important in learning and memory. Thus, it is important to consider not only the independent contributions of age-related changes in neuromodulatory systems to cognitive decline, but also the contribution of interactions between these systems to the learning and memory deficits associated with aging and AD.

The role of interactions between the cholinergic system and other neuromodulatory systems in learning and memory.

The basal forebrain cholinergic projection (BFC) system has been the focus of considerable attention as a result of evidence implicating it in a number of behavioral functions, including arousal, sensory processing, motivation, emotion, learning, and memory (Deutsch, 1983; Buzsaki et al., 1988; Richardson and DeLong, 1988; Durkin, 1989; Rolls 1989, Steriade and McCarley, 1990). Moreover, neuropathological changes in the BFC have been reported in a surprisingly large number of neurological diseases, including Alzheimer’s and Parkinson’s diseases (for ref. see Coyle et al., 1983; Mesulam and Geula, 1988; Arendt et al., 1989). BFC neurons in the rat are dispersed across a number of classically defined territories of the basal forebrain, as illustrated from a series of coronal sections in Fig. 1. However, using a computer graphic three-dimensional reconstruction technique (Schwaber et al., 1987) or manual reconstruction from camera lucida drawings (Fig. 2) it is evident that BFC neurons form a continuum, rather than being arranged as distinct nuclear groups.

Afferents to basal forebrain cholinergic projection neurons: an update.

The role of neuropeptides in learning: focus on the neurokinin substance P.

Modulation of memory processing by neuropeptide Y varies with brain injection site

Intraseptal administration of muscimol produces dose-dependent memory impairments in the rat.

The neuropeptide substance P (SP) was injected into the region of the nucleus basalis magnocellularis (NBM). The influence of SP on the performance of the single trial “uphill avoidance task” was tested. The post-trial injection of 1 ng SP (in 0.5 μl volume) led to significantly longer latencies in the uphill response. This result can be interpreted in terms of a facilitating effect of SP on performance of an inhibitory avoidance response.

M.-S. Holzhäuer

Papers

Substance P injected into the region of the nucleus basalis magnocellularis facilitates performance of an inhibitory avoidance task