Serotonergic control of cerebral activity and behavior: models of dementia.

Recent evidence indicates that the ascending cholinergic projections from the basal forebrain and the ascending serotonergic projections from the brain stem exert a powerful control over the generalized electrical activity of the hippocampal formation and neocortex.' These inputs have a very general effect, altering the pattern of unitary activity and the development of evoked potentials as well as spontaneous slow wave activity. However, a number of the basic effects can be conveniently studied using spontaneous slow wave recording techniques in freely moving animals.' One of the results of cholinergic and serotonergic inputs to the hippocampal formation in normal rats is the generation of rhythmical slow activity (RSA) which, during waking, occurs in close correlation with spontaneous motor activities such as walking, changing posture, turning or raising the head, and manipulating objects with the forelimbs (Type 1 behavior). During other behaviors such as standing or lying immobile, face-washing, chewing, gnawing, licking, or shivering (Type 2 behavior) hippocampal activity is usually quite irregular (large amplitude irregular activity, LIA) but RSA can be elicited by a variety of experimental procedures. Such RSA appears to be dependent on cholinergic inputs to the hippocampus while the RSA occurring during Type 1 behavior is dependent on both cholinergic and serotonergic inputs. Neocortical activity also appears to be under the control of ascending cholinergic and serotonergic inputs although the generalized patterns of electrical activity present in the neocortex differ in several respects from the patterns occurring in the hippocam-pal formation. During Type 1 behavior, low voltage fast activity (LVFA) is always present as a result of combined cholinergic and serotonergic inputs. During Type 2 behavior, LVFA is often present but large irregular slow waves or rhythmical spindles may be present instead, especially during behavioral immobility. Any LVFA that occurs during Type 2 behavior appears to be dependent on cholinergic inputs to the neocortex while the LVFA occurring during Type 1 behavior is dependent on both cholinergic and serotonergic inputs. Thus, the control of neocortical LVFA appears to parallel closely the control of hippocampal RSA. The effects of serotonergic control of cortical activity can be observed in the absence of the masking effect of concurrent cholinergic activity following the administration of centrally-acting anti-muscarinic drugs. The hippocampal RSA and neocorti-cal LVFA that persist after such treatment can be referred to as atropine-resistant RSA and atropine-resistant LVFA even though other anti-muscarinic drugs (ditran,