Histaminergic neurons form the tuberomammillary nucleus of the posterior hypothalamus (Panula et al., 1984; Watanabe et al., 1984; Airaksinen and Panula, 1988). The TM nucleus represents the main source of histamine in the central nervous system and projects axons throughout the brain, including to the hippocampal formation and cerebellum (Watanabe et al., 1984; Airaksinen et al., 1991). The TM nucleus is involved in learning and memory formation and in regulating multiple functions such as sleep and wakefulness, energy and hormonal metabolism, eating, drinking and sexual behavior (Schwartz et al., 1991; Wada et al., 1991). Numerous neurofibrillary tangles have been found in the TM nucleus of patients with Alzheimer's disease (Saper and German, 1987; Airaksinen et al., 1991; Nakamura et al., 1993). Histamine neurons participate in a complex net of neurotransmit-ter/neuromodulator-receptor interactions (Haas and Reiner, 1988; Greene et al., 1990; Uteshev et al., 1996) and exhibit high concentrations of a-btx binding sites that are consistent with the expression of a7-containing nicotinic receptor (Clarke et al., 1985). It has recently been demonstrated electrophysiologically (Uteshev et al., 1996; Papke et al., 2000) that neurons acutely dissociated from the TM nucleus express high levels of nicotinic receptor that demonstrate the rapid desensitization kinetics characteristic of a7 receptors are fully sensitive to blockade by a-btx, and are activated by the a7-selective agonist 4OH-GTS-21.

alpha7 receptor responses in various systems

Rat brain being sectioned for TM neuron isolation

TM neurons in IR imaging

Fast agonist application

Partial agonist occupancy model for alpha7 activation

Hypothetical states of the alpha7 receptor

Low agonist concentration provided the most alpha7 activation over time


References