Cholinergic regulation of neocortical spindling in DBA/2 mice

Brief episodes of high-amplitude, bilaterally synchronous, seven-cycles-per-second spindles appear in the EEG of DBA/2 inbred mice during active waking, quiet waking, and slow-wave sleep. They do not occur during waking in C57BL/6 mice. This difference might result from differences in acetylcholine-mediated arousal as nicotine powerfully blocks brief spindle episodes in awake DBA/2 mice. The following results are reported. (i) Physostigmine (0.1 and 0.3 mg/kg, i.p.) desynchronized the EEG and produced behavioral immobility, but did not block brief spindle episodes in free-moving DBA/2 mice. (ii) Atropine (1.0 mg/kg, i.p.) reduced arousal and provoked slow waves without facilitating brief spindle episodes. (iii) Mecamylamine (1.0 mg/kg, i.p.) weakly activated spindles without producing any noticeable behavioral alterations. Because these treatments had little effect on spindle occurrence, the action of nicotine in brain stem-transected DBA/2 mice was investigated. Nicotine (1.0 mg/kg, i.p.) had no effect on brief spindle episodes released by rostropontine transection but powerfully blocked those provoked by pentylenetetrazol (20 mg/kg, i.p.) in midpontine-transected mice. Hence nicotine's antispindling action may be mediated in the rostral pons. As both nicotine and physostigmine produce behavioral immobility and EEG activation in free-moving DBA/2 mice, but only nicotine inhibits cortical spindling, the mechanisms that produce EEG desynchronization are probably not identical to those that prevent spindling. They may, though, be linked, parallel processes that are somehow dissociated in DBA/2 mice.