Cholinergic modulation of epileptiform activity in the developing rat neocortex

The effects of carbachol on picrotoxin-induced epileptiform
activity and membrane properties of neurons in the developing rat
neocortex were examined in an in vitro slice preparation.
Intracellular recordings were obtained in layer II–III neurons of
slices prepared from rats 9–21 days of age. Epileptiform activity
in 9- to 14-day-olds consisted of a sharply rising, sustained
(10–30 s) membrane depolarization with superimposed action
potentials. Bath application of carbachol (5–50 μM) raised the
threshold for evoking epileptiform activity but, when such
responses were evoked, their underlying depolarizations were
increased in amplitude. Orthodromic stimulation in slices from 15-
to 21-day-old animals evoked a prolonged epileptiform burst
response that triggered an episode of spreading depression (SD).
Carbachol reduced epileptiform responses and suppressed the
occurrence of SD. It did not significantly affect the resting
membrane potential or the height of the action potential but
decreased the rheobase current needed to evoke an action potential
and increased the input resistance. All effects of carbachol were
antagonized by atropine (1 μM). These results indicate that
carbachol has both pre- and postsynaptic effects in the developing
neocortex and can significantly modulate neuronal excitability in
the immature nervous system.