Effects of cholinergic agonists on immature rat hippocampal neurons

We have investigated the effects of acetylcholine (ACh) and the cholinergic agonist carbachol on several cell types in the developing rat hippocampus. Pyramidal cells were responsive to cholinergic applications on the first day examined (postnatal day 2), indicating that postsynaptic cholinoceptivity develops early, perhaps before functional cholinergic innervation is present. These drugs, which induce a membrane depolarization and a conductance decrease in mature pyramidal cells, had similar effects (both magnitude and pharmacology) on most immature neurons. However, a minority of cells in immature tissue exhibited decreased input resistance (Rin) during the cholinergic-induced depolarization. This response is likely a product of cholinergic action on local circuit neurons: non-pyramidal-type cells from animals as young as 8 days demonstrated excitatory responses to application of cholinergic agonists. The study revealed a number of other features of immature cells which may have functional significance. Lucifer yellow injections showed significant dye coupling among CA3 (but not CA1) pyramidal cells in immature tissue, suggesting close metabolic and/or electrotonic coupling between those cells during development. Mature CA3 cells showed less dye coupling, but increased anomalous rectification, and longer time constant. Developmental changes in intrinsic cell properties, coupled to alterations in local circuit interactions, may alter tissue responsiveness to neurotransmitters such as acetylcholine, even if the receptor-mediated drug action remains stable.