Responses of morphologically identified cortical neurons to intracellularly injected cyclic GMP

Cyclic nucleotides are thought to act as second messengers of neurotransmission inside central neurons, and cyclic guanosine monophosphate (cGMP) has been postulated to act as a messenger for muscarinic, cholinergic transmission. Nonetheless, the action of cGMP has not yet been established in identified cortical neurons. We injected cGMP and horseradish peroxidase (HRP) intracellularly in neurons of the motor cortex of awake cats. Fifty-four percent of injected cells responded to cGMP and HRP with an increase in input resistance within 30 s after injection. None of a control group of cells injected with HRP without cGMP so responded. In cells receiving intracellular depolarizing current sufficient to produce repeated spike discharge at the time of injection, the increase in input resistance after cGMP persisted for as long as the cells could be held. There was no significant increase in firing rate after injection of cGMP. Cells responding to cGMP with an increased input resistance were identified as pyramidal cells of layer V. One inverted pyramidal cell of layer VI also showed an increase in input resistance in response to cGMP. Previous studies have suggested that muscarinic cholinergic agents produce an increased input resistance (thought to reflect a decreased potassium conductance) underlying an increased rate of discharge in neocortical neurons. Our results favor a dual action of muscarinic cholinergic transmission in mammalian cortical neurons--the increase in input resistance in layer V pyramidal cells mediated by cGMP, and the increase in rate of discharge mediated by other means.