The pharmacology of amino-acid responses in septal neurons

Septal cholinergic neurons are known to play an important role in cognitive processes including learning and memory through afferent innervation of the hippocampal formation and cerebral cortex. The septum contains not only cholinergic neurons but also various types of neurons including GABA (gamma-aminobutyric acid)-ergic neurons. Although synaptic transmission in the septum is mediated primarily by the activation of excitatory and inhibitory amino-acid receptors, it is possible that a distinct phenotype of neuron is endowed with a different type for each of the amino-acid receptors and thus they play different roles from each other, since it has been demonstrated within the septum that there is a regional distribution of various types of amino-acid receptor subunits, their expression as different combinations within a specific cell may produce receptor channels with disparate functional properties. As a first step towards knowing the various functions of septal cholinergic neurons, we characterized the functional properties of glutamate, GABA (type A; GABAA) and glycine receptor channels on cultured rat septal neurons which were histologically identified to be cholinergic. These were similar to those of receptor channels on other types of neurons, except for the actions of some neuromodulators. The septal N-methyl-D-aspartate receptor channel was distinct in being less sensitive to Mg2+ and in a voltage-dependent action of Zn2+. The septal GABAA receptor channel exhibited a lanthanide site whose activation resulted in a positive allosteric interaction with a binding site of pentobarbital. The septal glycine receptor channel was only positively modulated by Zn2+; this action of Zn2+ was not accompanied by an inhibitory effect. Our data suggest that the amino-acid receptors on septal cholinergic neurons may play a distinct role compared to other types of neurons; this difference depends on the actions of neuromodulators and metal cations. It would be interesting to compare these effects recorded in tissue culture to those observed with septal cholinergic neurons in slice preparations.