Nicotinic receptor mechanism in supramammillary nucleus mediates physiological regulation of neural activity in dorsal hippocampal field CA1 of anaesthetized rat

Abstract

Evidence suggests that stimulation of the region of the rostral pontine oralis (RPO) nucleus and the peripheral application of a noxious stimulus activates an ascending system that also modulates hippocampal neural responses during behavioral arousal. Indeed, the two stimuli and behavioral arousal elicit theta activation and the suppression of population spikes (PS) in dorsal hippocampus field CA1. Interestingly, such neural responses in CA1 are also elicited by microinjection of the cholinergic agonist carbachol into the hypothalamic supramammillary nucleus (SuM). In the present in vivo electrophysiological study, we tested the hypothesis that cholinergic neural elements in the SuM modulate the neural drive to CA1 on RPO stimulation or the peripheral application of a noxious stimulus. Pharmacological investigation showed that intra-SuM microinjection of either a muscarinic or a nicotinic receptor antagonist attenuated the SuM carbachol-induced neural effects in CA1, namely, theta activation and PS suppression. However, neither antagonist attenuated the CA1 effects of intra-SuM microinjection of the excitatory neurotransmitter glutamate. Subsequent investigations revealed that microinjection of only the nicotinic antagonist, mecamylamine, into the lateral SuM selectively attenuated the responses elicited in CA1 by stimulation of the RPO or on nociceptive stimulation with hind paw injection of formalin (5%, 0.05 ml); whereas, microinjection of mecamylamine into the medial SuM did not affect the hippocampal responses elicited by either type of stimulation. Furthermore, application of mecamylamine into the lateral SuM attenuated the CA1 responses induced by injection of formalin into the contralateral, but not the ipsilateral hind paw. The lateralization of drug effect is consistent with the predominant unilateral anatomical connections between the SuM and the septohippocampal region. These findings provide novel evidence that nicotinic cholinoceptive neurons in the lateral SuM are common elements of the neural drive(s) to the hippocampus on RPO activation and noxious stimulation.