Control of the mammillothalamic axis by brainstem cholinergic laterodorsal tegmental afferents: Possible involvement in mnemonic processes

Abstract

Abstract Learning is generally thought to involve lasting modifications in the connections between neurons (Squire 1987). Such durable changes in synaptic efficacy were first observed at the level of the synapse between perforant path fibres and dentate granule cells following tetanic stimulation of afferent fibres (Bliss and Lom0 1973; Bliss and Gardner-Medwin 1973). The long-term potentiation (LTP) induced by this procedure lasted for hours and was homosynaptic, that is, it was restricted to the tetanized pathway. More recently, iontophoretically-applied ACh has been shown to produce lasting changes in cellular responsiveness at the cortical level (see Chapter 11 in this book). We now report that stimulation of the brainstem cholinergic laterodorsal tegmental (LDT) nucleus can induce a long-lasting enhancement in the synaptic responsiveness of anterior thalamic (AT) neurons to both cortical and subcortical inputs. Such cholinergic effects and especially those of synapticallyreleased ACh had not been demonstrated previously in the dorsal thalamus. The AT complex is, through the mammillary nuclei (MN), intimately linked to the hippocampal formation, a neuronal structure believed to be critical for memory processes. The first section in this chapter is a brief overview of the connections between the LDT nucleus, the AT nuclear complex, the MN, and the hippocampal formation. The second section summarizes a recent series of experiments designed to study the effects of LDT stimulation on AT neurons. The enhancement in synaptic responsiveness induced by LDT stimulation will be compared to the hippocampal LTP. We then discuss the relevance of these findings for memory processes in the light of the neuropathological studies implicating the medial diencephalon and the hippocampal formation in amnesia.