The Critical Role of Cholinergic Basal Forebrain Neurons in Morphological Change and Memory Encoding: A Hypothesis

It has been known for a long time that cholinergic basal forebrain neurons which project to the cerebral cortex play a role in learning and memory. Behavioral studies following lesions, for example, repeatedly have suggested multiple learning-related roles for these neurons. Apart from behavioral studies, cholinergic neurons have been shown to possess extraordinarily plastic axons. This plasticity has not been related comprehensively to mnemonic devises, even though morphological changes in the CNS are prime candidates for the neural engram. In this paper, I propose a hypothesis that relates these two characteristics of cholinergic neurons. This hypothesis is that plastic cholinergic axon terminals induce structural reorganization in their targets during memory storage. Possible intracellular mechanisms are examined, whereby acetylcholine release in the cerebral cortex could cause postsynaptic structural changes. Finally, the characteristics of the overall cholinergic–cholinoceptive cell “engram” are elaborated with particular attention paid to the encoding of the stimulus properties along with the context and meaning of the stimulus.