The Cholinergic Synapse and the Site of Memory

Abstract

A simple hypothesis can explain the results obtained to date if we disregard those results when we wait 30 minutes after original learning to inject. The hypothesis is that, as a result of learning, the postsynaptic endings at a specific set of synapses become more sensitive to transmitter. This sensitivity increases with time after initial learning and then declines. The rate at which such sensitivity increases depends on the amount of initial learning. If the curve of transmission plotted against time is displaced upward with anticholinesterases then the very low portions will show facilitation, and the high portions will cause block (Fig. 8). The middle portions will appear unaffected (unless special experimental tests are made). If the curve of transmission is displaced down with anticholinergics, then the middle portion will appear unaffected and only the very early or late components will show block. The results are evidence that synaptic conductance is altered as a result of learning. So far it seems (i) that cholinergic synapses are modified as a result of learning and that it probably is the postsynaptic membrane that becomes increasingly more sensitive to acetylcholine with time after learning, up to a certain point. (ii) After this point, sensitivity declines, leading to the phenomenon of forgetting. (iii) There is also good evidence that there is an initial phase of declining sensitivity to cholinesterase or increasing sensitivity to anticholinergics. This could reflect the existence of a parallel set of synapses with fast decay that serve as a shortterm store. (iv) Increasing the amount of learning leads to an increase in conductance in each of a set of synapses without an increase in their number. (v) Both original learning and extinction are subserved by cholinergic synapses.

Cholinergic ventral forebrain grafts into the neocortex improve passive avoidance memory in a rat model of Alzheimer disease.

“…The memory deficit characteristic of Alzheimer disease has been attributed to this cholinergic loss (7,8), although involvement of other neurotransmitters cannot be excluded (9,10). In animal experiments, both anticholinergic drugs (11) and lesions of the NBM (12)(13)(14) have been shown to disrupt learning or memory in a number of paradigms, the most sensitive of which has been the passive avoidance test. It has also been shown that transplanted embryonic neurons can reinnervate the rat brain to restore certain functions of dopaminergic (15,16) or cholinergic (17) systems in rats with NBM lesions.…”

The Effect of Sublethal Concentration of Decis 2.5 Ec Pesticide on Learning and Memory Processes in Common Carp,<I> Cyprinus Carpio</I> (Actinopterygii: Cypriniformes: Cyprinidae)

“…8). It seems that one of the reasons could be inhibiting synaptic conduction by the pyrethroid what was proved by numerous studies (Deutsch 1971, D'Mello 1993, Pan and Dutta 1998, Csilik et al 2000.…”

“…While shortterm memory is concerned, there is a temporary increase in sensitivity of synapses to neurotransmitter and in longterm memory-sensitivity of synapses to the consecutive stimulation is constant in character (Deutsch 1971, Mamounas et al 1987, Tronel et al 2004). …”

On a Fractional Stochastic Path Integral Approach in Modelling Interneuronal Connectivity

“…At the cellular level, various experiments, indicate that memory is encoded by changes in the synaptic strength or connectivity between communicating neuronal cells in the brain. [3][4][5][6] These considerations lead us to an analytical framework whose elements could be matched vis-á-vis biological features. First, we use the Feynman path integral approach since it precisely works for systems with large numbers of degrees of freedom, having been conceptually designed to work as a 'summation over all possible histories' of a physical system.…”