Mechanisms of association learning in the post-synaptic neurone

A general mechanism for association learning in neurones is presented based on the biochemistry and electrophysiology of synaptic receptor regions. The mechanism involves the voltage sensitive generation of second messengers in the post-synaptic neurone, and their subsequent influence on the sensitivity of the local receptor region. The mechanism is examined in detail using a computer model of the reaction dynamics of two important synaptic receptors; the adrenergic receptor and the NMDA-type glutamate receptor. The computer model simulates concentration changes of several molecules in the post-synaptic neurone following an input to a receptor. It also models changes in membrane potential caused by the cell firing, and allows for the impact of these potential changes on second messenger generation within the cell. Finally the model incorporates two possible mechanisms whereby high concentrations of second messenger can lead to long-lasting changes in receptor sensitivity. The model demonstrates an enhancement of synaptic response when previous inputs to the same receptor region have occurred when the cell was firing. Using the model, long term potentiation (LTP) of the glutamate response is demonstrated following a high frequency input to the glutamate receptor. A neurone with ten glutamate receptors is simulated and demonstrates that individual neurones should be capable of recognising patterns of input activity when those patterns have repeatedly occurred at times of major cellular activity.