Functional requirements determine relevant ingredients to model for on-line acquisition of context dependent memory

Biophysical simulations of memory must choose which aspects of known neurophysiology and neuroanatomy to model. Relevant aspects were constrained by functional requirements determined for on-line acquisition in context dependent memory, memory that is retrieved by contextual cues. In an on-line task, the protocol of data presentation and the tunes at which encoding or retrieval in memory is needed are not predetermined. A sequence of neuronal spike patterns representing items may be presented only once. Yet, episodic memory of the sequence immediately encodes the temporal context of familiar items, a process known to depend on hippocampal function. For this, interference caused by overlapping spike patterns must be avoided, a requirement that suggested the relevance of coincidental spiking. Overlap in the input to the hippocampus was reduced by recruiting such spikes in a model of encoding in dentate gyrus. Durable encoding is required in the hippocampus, since hippocampal damage can cause retrograde amnesia in context dependent memory that spans years. Long-lasting synaptic changes involved modeling relevant neurophysiology concerning protein production elicited by the spaced reactivation of spike patterns. The likelihood of reactivation was increased by the well-known process of long-term potentiation of synaptic transmission. Such potentiation is elicited when a presynaptic spike precedes a postsynaptic spike within a specific time window repeatedly. The intervals in a sequence of spike patterns must be compressed and the sequence repeated, requirements that were achieved with a model of short-term memory based on persistent spiking. Retrieval may be concurrent with these encoding processes due to effects of different phases of a brain rhythm at theta frequency (3-12 Hz) that modulate transmission and plasticity. A model of short-term memory by Lisman and Idiart (Science 267:1512-15), extended by Jensen et al. (Learning and Memory 3:24