MODULATION OF ASSOCIATIVE MEMORY FUNCTION IN A BIOPHYSICAL SIMULATIONOF RAT PIRIFORM CORTEX

1. Associative memory function was analyzed in a realistic biophysical simulation of rat piriform (olfactory) cortex containing 240 pyramida l cells and 58 each of two types of inhibitory interneurons. Pyramidal cell simulations incorporated six different intrinsic currents and th ree different synaptic currents. We investigated the hypothesis that a cetylcholine sets the appropriate dynamics for learning within the net work, whereas removal of cholinergic modulation sets the appropriate d ynamics for recall. The associative memory function of the network was tested during recall after simulation of the cholinergic suppression of intrinsic fiber synaptic transmission and the cholinergic suppressi on of neuronal adaptation during learning. 2. Hebbian modification of excitatory synaptic connections between pyramidal cells during learnin g of patterns of afferent activity allowed the model to show the basic associative memory property of completion during retail in response t o degraded versions of those patterns, as evaluated by a performance m easure based on normalized dot products. 3. During learning of multipl e overlapping patterns of afferent activity, recall of previously lear ned patterns interfered with the learning of new patterns. As more pat terns were stored this interference could lead to the exponential grow th of a large number of excitatory synaptic connections within the net work. This runaway synaptic modification during learning led to excess ive excitatory activity during recall, preventing the accurate recall of individual patterns. 4. Runaway synaptic modification of excitatory intrinsic connections could be prevented by selective suppression of synaptic transmission at these synapses during learning. This allowed effective recall of single learned afferent patterns in response to de graded versions of those patterns, without interference from other lea rned patterns. 5. During learning, cholinergic suppression of neuronal adaptation enhanced the activity of cortical pyramidal cells in respo nse to afferent input, compensating for decreased activity due to supp ression of intrinsic fiber synaptic transmission. This modulation of a daptation led to more rapid learning of afferent input patterns, as de monstrated by higher values of the performance measure.6. During recal l, when suppression of excitatory intrinsic synaptic transmission was removed, continued cholinergic suppression of neuronal adaptation led to the spread of excessive activity. More stable activity patterns dur ing recall could be obtained when the cholinergic suppression of neuro nal adaptation was removed at the same time as the cholinergic suppres sion of synaptic transmission. 7. A realistic biophysical simulation o f the effects of acetylcholine on synaptic transmission and neuronal a daptation in the piriform cortex shows that these effects act together to set the appropriate dynamics for learning, whereas removal of both effects sets the appropriate dynamics for recall.