CHOLINERGIC MODULATION OF ACTIVITY-DEPENDENT SYNAPTIC PLASTICITY IN THE PIRIFORM CORTEX AND ASSOCIATIVE MEMORY FUNCTION IN A NETWORK BIOPHYSICAL SIMULATION

The effect of activation of cholinergic receptors on long-term potenti ation (LTP) in rat piriform cortex pyramidal cells was studied using e xtracellular and intracellular recordings in brain slice preparations. The functional role of this modulation was studied in a realistic net work biophysical simulation. Repetitive stimuli were applied in two pa radigms: one in which the recorded cell was held at its resting potent ial and one in which synaptic activity was superimposed on a depolariz ing pulse strong enough to evoke four action potentials. In the absenc e of cholinergic modulation, stimulation at 5 Hz induced LTP primarily in the second condition (13.7%, n = 6 out of 9, measured at 10 min af ter tetanus). When stimuli were applied in the presence of the muscari nic agonist carbachol (20 mu M), LTP of greater amplitude was induced in both paradigms (resting: 41.5%, n = 11 out of 16, depolarized: 36%, n = 5 out of 7, measured at 10 min after tetanus). Increases in excit atory postsynaptic potential (EPSP) amplitudes in the presence of carb achol were gradual, starting at the time 5 Hz stimuli were applied and continuing until an action potential was evoked synaptically. in the presence of the NMDA receptor antagonist 2-amino-5-phosphonovaleric ac id (APV), LTP could not be induced. The muscarinic antagonist atropine also prevented LTP induction in the presence of carbachol. Cholinergi c modulation of synaptic plasticity was examined in a previously devel oped realistic biophysical network simulation. In simulations, use of a gradual rate of synaptic modification prevented excessive strengthen ing of synapses, which could cause interference between stored pattern s. The effect of excess synaptic strengthening can be avoided by intro ducing activity dependent depression of synaptic strength. Coactivatio n of learning and depression rules results in a stable system where no interference occurs, at any rate of learning. Implementing the depres sion rule only during recall does not improve the network's performanc e. This implies that reduction in the strength of synaptic connections should occur in the presence of ACh, more than in normal conditions. We propose that two effects of ACh-enhancement of LTP and enhancement of LTD-should act together to increase the stability of the cortical n etwork in the process of acquiring information.