Activation-Dependent Enhancements of Synaptic Strength in Pyriform Cortex Efferents to the Entorhinal Cortex

Abstract

The entorhinal cortex is reciprocally connected with both neocortical sensory areas and the hippocampal formation, and is thought to play a pivotal role in learning and memory. Changes in synaptic strength are thought to provide the major neurophysiological basis for memory formation, but little is known about synaptic plasticity in the entorhinal cortex. The objectives of this research were to provide a basis for the interpretation of evoked potentials recorded from the entorhinal cortex following pyriform (primary olfactory) cortex stimulation 𝘪𝘯 𝘷𝘪𝘷𝘰, and to determine the conditions under which synaptic enhancements in this pathway may occur and contribute to lasting changes in the processing of olfactory information. The synaptic currents which generate field potentials in the entorhinal cortex following pyriform cortex and medial septal stimulation were first localized to the superficial layers of the entorhinal cortex using current source density analysis techniques in the anesthetized rat. This allowed changes in the strength of these synaptic inputs to be monitored in the awake rat by measuring evoked field potential amplitudes at a single cortical depth. Long-term synaptic potentiation (LTP) in this pathway was reliably induced following stimulation of the pyriform cortex with either epileptogenic stimuli, or with prolonged subconvulsive high-frequency trains. Further, stimulation which results in short-term frequency potentiation effects, was found to increase the amount of LTP induced. Concurrent stimulation of the medial septum at a frequency similar to that of the endogenous theta rhythm also resulted in a cooperative enhancement of the LTP produced. Computational modelling techniques were then used to formalize the heterosynaptic contribution of frequency potentiating medial septal inputs to Hebbian synaptic modification in entorhinal cortex. These results indicate that the frequency of rhythmic activity in sensory afferents and the activity of the medial septum may play critical roles in the regulation of synaptic plasticity in the entorhinal cortex.