BACKWARD SIGNAL FROM MEDIAL TEMPORAL-LOBE IN NEURAL CIRCUIT REORGANIZATION OF PRIMATE INFEROTEMPORAL CORTEX

Neuropsychological theories proposed a critical role of the interactio n between the medial temporal lobe and neocortex, in the formation of long-term memory for facts and events, which has often been tested by learning of a series of paired words or figures in humans. We identify neural mechanisms of this long-term memory formation process by singl e-unit recording and molecular biological methods in an animal model o f visual pair-association task in monkeys. In our previous studies, we found a group of neurons that manifested selective responses to both of the paired associates (pair-coding neuron) in the anterior inferior temporal (IT) cortex. It provides strong evidence that single IT neur ons acquire the response-selectivity through associative learning, and suggests that the reorganized neural circuits for the pail-coding neu rons serve as the memory engram of the pair-association learning. In t his article, we investigated further mechanisms of the neural circuit reorganization. First, we tested the role of the backward connections from the medial temporal lobe to IT cortex. Ibotenic acid was injected unilaterally into the entorhinal and perirhinal cortex which provided massive backward projections ipsilaterally to IT cortex. We found tha t the limbic lesion disrupted the associative code of the IT neurons b etween the paired associates, without impairing the visual response to each stimulus. Second, we ask why the limbic-neocortical interactions are so important. We hypothesize that limbic neurons would undergo ra pid modification of synaptic connectivity and provide backward signals that guide reorganization of neocortical neural circuits. We then inv estigated the molecular basis of such rapid synaptic modifiability by detecting the expression of immediate-early genes. We found strong exp ression of zif268 during the learning of a new set of paired associate s, most intensively in area 36 of the perirhinal cortex. All these res ults with visual pair-association task support our hypothesis, and dem onstrate that the 'consolidation' process, which was first Proposed on the basis of clinico-psychological evidence, can now be examined in t he primate with neurophysiolocical and molecularbiological approaches. ((C) Academie des sciences/Elsevier, Paris.)