Lesions of the medial or lateral perforant path have different effects on hippocampal contributions to place learning and on fear conditioning to context

The axons of the neurons in the medial and lateral components of the entorh inal cortex (MEC and LEG) form the medial and lateral perforant paths (MPP and LPP) which represent the major source of cortical input to the hippocam pus. Anatomical, physiological, and pharmacological studies have shown that MPP and LPP are distinct. Unfortunately. assessment of the functional sign ificance of damage to either of these pathways has not used tasks known to be sensitive to hippocampal function in the rodent. In this study, we perfo rmed dissociated lesions of MPP and LPP using a combined physiological and anatomical method. Rats with lesions of either the MPP or the LPP were test ed on place learning in the water task and on a discriminative fear conditi oning to context task. The results indicated that the MPP, but not LPP, les ions resulted in impaired place learning. The context discrimination data r evealed an amygdala-like, reduced fear effect of MPP lesions and an enhance d discriminative fear conditioning to context effect of LPP lesions. Consis tent with a two-stage model of spatial learning proposed by Buzsaki (Buzsak i G, Two-stage model of memory trace formation: a role for 'noisy' brain st ates, Neuroscience 1959;31(3):551-570), the impairment in the water task ca n be interpreted as reflecting the higher efficiency of the MPP synapses in activating hippocampal neurons. The context discrimination results can be explained by either a dissociation of sensory information that reaches the MEC and LEG, of alternatively, by a dissociation between the limbic nature of the MEC and the sensory nature of the LEG. (C) 1999 Elsevier Science B.V . All rights reserved.