The role of the perforant pathway as a trophic factor for neurotransmission in the rat dentate gyrus

Abstract

Changes in electrophysiological function in the hilar associational pathway terminating on dentate granule cells in the rat hippocampal formation were studied following unilateral entorhinal cortex lesions. In rats lesioned as pups (postnatal day 4 [PN 4]) or as adults (PN 60) there was a profound loss of paired-pulse inhibition at 30 days postlesion. Inhibition was unaffected at 10 days postlesion. Entorhinal cortex lesions did not affect population spike amplitude, population excitatory postsynaptic potentials slopes, or long-term potentiation compared to the unlesioned hemisphere. The presence of a complete hippocampal commissurotomy had no effect on excitatory or inhibitory parameters. Laminar analyses of extracellular field potentials from animals lesioned as adults revealed an expansion of functional synapses outward into the dentate molecular layer. This expansion was complete by 10 postlesion days. The changes observed with laminar analyses were not contemporaneous with the changes in paired-pulse inhibition. The loss of inhibition in the hilar associational pathway of entorhinal cortex-lesioned animals thus implies a change in local circuit function rather than an effect from sprouted associational fibers directly onto granule cells. The lack of inhibition in the associational pathway in lesioned animals was not due to a failure of local circuit inhibitory function to develop, since the same findings were obtained when lesions were made neonatally or as adults. Rather, the authors suggest that the present findings arise because of the formation of functional, recurrent, excitatory mossy fiber collateral synapses following entorhinal cortex lesions.