ABSTRACT
Functional and molecular changes in glutamate transporters during kindling epileptogenesis were investigated in hippocampus CA1-region of rats. In control animals total glutamate transporter activity was indicated by the stimulatory effect of the high-affinity transporter blocker L-trans-pyrrolidine-2,4-dicarboxylate on extracellular glutamate and aspartate concentrations, as measured by in vivo microdialysis. This blocker-induced elevation was absent already early during epileptogenesis. CA1 levels of the glutamate transporter subtypes GLAST and GLT-1, analyzed by quantitative immunoblotting, did not change during kindling epileptogenesis. However, the 60% decrease in EAAC-1 level observed in age-matched controls was fully compensated for in kindled animals 4-5 weeks after the last generalized seizure. These results indicate a compensatory change of the neuronal EAAC-1 glutamate transporter in CA1 region during kindling epileptogenesis, which may be the consequence of a decrease in total transporter activity.
Subject(s)
Adaptation, Physiological , Carrier Proteins/metabolism , Epilepsy/etiology , Hippocampus/metabolism , Kindling, Neurologic , Symporters , ATP-Binding Cassette Transporters/metabolism , Amino Acid Transport System X-AG , Animals , Aspartic Acid/metabolism , Dicarboxylic Acids/pharmacology , Excitatory Amino Acid Transporter 1 , Excitatory Amino Acid Transporter 3 , Extracellular Space/metabolism , Glutamate Plasma Membrane Transport Proteins , Glutamic Acid/metabolism , Immunoblotting , Microdialysis , Pyrrolidines/pharmacology , Rats , Rats, WistarABSTRACT
The possibility of a direct projection from the perirhinal cortex (PER) to areas CA1 and subiculum (SUB) in the hippocampus has been suggested on the basis of tracer studies, but this projection has not unequivocally been supported by physiological studies. The demonstration of such a functional pathway might be important to understand the functioning of the hippocampal memory system. Here we present physiological and further anatomical evidence for such a connection between PER and the hippocampus. Electrical stimulation of PER in vivo evoked field potentials (EFPs) at the border area of CA1/SUB, consisting of a short latency and a longer latency component. Current source density analysis revealed that the sink of the short latency component was situated in the molecular layer of area CA1/SUB, while the longer latency component had its sink in the outer molecular layer of the dentate gyrus (DG). Anterograde tracer injections in PER showed labelled fibres in the border area of CA1/SUB, but anatomical evidence for a projection of PER to DG was not found. When synaptic transmission in the entorhinal cortex was partly blocked, the amplitude of the longer latency component of the recorded EFPs in the hippocampus was decreased while the short latency component was not affected, which suggests that the indirect pathway originating in PER is mediated through a synaptic relay in the entorhinal cortex. From the present results we conclude that information originating in PER reaches area CA1/SUB by parallel, direct and indirect, routes. The existence of this parallel organization appears to form an essential feature for the proper function of the medial temporal lobe memory system.
