Recurrent Mossy Fiber Pathway in Rat Dentate Gyrus: Synaptic Currents Evoked in Presence and Absence of Seizure-Induced Growth

• Published in: Journal of neurophysiology 1999-04, Vol.81 (4), p.1645-1660
• Main Authors: Okazaki, Maxine M, Molnar, Peter, Nadler, J. Victor
• Format: Article
• Language: English
• Subjects: alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid - pharmacology; Animals; Bicuculline - pharmacology; Dentate Gyrus - cytology; Dentate Gyrus - physiology; Electric Stimulation; Epilepsy, Temporal Lobe - chemically induced; Epilepsy, Temporal Lobe - physiopathology; Excitatory Amino Acid Agonists - pharmacology; Excitatory Postsynaptic Potentials - drug effects; Excitatory Postsynaptic Potentials - physiology; Feedback - physiology; GABA Antagonists - pharmacology; Kainic Acid - pharmacology; Male; Mossy Fibers, Hippocampal - chemistry; Mossy Fibers, Hippocampal - physiology; N-Methylaspartate - pharmacology; Organ Culture Techniques; Parasympathomimetics; Patch-Clamp Techniques; Perforant Pathway - cytology; Perforant Pathway - physiology; Pilocarpine; Rats; Rats, Sprague-Dawley; Receptors, GABA-A - physiology; Receptors, N-Methyl-D-Aspartate - physiology; Staining and Labeling; Status Epilepticus - chemically induced; Status Epilepticus - physiopathology; Synapses - chemistry; Synapses - physiology
• ISSN: 0022-3077; 1522-1598
• DOI: 10.1152/jn.1999.81.4.1645

Department of Pharmacology and Cancer Biology and Department of Neurobiology, Duke University Medical Center, Durham, North Carolina 27710 Okazaki, Maxine M., Péter Molnár, and J. Victor Nadler. Recurrent mossy fiber pathway in rat dentate gyrus: synaptic currents evoked in presence and absence of seizure-induced growth. A common feature of temporal lobe epilepsy and of animal models of epilepsy is the growth of hippocampal mossy fibers into the dentate molecular layer, where at least some of them innervate granule cells. Because the mossy fibers are axons of granule cells, the recurrent mossy fiber pathway provides monosynaptic excitatory feedback to these neurons that could facilitate seizure discharge. We used the pilocarpine model of temporal lobe epilepsy to study the synaptic responses evoked by activating this pathway. Whole cell patch-clamp recording demonstrated that antidromic stimulation of the mossy fibers evoked an excitatory postsynaptic current (EPSC) in ~74% of granule cells from rats that had survived >10 wk after pilocarpine-induced status epilepticus. Recurrent mossy fiber growth was demonstrated with the Timm stain in all instances. In contrast, antidromic stimulation of the mossy fibers evoked an EPSC in only 5% of granule cells studied 4-6 days after status epilepticus, before recurrent mossy fiber growth became detectable. Notably, antidromic mossy fiber stimulation also evoked an EPSC in many granule cells from control rats. Clusters of mossy fiber-like Timm staining normally were present in the inner third of the dentate molecular layer at the level of the hippocampal formation from which slices were prepared, and several considerations suggested that the recorded EPSCs depended mainly on activation of recurrent mossy fibers rather than associational fibers. In both status epilepticus and control groups, the antidromically evoked EPSC was glutamatergic and involved the activation of both AMPA/kainate and N -methyl- D -aspartate (NMDA) receptors. EPSCs recorded in granule cells from rats with recurrent mossy fiber growth differed in three respects from those recorded in control granule cells: they were much more frequently evoked, a number of them were unusually large, and the NMDA component of the response was generally much more prominent. In contrast to the antidromically evoked EPSC, the EPSC evoked by stimulation of the perforant path appeared to be unaffected by a prior episode of status epilepticus. These results support the