Disruption of Inhibition in Area CA1 of the Hippocampus in a Rat Model of Temporal Lobe Epilepsy

• Published in: Journal of neurophysiology 2001-11, Vol.86 (5), p.2231-2245
• Main Authors: Denslow, Maria J, Eid, Tore, Du, Fu, Schwarcz, Robert, Lothman, Eric W, Steward, Oswald
• Format: Article
• Language: English
• Subjects: Afferent Pathways - physiopathology; aminooxyacetic acid; Aminooxyacetic Acid - pharmacology; Animals; Dentate Gyrus - physiopathology; Electric Stimulation; Entorhinal Cortex - physiopathology; Epilepsy, Temporal Lobe - physiopathology; Excitatory Postsynaptic Potentials; Hippocampus - drug effects; Hippocampus - pathology; Hippocampus - physiopathology; Kindling, Neurologic; Male; Neural Inhibition; Neurotoxins - pharmacology; Perforant Pathway - physiopathology; Rats; Rats, Sprague-Dawley
• ISSN: 0022-3077; 1522-1598
• DOI: 10.1152/jn.2001.86.5.2231

  1 Department of Neuroscience,   2 Department of Neurology, and   3 Department of Neurosurgery, University of Virginia Health Sciences Center, Charlottesville, Virginia 22908; and   4 Maryland Psychiatric Research Center, University of Maryland School of Medicine, Baltimore, Maryland 21228 Denslow, Maria J., Tore Eid, Fu Du, Robert Schwarcz, Eric W. Lothman, and Oswald Steward. Disruption of Inhibition in Area CA1 of the Hippocampus in a Rat Model of Temporal Lobe Epilepsy. J. Neurophysiol. 86: 2231-2245, 2001. Previous studies have revealed a loss of neurons in layer III of the entorhinal cortex (EC) in patients with temporal lobe epilepsy. These neurons project to the hippocampus and may activate inhibitory interneurons, so that their loss could disrupt inhibitory function in the hippocampus. The present study evaluates this hypothesis in a rat model in which layer III neurons were selectively destroyed by focal injections of the indirect excitotoxin, aminooxyacetic acid (AOAA). Inhibitory function in the hippocampus was assessed by evaluating the discharge of CA1 neurons in response to stimulation of afferent pathways in vivo. In control animals, stimulation of the temporo-ammonic pathway leads to heterosynaptic inhibition of population spikes generated by subsequent stimulation of the commissural projection to CA1. This heterosynaptic inhibition was substantially reduced in animals that had received AOAA injections 1 mo previously. Stimulation of the commissural projection also elicited multiple population spikes in CA1 in AOAA-injected animals, and homosynaptic inhibition in response to paired-pulse stimulation of the commissural projection was dramatically diminished. These results suggest a disruption of inhibitory function in CA1 in AOAA-injected animals. To determine whether the disruption of inhibition occurred selectively in CA1, we assessed paired-pulse inhibition in the dentate gyrus. Both homosynaptic inhibition generated by paired-pulse stimulation of the perforant path, and heterosynaptic inhibition produced by activation of the commissural projection to the dentate gyrus appeared largely comparable in AOAA-injected and control animals; thus abnormalities in inhibitory function following AOAA injections occurred relatively selectively in CA1. Electrolytic lesions of the EC did not cause the same loss of inhibition as seen in animals with AOAA injections, indicating that the loss of inhibition in CA1 is not due to the loss of excitatory dri