Different reactions of control and epileptic rats to administration of APV or muscimol on thalamic or CA3-induced CA1 responses.
The physiology and pharmacology of CA1 is changed in epilepsy. There is evidence that the thalamic input to CA1 has a somewhat different physiological effect compared with the CA3 input. In this study we sought to determine whether this difference in physiology persists in epilepsy, and whether there are changes in the pharmacologic profile of these responses. Under urethane two stimulating electrodes were placed in mid to ventral CA3 and in the midline thalamus of control or epileptic rats. One glass micropipette electrode was placed into CA1 for recording. After the baseline acquisition of CA1-evoked responses to single- or paired-pulse stimulation, the stimuli were repeated with local application of either the GABAA agonist muscimol or the NMDA antagonist dl-2-amino-5-phosphonovalerate (APV). The CA1 response of epileptic rats had a smaller population postsynaptic potential (PSP) and spike amplitudes, longer PSP duration, multiple spikes, and the paired-pulse (at 20-ms intervals) facilitation in contrast to the paired-pulse depression seen in control and kindled rats. The duration of the PSP as well as the amplitude and number of spikes were reduced by administration of APV or muscimol into CA1 in both control and epileptic rats. In control rats, APV enhanced the depression induced by maximal paired thalamic or CA3 stimulation at 20-ms intervals and reduced the facilitation of threshold stimulation into no change. In contrast, muscimol in control rats reversed the depression induced by paired maximal stimulation into a mild facilitation and reduced the facilitation of threshold stimulation. In epileptic rats neither APV nor muscimol had a significant effect on the changes of the CA1 responses induced by maximal or threshold paired stimulation. This initial in vivo study demonstrated that the physiology and pharmacology of CA1 in epileptic rats are different from control rats. Although there are physiological differences in the evoked responses that are linked to the site of stimulation in the control and epileptic group, the pharmacology in each condition is independent of the site of stimulation.
Zhang
De Xing
DX
Department of Neurology, University of Virginia Health Sciences Center, Charlottesville, Virginia 22908, USA.
Bertram
E H
EH
D015763:2-Amino-5-phosphonovalerate / Q000494:pharmacology*; D000200:Action Potentials / Q000187:drug effects* / Q000502:physiology; D000818:Animals; D004827:Epilepsy / Q000503:physiopathology*; D008297:Male; D009118:Muscimol / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013788:Thalamus / Q000187:drug effects* / Q000502:physiology
D009118:Muscimol; D015763:2-Amino-5-phosphonovalerate