Exp Brain Res (1993) 95:271-276 Experimental BrainResearch 9 Springer-Verlag 1993 Component-specific effects of physostigmine on the cat visual evoked potential Kenji Arakawa*, Neal S. Peachey, Gastone G. Celesia, Guido Rubboli** Department of Neurology, Stritch School of Medicine, Loyola University Chicago, 2160 S. First Avenue, Maywood, IL 60153, USA, and Hines VA Hospital, Hines, IL 60141, USA Received: 25 June 1992 / Accepted: 24 February 1993 Abstract. Pattern visual evoked potentials (VEPs) were recorded from the pial surface of the cat primary visual cortex prior to and following the intravenous administra- tion of physostigmine, an agent which blocks the enzyme responsible for the breakdown of synaptically released acetylcholine. The control VEP was composed of a small initial positive deflection (P1), a subsequent large nega- tive wave (N1) and a second large positive wave (P2). Following physostigmine, the amplitude of P1-N1 was diminished whereas that of N1-P2 increased. These ef- fects were long lasting and were blocked by prior treat- ment with scopolamine, a result consistent with media- tion by a muscarinic cholinergic pathway. Waveform subtraction revealed that the physostigmine-sensitive component had a slow, negative polarity waveform while the physostigmine-insensitive component was also slow, but positive in polarity. The fundamental nature of these components remains to be assessed. Nevertheless, the re- sults indicate that waveforms of different polarity com- bine algebraically to yield the conventional VEP. Key words: Acetylcholine - Physostigmine - Visual evoked potential - Cat Introduction The visual evoked potential (VEP) provides a measure of cortical activity and has been widely used in clinical and basic science studies (reviewed by Regan 1989; Brigell and Celesia 1992). Obtained by conventional methods, the VEP comprises several distinct positive- and nega- tive-going waves which are thought to represent the sum- Present address: * Department of Neurology, Neurological Insti- tute, Faculty of Medicine, Kyushu University 60, Fukuoka 812, Japan Present address: ** Department of Neurology, University of Bologna, Bellaria Hospital, Via Altura 3, 1-40131 Bologna, Italy Correspondence to: N.S. Peachey mation of distinct waveforms generated by relatively in- dependent cellular activity (eg., Jeffreys and Axford 1972a,b). In support of this viewpoint, a number of stud- ies have utilized analysis of scalp distribution to dissoci- ate the different VEP components (e.g., Jeffreys and Ax- ford 1972a,b; Lesevre and Joseph 1979; Maier et al. 1987; Ossenblok and Spekreijse 1991). Using a pharmacologi- cal approach, Zemon et al. (1980) dissociated the different components that comprise the VEP. In that study, appli- cation of the GABA blocker bicuculline differentially af- fected the primary positive and negative potentials that comprise the cat VEP. Specifically, bicuculline dimin- ished a late positive potential and enhanced an early neg- ative potential. In addition, depth recordings have been used in awake monkeys to demonstrate that the VEP components originate in different cortical layers (Kraut et al. 1985; Schroeder et al. 1991). Nevertheless, it would be desirable to obtain additional evidence that the differ- ent waves that comprise the VEP are separately generat- ed. In the present study, we provide such evidence based upon our studies of the role of acetylcholine (ACh) in modulating the VEP. Physostigmine, a blocker of acetyl- cholinesterase, selectively diminished a prominent nega- tive wave of the VEP and increased the amplitude of the following positive wave. This observation provides addi- tional evidence that the VEP is comprised of distinct components which overlap temporally but can be sepa- rately affected. Materials and methods Experiments were carried out on 12 adult cats (2.2-3.4 kg). Cats were initially anesthetized with an intraperitoneal injection of pen- tobarbital sodium (35 mg/kg) before tracheal intubation and subse- quent cannulation of the femoral vein and artery. Anesthesia was maintained by intravenous injections of pentobarbital sodium (5 mg/kg/h). Cats were paralyzed with intravenous pancuronium bro- mide (0.04 mg/kg), and were artificially ventilated. The cat's head was fixed in a special stereotaxic frame that allowed unobstructed fields of view. A craniotomy exposed the left cerebral hemisphere. Throughout the experimental session, blood pressure in the femoral artery was monitored by way of a pressure transducer