DIFFERENCES IN STRIATAL SPINY NEURON ACTION POTENTIALS BETWEEN THE SPONTANEOUSLY HYPERTENSIVE AND WISTAR-KYOTO RAT STRAINS T. L. PITCHER, J. R. WICKENS AND J. N. J. REYNOLDS* Basal Ganglia Research Group, Department of Anatomy and Struc- tural Biology, School of Medical Sciences, University of Otago, PO Box 913, Dunedin 9054, New Zealand Abstract—The spontaneously hypertensive rat (SHR) and the Wistar-Kyoto (WKY) inbred rat strains display behavioral dif- ferences characterized by relative increases and decreases in levels of activity. Both strains have subsequently been utilized as animal models of hyperactive and hypoactive be- havioral traits. The etiology of these behavioral characteris- tics is poorly understood, but may stem from alterations in the physiology of selected neural circuits or catecholamine systems. This study investigated the cellular properties of neurons from three genetically related strains: the SHR; WKY; and Wistar (WI). In vivo intracellular recordings were made under urethane anesthesia from spiny projection neu- rons in the striatum, a brain area involved in behavioral acti- vation. Results obtained from 71 spiny projection neurons indicate that most cellular properties of these neurons were very similar across the three strains. However, the amplitude and half-duration of both spontaneously occurring and cur- rent-evoked action potentials were found to be significantly different between the SHR and WKY strains with neurons from the SHR firing action potentials of relatively greater amplitude and shorter duration. Action potential parameters measured from the WI rats were intermediate between the two other strains. These differences in action potentials be- tween two behaviorally distinct strains may reflect altered functioning of particular membrane conductances. © 2007 IBRO. Published by Elsevier Ltd. All rights reserved. Key words: SHR, WKY, striatum, urethane-anesthetized, in- tracellular recording. The spontaneously hypertensive rat (SHR) was developed as an inbred strain to model aspects of human hyperten- sion (Okamoto et al., 1972). During the selective breeding for high blood pressure, a number of behavioral character- istics were also fixed in the SHR genome. Some of these behavioral characteristics resemble those displayed in at- tention deficit hyperactivity disorder (ADHD) (Sagvolden et al., 1993, 1998). Interestingly, another genetically related strain, the Wistar-Kyoto (WKY) also displays abnormal behaviors and has subsequently been proposed as a model of depression (Pare, 1994; Malkesman et al., 2006). These strains are generally described as being hyperac- tive (SHR) and hypoactive (WKY), thus being at the oppo- site ends of the behavioral continuum. The etiology of these behavioral anomalies is not known. However, some characteristics may be explained by alterations in dopamine functioning within the CNS (Viggiano et al., 2003). Alterations have been reported in both the SHR and WKY dopaminergic systems (Kujirai et al., 1990; Linthorst et al., 1991; Kirouac and Ganguly, 1993; Russell et al., 1995; Watanabe et al., 1997; Jiao et al., 2003; Mill et al., 2005). Whether a direct consequence of this altered dopamine function or not, differences in the physiology of brain areas involved in generating behavioral output could underlie the behavioral differences reported in these strains. The basal ganglia is a neural circuit intimately involved in motor activity. The input nucleus of the basal ganglia, the striatum (caudate nucleus and putamen) receives ex- tensive inputs from widespread areas of the cortex (Mc- George and Faull, 1989). Cortical information is processed in the striatum and output signals are sent via the spiny projection neurons to either the globus pallidus external segment (indirect pathway) or the globus pallidus internal segment (entopeduncular nucleus in rodents) or substantia nigra pars reticulata (direct pathway). Information is then relayed through the thalamus to the motor areas of the cor- tex. Information processing in the striatum is important for selection and initiation of motor sequences. Disruption of the striatal circuits, such as after the loss of dopaminergic inputs in Parkinson’s disease or degeneration of striatal neurons in Huntington’s disease, results in disorders dominated by mo- tor abnormalities. Thus, variation in normal spiny projection neuron activity, mediated by alterations in cellular properties may also affect information flow through the basal ganglia and therefore, motor activity. The present study utilized in vivo intracellular recording techniques to investigate the cellular properties of striatal spiny projection neurons in three rat strains: the SHR, a commonly used model of ADHD-like behaviors; the WKY, the normotensive genetic control for SHR and the standard albino Wistar (WI) strain. The purpose of the study was to investigate if there were, at the cellular level, physiological correlates to behavior. EXPERIMENTAL PROCEDURES Experimental subjects Animals from the SHR, WKY and WI strains were obtained from the University of Otago Animal Facility (Dunedin, New Zealand). *Corresponding author. Tel: +64-3-4795781; fax: +64-3-4797254. E-mail address: john.reynolds@stonebow.otago.ac.nz (J. N. J. Reyn- olds). Abbreviations: ADHD, attention deficit hyperactivity disorder; AHP, afterhyperpolarization; ANOVA, analysis of variance; SHR, spontane- ously hypertensive rat; WI, Wistar; WKY, Wistar-Kyoto. Neuroscience 146 (2007) 135–142 0306-4522/07$30.00+0.00 © 2007 IBRO. Published by Elsevier Ltd. All rights reserved. doi:10.1016/j.neuroscience.2007.01.003 135