Behavioural Brain Research 133 (2002) 45 – 56 Research report Metabotropic glutamate receptors in the hippocampus and nucleus accumbens are involved in generating seizure-induced hippocampal gamma waves and behavioral hyperactivity Jingyi Ma, L. Stan Leung * Departments of Physiology and Clinical Neurological Sciences, London Health Sciences Centre, Uniersity Campus, The Uniersity of Western Ontario, London, Canada N6A 5A5 Received 5 September 2001; received in revised form 22 October 2001; accepted 22 October 2001 Abstract The involvement of metabotropic glutamate receptor (mGluR) subtypes in the generation of hippocampal EEG (30 – 100 Hz) and behaviors induced by a hippocampal afterdischarge (AD) was examined in freely behaving rats. A hippocampal AD induced an increase in gamma waves (30 – 100 Hz) for 20 min, accompanied by behavioral hyperactivity. Bilateral intracerebroventricular (i.c.v.) infusion of (RS )--methyl-4-carboxyphenylglycine (MCPG), a group I and II mGluR antagonist, 30 min before a hippocampal AD, significantly suppressed both the increase in gamma waves and the behavioral hyperactivity. The hippocampal theta rhythm, the spontaneous hippocampal gamma waves, and evoked field potential oscillations of 40 Hz were not affected by MCPG. Pre-infusion (i.c.v.) of (2S )--ethylglutamic acid (EGLU; a group II mGluR antagonist), but not (RS )-1-aminoindan- 1,5-dicarboxylic acid (AIDA; a group I mGluR antagonist), suppressed the postictal increase of both hippocampal gamma waves and behaviors. MCPG was infused locally into different brain structures in order to specify its target sites. Intra-hippocampal infusion of MCPG, or EGLU, blocked the increase in both gamma waves and behaviors. Infusion of MCPG into the nucleus accumbens suppressed the postictal behavioral hyperactivity without affecting the increase in hippocampal gamma waves. MCPG injected into the medial septum blocked neither postictal gamma activity nor behavioral hyperactivity. It is suggested that the group II mGluRs in the hippocampus are involved in generation of the postictal hippocampal gamma waves, while behavioral hyperactivity is partly mediated by mGluRs in the nucleus accumbens. However, spontaneous gamma and theta waves in the normal hippocampus are not mediated by mGluRs. © 2002 Elsevier Science B.V. All rights reserved. Keywords: Hippocampus; Nucleus accumbens; Gamma waves; Theta rhythm; mGluR; Temporal lobe seizures; Postictal behavior www.elsevier.com/locate/bbr 1. Introduction There has been intense interest in neural oscillations of frequency 30–100 Hz, otherwise known as gamma oscillations. In various sensory structures, gamma rhythm has been proposed to be involved in perception or sensory binding [23,63]. In the hippocam- pus, the function of the gamma rhythm is not clear. Hippocampal gamma rhythm is known to increase with behavioral activation, in parallel with a theta rhythm [14,35]. Lisman and Idiart [41] proposed that hippocampal gamma oscillations may serve a mnemonic function. The characteristics of hippocampal gamma waves vary greatly across different preparations. In the rat, the spontaneous gamma activity is synchronous across large areas of the hippocampus, and presumably inde- pendently generated by CA3/CA1, hilar and entorhinal cortical neurons [11,14,39,56]. In behaving rats, gamma activity in CA1 is increased following a hippocampal afterdischarge (AD) [33,42]; lasting upwards for 20 min and accompanied by behavioral hyperactivity [33,42]. * Corresponding author. Tel.: +1-519-663-3733; fax: +1-519-663- 3753. E-mail address: sleung@uwo.ca (L.S. Leung). 0166-4328/02/$ - see front matter © 2002 Elsevier Science B.V. All rights reserved. PII:S0166-4328(01)00445-4