Putative Amino Acid Transmitters in the Amygdala

Abstract

The amygdala is involved in temporal lobe seizures, in man as well as in animal models (refs. in Ben-Ari, 1981), and is among the brain structures from which epileptiform seizures can be most effectively elicited by repeated electrical stimulation (Racine, 1981) or by topical injections of neuroexcitants (Ben-Ari et al., 1980; Tremblay et al., 1983). A better understanding of how the amygdala participates in these epileptic phenomena requires, among other things, more insight into its transmitter mechanisms. The amino acid transmitters gamma-aminobutyrate (GABA), glutamate (Glu), and aspartate (Asp) are of particular interest in this respect since it is assumed that they play decisive roles in the pathogenesis and sequelae of epilepsy (Meldrum, 1984). It is now time for increased efforts to unravel the amino acid transmitter mechanisms in the amygdala. First, the efferent and afferent fiber systems of the various amygdaloid subdivisions have recently been mapped in considerable detail (refs. in Ben-Ari, 1981), facilitating the undertaking and interpretation of experiments aimed at tracing transmitter-specific pathways. Second, new methods have been introduced to supplement those based on autoradiography of in vitro high affinity uptake of radiolabeled amino acids or on immunocytochemistry of glutamic acid decarboxylase (GAD), which have hitherto been the predominant histological techniques in amino acid transmitter research (for references see 9ttersen and Storm-Mathisen, 1984a). Thus, evidence has accumulated that D-[³H]Asp and [³H]GABA, injected in vivo, are selectively transported in axons of Glu/Asp-ergic and GABA-ergic neurons, respectively, leading to labeling of the parent cell bodies (Streit, 1980). Further, we have developed immunocytochemical techniques for the demonstration of GABA, Glu, and Asp, using antisera raised against the amino acids conjugated to protein by glutaraldehyde (Storm-Mathisen et al., 1983, 1986; Ottersen and Storm-Mathisen, 1984a,b, 1985; Storm-Mathisen and Ottersen, 1986). Antisera have also been raised against conjugates of taurine (Tau; Madsen et al., 1985; Ottersen et al., 1985), which is a more equivocal transmitter candidate than GABA, Glu, and Asp. In the present paper we report data obtained with amino acid immunocytochemistry and autoradiography of amino acid uptake and transport. Some of the results have been published elsewhere (Fischer et al., 1982; Ottersen and Storm-Mathisen, 1984a; Storm-Mathisen and Ottersen, 1986).