248 BRES 16581 Brain Research, 548 (1991) ~ ' ~5 ~, © 1991 Elsevier Science Publishers B.V. 0006-8993/91/$03,5li ADONIS 0006899391165~1B Selective suppression of afferent but not intrinsic fiber synaptic transmission by 2-amino-4-phosphonobutyric acid lAP4) in piriform cortex Michael E. Hasselmo and James M. Bower Division of Biology, California Institute of Technology, Pasadena, CA 91125 (U.S.A.) (Accepted 4 December 1990) Key words: Presynaptic; Glutamine; Olfactory; Lamination; Paired-pulse facilitation Differences in the glutaminergic modulation of afferent and intrinsic fiber synaptic transmission in piriform (olfactory) cortex were investigated using extracellular and intraceilular recording techniques in a transverse slice preparation. 2-Amino-4-phosphonobutyricacid lAP4) strongly suppressed synaptic potentials evoked by afferent fiber stimulation in layer 1 a, while having a much weaker effect on synaptic potentials evoked by intrinsic fiber stimulation in layer lb. Both the racemic mixture and L-(+)-enantiomer of AP4 showed this differential effect. Suppression of afferent fiber synaptic potentials was accompanied by an increase in paired pulse facilitation, suggesting a pre-synaptic mechanism, while intrinsic fiber synaptic potentials showed little change in facilitation. Previous work has shown that cholinergic modulation in piriform cortex appears selective for intrinsic fiber synapses. The present data describes a pre-synaptic glutaminergic modulation complementary to the cholinergic modulation. INTRODUCTION The primary olfactory cortex, or piriform cortex, shows a distinct laminar segregation of synaptic input to the apical dendrites of its principal neurons 11'3°'34. Af- ferent fibers from the lateral olfactory tract (LOT) terminate on distal portions of pyramidal cell dendrites, while intrinsic and association fibers terminate on prox- imal portions of these same dendrites 11'3°'34. Interest- ingly, a laminar segregation of synaptic input to the apical principal cell dendrite appears in all three regions of the hippocampus 21'35'39. The consistent appearance of this clear laminar segregation suggests it has some functional significance. A possible role of the laminar segregation of piriform cortex fiber systems is to segregate the neurochemical modulation of different fiber systems. Previously, re- search in slice preparations of piriform cortex has shown that the glutamic acid analogue 2-amino-4-phosphono- butyric acid lAP4) suppresses piriform cortex field potentials and unit activity evoked by stimulation of the lateral olfactory tract 1"5"2°'22"23, acting by an apparent presynaptic mechanism 1. Preliminary evidence from transverse slices suggests this effect is specific to afferent fiber synapses 23. More recently, we have discovered a form of pharmacological modulation which appears specific to intrinsic fiber synapses 17'18. The acetylcholine analogue carbachol strongly suppresses intrinsic fiber synaptic responses, while leaving afferent fiber synaptic responses unaffected. In the experiments described here, we provide detailed evidence that AP4 has a comple- mentary effect to carbachol, strongly suppressing afferent fiber synaptic responses, while having a far weaker effect on intrinsic fiber synaptic responses. MATERIALS AND METHODS Slice preparation Extracellular and intracellular recordings were obtained from brain slice preparations of piriform cortex taken from 17 albino Sprague-Dawtey rats. Brains removed from rats anesthetized with ether were mounted in a cooled bathing medium (see below) and sliced on a vibratome lOTS 3000M). Slices were made transverse to the laminar organization of the cortex. Slices 350-b~m-thick were taken, starting 0.5 mm rostral to the anterior commissure and proceeding approximately 2.45 mm caudally. Prior to recording, slices were maintained at room temperature for a rmnimum of 2 h in vials bubbled with 95% 02 and 5% CO2 containing the following water-based solution (in mM): NaHCO3 26, NaCI 124. KCi 5, KH2PO 4 1.2, CaC! 2 2.4, MgSO4 1.3. and glucose 10. The same solution was also used for perfusion of the slice chamber. For recording, the slice was mounted on a nylon grid in a standard submersion-type slice chamber, with temperature maintained at 37 °C with an American Hamilton temperature eontroUer. Super- fusion of bathing medium at approximately 5 ml/min, was main- tained using stopcocks and an isometric pump on the outflow tube. Slices were transilluminated, which allowed visually guided place- Correspondence: M. Hasselmo, Dept. of Psychology, Harvard University, 33 Kirkland St., Cambridge, MA 02138, U.S.A.