1. The horizontal propagation of epileptiform discharges has been studied in slices of neocortex treated with high concentrations of bicuculline methiodide, an antagonist of the inhibitory transmitter gamma-aminobutyric acid (GABA). The cortical areas examined were: primary somatosensory (SmI) and motor (MI), and primary (area 17) and secondary (area 18) visual areas of rats, and area 17 of cats. In all of these areas an electrical stimulus evoked single, all-or-none paroxysmal field potentials (PFPs) that propagated across the entire width of the slice without decrement. 2. The velocity of PFP propagation was approximately 0.06-0.09 m/s when averaged over cortical distances of several millimeters. PFP propagation occurred equally well in both directions across a slice. 3. Measurement of PFP propagation at higher spatial resolution (100-180 micron intervals) revealed that velocity was not homogeneous within rat SmI, rat area 18 and cat area 17, but instead varied manyfold as horizontal position changed. In these areas of cortex, propagation patterns were spatially periodic; power spectra reveal that the dominant spatial frequencies were centered about 1 mm-1, with negligible contributions above 2 mm-1. Occasionally PFP propagation was discontinuous, skipping over a small region of cortex and arriving distally before propagating into the more proximal region. 4. In those cortices with periodic propagation patterns, PFP velocity was also strongly direction-dependent. Propagation patterns measured in opposite directions across the same strip of cortex displayed similar periodicities, but in many slices they were negatively correlated, i.e., the propagation pattern in one direction was antiphasic compared to that in the other direction. 5. In contrast, propagation velocity across the center of area 17 of the rat was relatively constant and not directional. Near the boundaries of areas 17 and 18, however, PFP velocity changed abruptly and became periodic within area 18. Similarly, velocity within rat MI was more constant and less directional than in the adjacent SmI. 6. The patterns of PFP propagation velocity are often spatially periodic, directionally asymmetric, and depend upon cortical area. We suggest that the periodic patterns reflect systematic variations in the length or density of horizontal excitatory connections. Alternatively, or concurrently, periodicities could arise from the patchy distributions of intrinsic connections that have been observed anatomically in many areas of neocortex.

The binding affinities of four hallucinogenic agents were analyzed at nine neurotransmitter binding sites in human cortex. d-Lysergic acid diethylamide (d-LSD), N,N-dimethyltryptamine (DMT), 1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane (DOI) and 1-(2,5-dimethoxy-4-bromophenyl)-2-aminopropane (DOB) display highest affinity for the recently identified "DOB binding site" labeled by 77Br-R(-)DOB. The phenalkylamines, DOI and DOB, display subnanomolar affinity for the 77Br-R(-)DOB-labeled site, whereas the indolealkylamines, d-LSD and DMT, display nanomolar affinity for this site. d-LSD was the most potent of the four hallucinogens at six of the other eight sites analyzed in this study. All four hallucinogens also display high affinity for the 5-hydroxytryptamine2 (5-HT2) receptor subtype, with potencies ranging from 4 to 360 nM. Marked differences in relative affinities were observed between the indolealkylamines and the phenalkylamines at the 5-HT1A, 5-HT1D, and DOB binding sites. These rank-order differences in affinities are likely to account for the differing effects of these agents in various biochemical and physiological assays.

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