Actions of excitatory amino acid antagonists on synaptic potentials of layer II/III neurons of the cat's visual cortex

Abstract

Actions of excitatory amino acid (EAA) antagonists on the responses of cells in layers II/III and IV of the cat's visual cortex to stimulation of layer VI and the underlying white matter were studied in slice preparations. Antagonists used were 2-amino-5-phosphonovalerate (APV), a selective antagonist for the N-methyl-D-aspartate (NMDA) type of EAA receptors, and kynurenate, a broad-spectrum antagonist for the three types of EAA receptors. In extracellular recordings it was demonstrated that most of the layer II/III cells were sensitive to APV, while the great majority of the layer IV cells were not. By contrast, kynurenate suppressed the responses completely in both layers. Excitatory post-synaptic potentials (EPSPs) evoked by stimulation of layer VI and the while matter were recorded intracellularly from layer II/III neurons. To determine whether the EPSPs were elicited mono- or polysynaptically, the synaptic delay for each EPSP was calculated from a pair of onset latencies of EPSPs evoked by stimulation of the two sites. Forty-two percent of the layer II/III cells were classified as having monosynaptic EPSPs. In 60% of these monosynaptic cells, the rising slope of the EPSPs was reduced by APV while in the other 40%, it was not. In the former (APV-sensitive cells), subtraction of the APV-sensitive component from the total EPSP indicated that the onset latency of the NMDA receptor-mediated component was roughly equal to that of the non-NMDA component. In the latter (APV-resistant cells), only the slowly-decaying component was in part mediated by NMDA receptors. The conduction velocities of the afferent fibers innervating APV-resistant cells were slower than those of the APV-sensitive cells, suggesting that both types of cells are innervated by different types of afferents. The polysynaptic EPSPs of almost all layer II/III cells were sensitive to APV. The subtraction method indicated that the NMDA component had about the same magnitude as the non-NMDA components. When the slices were superfused by a Mg2+-free solution, the EPSPs were potentiated dramatically, but this potentiation was reduced to the control level during the administration of APV. Similarly, APV-sensitive components were potentiated during the administration of bicuculline, a selective antagonist for gamma-aminobutyric acid receptors of A type. These results suggest that NMDA receptors participate, at varying degrees, in excitatory synaptic transmission at most layer II/III cells in the cat's visual cortex, and their actions appear to be regulated by intracortical inhibition.

Change of conduction velocity by regional myelination yields constant latency irrespective of distance between thalamus and cortex

“…We found that even when we excluded the synaptic delay, the CV WM-IV for ϾP30 (0.31 Ϯ 0.06 m͞s, n ϭ 9) was still Ϸ10-fold smaller than the CV VB-WM (3.28 Ϯ 0.11 m͞s). The calculated synaptic delay for nine cells was 0.61 Ϯ 0.11 ms, which is comparable with the previously reported values for thalamocortical synapses (27)(28)(29).…”

Specific Roles of NMDA and AMPA Receptors in Direction-Selective and Spatial Phase-Selective Responses in Visual Cortex

“…The possibility that inhibition regulates NMDA-mediated activity is consistent with other lines of evidence in area 17 (Artola and Singer, 1987;Shirokawa et al, 1989;Schroeder et al, 1997). The relationship between GABAergic inhibition and NMDA function is probably related to the voltage dependence of NMDA receptors; the binding of extracellular Mg 2ϩ to the channel pore is highly dependent on membrane potential, and changes in the latter could significantly modulate NMDA receptor-mediated activity (for review, see Dingledine, 1999).…”

“…A fundamental difference between layers 2/3 and 4 is the presence in supragranular layers of NMDA receptors, where they have been shown to participate in transmission in vivo (Fox et al, 1989(Fox et al, , 1990 and in vitro (Shirokawa et al, 1989). Our data indicate that AMPA and NMDA receptors both contribute to direction selectivity in supragranular layers (Fig.…”

“…Yet, NMDA receptors in several regions of the adult brain, including the visual pathway, are known to be involved in the transmission of sensory information (Fox et al, 1989;Miller et al, 1989;Sillito et al, 1990;Kwon et al, 1991). Because the two receptor types have different characteristics [importantly, NMDA receptors are sensitive to the membrane potential (for review, see Dingledine, 1999) and to GABAergic inhibition (Artola and Singer, 1987;Shirokawa et al, 1989;Schroeder et al, 1997)], they may have different functional roles in cortical integration. A previous study (Fox et al, 1990) that examined the effect of NMDA receptor blockade in cat area 17 as a function of stimulus contrast found a proportionate reduction of responses at all contrasts.…”

Immunocytochemical Characterization of AMPA-Selective Glutamate Receptor Subunits: Laminar and Compartmental Distribution in Macaque Striate Cortex

“…Similarly, the intense immunostained puncta in layer IVC forms a pattern of alternating intensely stained stripes and poorly stained stripes that can be related to geniculocortical afferent terminations (Hubel and Wiesel, 1972;Hendrickson et al, 1978;DeFelipe and Jones, 1991), clusters of dendrites (Peters and Sethares, 1991), and glutamate immunoreactive processes (Carder and Hendry, 1994). This hypothesis is also supported by a large body of literature indicating that excitatory neurotransmission at thalamocortical synapses is primarily mediated by AMPA receptors (Hagihara et al, 1988;Shirokawa et al, 1989;Fox et al, 1989Fox et al, , 1992Nishigori et al, 1990;Gil and Amitai, 1996). Despite the fact that geniculocortical afferent terminals may represent less than 20% of the asymmetrical synapses in layer IVC (Garey and Powell, 1971;Tigges and Tigges, 1979;Peters et al, 1994), physiological evidence indicates that thalamic input plays an essential role in driving cortical cells (Tanaka, 1983;Ferster et al, 1996).…”