Fundamental differences in spontaneous synaptic inhibition between deep and superficial layers of the rat entorhinal cortex

Abstract

We have previously shown that there are clear differences between spontaneous excitatory synaptic currents recorded in layers V and II of the rat entorhinal cortex (EC) in vitro, and have suggested that these might contribute to a more pronounced susceptibility of the deeper layer to epileptogenesis. In the present study, we have made a detailed comparison of spontaneous synaptic inhibition between the two layers by recording spontaneous inhibitory synaptic currents (sIPSCs) using whole-cell patch-clamp techniques in EC slices. Pharmacological studies indicated that sIPSCs were mediated exclusively by gamma-aminobutyric acid (GABA)(A) receptors. There was little difference in average amplitudes, rise or decay times of sIPSCs in layer II compared with layer V. However, in the former, events occurred at 4-5 times the frequency seen in the latter, and frequencies of </=40 Hz were not uncommon. When activity-independent, miniature IPSCs were isolated in tetrodotoxin (TTX), the frequency in layer V was more than halved, but in layer II only a small reduction was seen, and the frequency remained very high. In terms of kinetics, while averaged sIPSCs in each layer were very similar, detailed comparison of individual sIPSCs within layers revealed distinct differences, possibly reflecting inputs from different subtypes of interneurons or inputs at different somatodendritic locations. In layer V, sIPSCs could be divided into three groups, one with slow rise and decay kinetics and a second with fast rise kinetics, further distinguished into two groups by either fast or slow decay kinetics. The distinction between events in layer II was simpler, one group having both fast rise and decay times and the second with both parameters much slower. Finally, IPSCs could occur in high-frequency bursts in both layers, although these were much more prevalent in layer II. The results are discussed in terms of the overall level of background inhibition in the two layers, as well as how this might relate to their susceptibilities to epileptogenesis.

Recurrent Circuits in Layer II of Medial Entorhinal Cortex in a Model of Temporal Lobe Epilepsy

“…We found similar mediolateral extents of percentage of IPSC-responding sites and average composite IPSC amplitudes in control animals. These findings are consistent with previous reports that layer II stellate cells normally receive strong inhibitory synaptic input (Woodhall et al, 2005).…”

Background Synaptic Activity in Rat Entorhinal Cortex Shows a Progressively Greater Dominance of Inhibition over Excitation from Deep to Superficial Layers

“…In agreement with our studies in L2 and L5 [37] these were largely eliminated (n = 7) by the GABA A -receptor blocker, gabazine (20 µM; Figure 2A). However, the glycine receptor antagonist, strychnine, applied before gabazine (1 µM), also had a weak effect on sIPSCs reducing the frequency by around 10–20% (n = 6) without affecting amplitude (mean IEI 168±117 ms v 198±134 ms Figure 2A).…”

Region-Specific Reduction in Entorhinal Gamma Oscillations and Parvalbumin-Immunoreactive Neurons in Animal Models of Psychiatric Illness

“…Too little is known at present about interneuron subtypes and distribution to suggest different inhibitory circuits in deep and superficial layers. However, it is interesting to note that spontaneous inhibitory events are different in the two layers (Woodhall et al, 2005) and that synaptic plasticity also is expressed differentially (Solger et al, 2004).…”