Abstracts

A distinguishing feature of neurogliaform cells is their extremly dense axonal arborization. Moreover, neurogliaform cells are the only known cortical cell type that can reliably activate postsynaptic GABA[sub]A[/sub] and GABA[sub]B[/sub] receptors after discharging a single action potential. Using three-dimensional light microscopic reconstructions and correlated electron microscopic investigations, we found that neurogliaform cells formed synapses (62[plusmn]28 [mu]m) closer to the soma of layer 2/3 pyramidal cells than Martinotti cells (102[plusmn]48 [mu]m) that evoked faster inhibitory responses. Thus, the slow kinetic properties of GABA[sub]A[/sub] responses evoked by neurogliaform cells can not be explained exclusively by the dendritic localization of the synapses. However, there is a twofold difference in unitary axon densities between neurogliaform cells and other interneurons (0.954[plusmn]0.299 and 0.453[plusmn]0.015 [mu]m axon in 1000 [mu]m³).We propose that neurogliaform cells release GABA all over their dense axonal field to activate GABA receptors on dendrites present in the axonal cloud., To test this hypothesis, we studied the physiological properties of responses between neurogliaform cells, other identified interneurons and layer 2/3 pyramidal cells using whole cell patch clamp recording in neocortical slices with the AMPA, NMDA and GABA[sub]B[/sub] receptors blocked., Neurogliaform cells evoked slower GABA[sub]A[/sub] currents (10-90 % rise time: 4.5[plusmn]1.6 ms, weigthed decay time constant: 42[plusmn]9.7 ms, amplitude: 97[plusmn]69 pA) than basket cells (10-90 % rise time: 0.7[plusmn]0.2 ms, weigthed decay time constant: 8.1[plusmn]1.9 ms, amplitude: 130[plusmn]109 pA). The variability in amplitudes of neurogliaform cell-evoked IPSCs (0.14[plusmn]0.04, S.D./mean) was much less than in the basket cell-evoked responses (0.29[plusmn]0.1). Furthermore, gradual changing of extracellular calcium resulted in continuous increases in the amplitude of the responses. Blocking of GABA transporter 1 by NO-711 dramatically increased the decay time constant of neurogliaform cell-evoked IPSCs (by 203[plusmn]110 %) and did not affect basket cell-evoked IPSCs. The low affinity, competitive antagonist of GABA[sub]A[/sub] receptors, TPMPA had a larger effect (58[plusmn]17 %) on the amplitude the neurogliaform cells effect compared to basket cells (35[plusmn]17 %). Alfa1 subunit specific GABA[sub]A [/sub]agonists (zolpidem, Cl218,872) had significant effets on the neurogliaform cell-evoked responses. However, the properties of this modulatory action was different than on basket cell-evoked IPSCs., These results indicate that a spill-over-like mechanism of GABA release takes place following single action potentials in neurogliaform cells, in contrast to the more conventional basket cell synapses. These data suggest that neurogliaform play highly specialized role in regulating neuronal activity in the cortical networks., (Supported by NIH NS35915 to IS [amp] GT; OTKA T049535 and HHMI 55005625 to GT; George E. Hewitt Foundation and Boehringer Fonds to JS.)