ELECTROPHYSIOLOGICAL MAPPING OF GABA(A) RECEPTOR-MEDIATED INHIBITION IN ADULT-RAT SOMATOSENSORY CORTEX

1. gamma-Aminobutyric acid-A (GABA(A)) receptor-mediated synaptic curr ents evoked by intracortical stimulation in rat somatosensory cortical slices maintained in vitro were studied using the whole cell patch-cl amp technique. All anatomically identified pyramidal neurons of layer II-III (SG neurons), layer IV (IV neurons), and layer V (IG neurons) g enerated evoked inhibitory postsynaptic currents (eIPSCs) that were bl ocked by bicuculline. At threshold, eIPSCs had kinetic properties (ris e time of 0.9 ms and decay time constant of 9 ms) similar to those of spontaneous IPSCs generated in the same cells. 2. The strength of inhi bition was quantified by determining the stimulus threshold for evokin g responses and the relationship between stimulus strength and eIPSC p eak amplitudes (input/output curve). For eIPSCs recorded in control so lution: the input/output curve was about four times steeper than for e IPSCs recorded in the presence of the ionotropic glutamate receptor an tagonists 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX) and D-2-amino-5- phosphonovalerate (D-AP5), suggesting the dependence of GABA(A) inhibi tion on synpatic excitation of interneurons. 3. In the presence of CNQ X and D-AP5, monosynaptic IPSCs, evoked by stimulation close to the re cording patch pipette, had similar input/output curves in SG and IG ne urons. This suggests that the level of monosynaptic inhibition generat ed in these two populations of cells is similar. 4. When the stimulus was moved to a distant site >350 mu m from the recorded neuron, either in vertical or in horizontal direction, the stimulus intensity requir ed for evoking IPSCs was higher, and the input/output curve was less s teep. This suggests that the density of GABAergic somata and axons pro jecting to the recorded neuron is lower at these distances than at mor e proximal sites. 5. The maximum horizontal distance over which IPSCs could be evoked (''horizontal field'') was larger in layer V than in o ther layers. The horizontal field (distance between stimulating and re cording pipettes) was 600 mu m in layer II-III, 580 mu m in layer IV, and 720 mu m in layer V. Anatomic identification of the somatosensory cortical barrels indicated that the extent of GABAergic projections wa s larger than the barrel hollow and might thus form a substrate for in terbarrel inhibition in layer IV during cross-wisker stimulation. 6. T he maximum vertical inhibitory field was larger than the maximum horiz ontal field. IPSCs could be evoked in layer V neurons by layer I stimu li, showing that a powerful interlaminar inhibition is present that ma y play a role in synchronizing the activity of neurons in a column. IP SCs evoked by layer I stimulation frequently had slower kinetics than those elicited by stimulation at sites close to the soma. 7. These fin dings suggest that functional GABAergic projections are characterized by a large degree of convergence. Quantification of GABA(A)-mediated I PSCs indicates that this zone of inhibitory synaptic convergence onto a given pyramidal neuron is subdivided into a powerful local inhibitor y zone and a surrounding area of long-range, less effective, inhibitor y projections. Potential roles for these concentric inhibitory areas i n cortical processing of sensory information are discussed.