Quantitative effects of GABA and bicuculline methiodide on receptive field properties of neurons in real and simulated whisker barrels

1. Carbon fiber multibarrel glass microelectrodes were used to record extracellular single-unit activity during microiontophoretic application of gamma-aminobutyric acid ( GAB A) or bicuculline methiodide (BMI) onto layer IV barrel neurons in the somatosensory cortex of fentanyl-sedated rats. Excitatory and inhibitory aspects of the neurons' receptive fields were quantified with the use of controlled whisker stimuli. The principally activating whisker and one of its immediately adjacent neighbors were deflected alone or in paired combinations involving a condition-test paradigm. 2. Units were distinguished electrophysiologically on the basis of the time course of their action potential waveforms. Data were obtained from 26 regular-spike units (RSUs; presumed spiny stellate cells) and 7 fast-spike units (FSUs; presumed GABAergic neurons). An average of 15.0 nA of GABA produced a one-third to one-half reduction in RSU responses evoked by the maximally effective stimulus. An average of 8.7 nA of BMI was needed to counteract this reduction. This amount of BMI, in the absence of exogenous GABA, was found to increase average RSU and FSU responses by 98 and 53%, respectively, relative to predrug levels. 3. For RSUs, the BMI-induced twofold increase in responses evoked by moving the principal whisker at the neuron's best deflection angle was accompanied by an almost threefold increase in responses evoked by similarly moving an adjacent whisker. Disproportionately large percentage increases were also seen for responses to nonpreferred directions of principal and adjacent whisker movement. BMI thus effectively increased receptive field size and decreased angular tuning. Similarly, responses to stimulus offsets, which are normally smaller than ON responses, were increased proportionally more. 4. Predrug responses of FSUs were more vigorous than those of RSUs. However, FSUs showed a similar inverse relationship between percentage increase with BMI and initial response magnitude, although the proportional increases were less pronounced. 5. GABA, like BMI, had the greatest proportional effects on those responses that were initially smallest. It produced results opposite those of BMI, effectively decreasing receptive field size and sharpening angular tuning. 6. A previously described computational model of a barrel was tested for its ability to reproduce quantitatively the effects of BMI and GABA. The application of BMI was simulated by decreasing the strength of the inhibitory inputs onto the particular cell under study in the model network. GABA microiontophoresis was simulated by adding a constant hyperpolarizing voltage. The model RSUs and FSUs displayed proportional changes in response magnitude that were quantitatively similar to those of their biological counterparts. 7. Surround inhibition was greatly attenuated by BMI application, both for the real and simulated barrel neurons. Disinhibition was less pronounced for the former, perhaps because, unlike the simulated neurons, they also possess GABA(B) receptors, which are unaffected by BMI. 8. We conclude that the inhibitory receptive field properties of barrel neurons can be explained by intrabarrel inhibition and that the expansion of receptive field size and loss of angular tuning with BMI is due to an enhanced effectiveness of convergent, multi-whisker thalamocortical input. Examination of the model neurons' behavior suggests that the altered activity in response to GABA or BMI application, respectively, can be explained by the nonlinear effects of shifting somal membrane potential away from or toward the neuron's firing threshold.