AMINO-ACIDS MODIFY THALAMOCORTICAL RESPONSE TRANSFORMATION EXPRESSED BY NEURONS OF THE VENTROBASAL COMPLEX

The hypothesis has been tested that inhibitory mechanisms, active spatially and temporally between the input and the output of thalamic neurons, determine the nature of the information transmitted to the cerebral cortex. To enable this assessment, in barbiturate-anesthetized cats and urethane-anesthetized rats juxtacellular recordings were performed together with microiontophoretic ejection of transmitter agonists and antagonists. The effects of these drugs were studied on responses evoked by mechanical stimulation of cutaneous receptive fields (RFs) of neurons in the thalamic ventrobasal complex (VB). Neurons from different parts of the VB were investigated: 29 units were located medially, in the ventral posteromedial nucleus (VPM; facial RFs), and 11 units were located laterally, in the ventral posterolateral nucleus (VPL; forepaw and body RFs). A further eleven VB units had no detectable RF. Twenty-six neurons were tested with electrical stimulation of the somatosensory cortex (SI), 17 of these being identified as thalamo-cortical relay neurons and 5 being classified as presumed interneurons; the remaining 4 could not be activated. Four additional recordings were from trigemino-thalamic or thalamo-cortical fibers. For the quantitative assessment of the neurons' input and output, neuronal activity was induced by feedback-controlled, mechanical trapezoidal and/or sinusoidal stimuli applied to sinus hairs, fur or skin and the numbers of prepotentials and soma spikes were compared in peristimulus time histograms (PSTHs) generated simultaneously for both types of signal from 'DC' recordings. Iontophoretic administration of excitatory amino acids (EAAs) or bicuculline methiodide (BMI) increased output-input ratios in 87% of the cases tested, due to a higher rate of conversion of prepotentials into soma spikes taking place. In cases of neurons exhibiting a sustained-to-transient response pattern, changes to sustained-to-sustained patterns were demonstrated. Tests with gammaaminobutyric acid (GABA) produced decreased output-input ratios in 90% of the neurons, due to a lower conversion rate of prepotentials into soma spikes taking place. In cases of neurons exhibiting high output-input ratios (sustained-to-sustained type), the responses changed to the sustained-to-transient pattern. For cortically evoked antidromic spikes of VB neurons, GABA produced a failure of the initial segment (IS-) spike to invade the soma, whereas BMI and glutamate (Glu) facilitated soma depolarization. When ejected with relatively higher currents than those needed to alter output-input ratios, EAAs decreased prepotential amplitudes while GABA produced increases in 16 of 18 neurons. Concurrent administration of both types (excitatory and inhibitory) of amino acid yielded enhanced soma spike activity due to Glu, concomitant with the enlarged prepotential amplitude caused by GABA. Tetrodotoxin (TTX) reversibly abolished soma spikes in 9 of 11 cases (but not fiber spikes). EAA antagonists exerted no effect upon output-input ratios or upon synaptic transmission. Glu and BMI both shortened the conversion time between prepotential and soma spike and increased the spike discharge rate. Whereas BMI did so in a stimulus- and input-related manner, high doses of Glu caused a continuous ongoing discharge until all spike activity stopped due to depolarization block. The results suggest that the output of thalamic VB neurons is controlled by GABA-mediated inhibitory processes, likely operating at the initial segment of the axon. This holds for thalamo-cortical relay neurons and presumed thalamic interneurons. Two processes appear to be in action: an intrinsic mechanism that operates tonically in VB to generally constrain the output of naturally-driven neurons, and a second mechanism that influences the strength of this GABA-mediated inhibition, thereby generating changes in the response repertoire of the neurons. This process appears to be to a large extent under the control of inputs from the neurons' peripheral receptive field.