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

The hypothesis has been tested that inhibitory mechanisms, active spat ially and temporally between the input and the output of thalamic neur ons, determine the nature of the information transmitted to the cerebr al cortex. To enable this assessment, in barbiturate-anesthetized cats and urethane-anesthetized rats juxtacellular recordings were performe d together with microiontophoretic ejection of transmitter agonists an d antagonists. The effects of these drugs were studied on responses ev oked by mechanical stimulation of cutaneous receptive fields (RFs) of neurons in the thalamic ventrobasal complex (VB). Neurons from differe nt parts of the VB were investigated: 29 units were located medially, in the ventral posteromedial nucleus (VPM; facial RFs), and 11 units w ere located laterally, in the ventral posterolateral nucleus (VPL; for epaw and body RFs). A further eleven VB units had no detectable RF. Tw enty-six neurons were tested with electrical stimulation of the somato sensory cortex (SI), 17 of these being identified as thalamo-cortical relay neurons and 5 being classified as presumed interneurons; the rem aining 4 could not be activated. Four additional recordings were from trigemino-thalamic or thalamo-cortical fibers. For the quantitative as sessment of the neurons' input and output, neuronal activity was induc ed by feedback-controlled, mechanical trapezoidal and/or sinusoidal st imuli applied to sinus hairs, fur or skin and the numbers of prepotent ials and soma spikes were compared in peristimulus time histograms (PS THs) generated simultaneously for both types of signal from 'DC' recor dings. Iontophoretic administration of excitatory amino acids (EAAs) o r 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 susta ined-to-transient response pattern, changes to sustained-to-sustained patterns were demonstrated. Tests with gammaaminobutyric acid (GABA) p roduced 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 p attern. For cortically evoked antidromic spikes of VB neurons, GABA pr oduced a failure of the initial segment (IS-) spike to invade the soma , whereas BMI and glutamate (Glu) facilitated soma depolarization. Whe n ejected with relatively higher currents than those needed to alter o utput-input ratios, EAAs decreased prepotential amplitudes while GABA produced increases in 16 of 18 neurons. Concurrent administration of b oth types (excitatory and inhibitory) of amino acid yielded enhanced s oma spike activity due to Glu, concomitant with the enlarged prepotent ial amplitude caused by GABA. Tetrodotoxin (TTX) reversibly abolished soma spikes in 9 of 11 cases (but not fiber spikes). EAA antagonists e xerted no effect upon output-input ratios or upon synaptic transmissio n. Glu and BMI both shortened the conversion time between prepotential and soma spike and increased the spike discharge rate. Whereas BMI di d so in a stimulus- and input-related manner, high doses of Glu caused a continuous ongoing discharge until all spike activity stopped due t o depolarization block. The results suggest that the output of thalami c VB neurons is controlled by GABA-mediated inhibitory processes, like ly operating at the initial segment of the axon. This holds for thalam o-cortical relay neurons and presumed thalamic interneurons. Two proce sses appear to be in action: an intrinsic mechanism that operates toni cally in VB to generally constrain the output of naturally-driven neur ons, and a second mechanism that influences the strength of this GABA- mediated inhibition, thereby generating changes in the response repert oire of the neurons. This process appears to be to a large extent unde r the control of inputs from the neurons' peripheral receptive field.