LESION-INDUCED TRANSIENT SUPPRESSION OF INHIBITORY FUNCTION IN RAT NEOCORTEX IN-VITRO

The structural and functional consequences of a local thermolesion wer e examined in rat neocortex with electrophysiological in votro techniq ues and immunocytochemistry. Age-matched untreated and sham-operated a nimals served as controls and were analysed in the same way. The lesio ns consisted of a core of coagulated tissue 2-3 mm in diameter and rea ched ventrally into the deep cortical layers. After two days reactive astrocytes and after nine days a dense gliosis were observed in the im mediate vicinity. Modifications in the intrinsic membrane characterist ics and the synaptic network properties were investigated with intra- and extracellular recording techniques after survival times of one to eight days. Neurons recorded in the surrounding of lesions in neocorti cal slices revealed a significantly more depolarized resting membrane potential and a higher neuronal input resistance. In comparison to cel ls in control slices, maximal discharge rates to injection of depolari zing current pulses of neurons close to a focal lesion were not signif icantly altered and intrinsic burst firing was never observed. However , between postlesion days 1 and 5, neurons in the surroundings of lesi ons showed a transient increase in synaptic excitability. This hyperac tivity was most clearly pronounced at a distance of 2-3 mm from the ce ntre of the lesion (i.e. about 1-1.5 mm away from the lesion border) a nd characterized by long-duration field potential responses and multip hasic long-lasting er;citatory postsynaptic potentials to orthodromic stimulation of the afferent input. This lesion-induced hyperexcitabili ty was associated with a significant reduction in the peak conductance of the Cl--dependent fast inhibitory postsynaptic potential and the K +-dependent long-latency inhibitory postsynaptic potential. suggesting that the intracortical GABAergic system was functionally impaired. Th e decrease in synaptic inhibition was associated with prolonged N-meth yl-D-aspartate receptor-mediated activity, which could be reversibly b locked by D-amino-phosphonovaleric acid. In addition, neurons recorded in the vicinity of the lesion responded to an orthodromic synaptic st imulus with a long-lasting burst. The lesion-induced disturbance in th e balance between the excitatory and inhibitory system may not only ha ve profound influences on the mechanisms of intracortical information processing, but may also lead to the expression of epileptiform activi ty and long-term functional deficits.