Neurotrophic regulation of GABA receptors at a crayfish inhibitory synapse

Experiments were done on the inhibitory synapse of crayfish tonic muscle receptor organs (MROs) to determine whether gamma-aminobutyric acid (GABA) receptors would be affected by denervation or axotomy. It was found that severing the dorsal nerve containing the MRO sensory and inhibitory neurons usually induced, in 30 days or less, a dramatic transformation in the responses of MROs to ionophoretically applied GABA. In contrast to normal MROs which show only inhibitory responses to GABA, transformed MROs were substantially depolarized and excited by GABA application to numerous points found on the axon, soma, dendrites. Interspersed among the points of excitation, normal inhibitory points could still be found on the transformed cells. The results suggested that chronic lesions can induced structural changes in GABA receptors, whereby the Cl- ionophore is replaced by a cationic channel. It was possible to compare the effects of postsynaptic axotomy alone with those of postsynaptic plus presynaptic axotomy by testing MROs from animals whose ventral nerve cord was sectioned. These experiments suggested that interruption of the presynaptic neuron is an important factor in the transformation. It was not determined whether complete degeneration of the inhibitory synapse is necessary for the transformation, but the rapidity of the effect, coupled with the probability of long-term survival of synaptic contacts, suggested that complete degeneration was not necessary. Similarities were found in the GABA responses of transformed MROs and those MROs which normally receive no innervation, which are located in the sixth abdominal segment. These results support the idea that trophic regulation from inhibitory neurons is a factor in stabilizing the association of the Cl- ionophore with GABA receptor.