Myelination defects and neuronal hyperexcitability in the neocortex of connexin 32-deficient mice

Morphological and electrophysiological studies were performed on neocortice s of adult Connexin 32 (Cx32)-deficient mice and wild-type mice to investig ate the consequences of a lack of the gap junction subunit Cx32 on neocorti cal structure and function. Morphometrical analysis revealed a reduced volu me fraction of myelin within the neuropil and a decreased thickness of the axonal myelin sheaths in the neocortex of Cx32-deficient mice. Intracellula r recordings from neurons in neocortical slice preparations provided eviden ce for an increased membrane input resistance in neurons of Cx32-null mutan t mice as compared to neurons of wild-type mice. Consequently, neurons of C x32-deficient mice displayed an enhanced intrinsic excitability. In additio n, similar to 50% of the neurons investigated in slices of Cx32-deficient m ice responded to afferent stimulation with delayed and large glutamatergic excitatory postsynaptic potentials resembling paroxysmal depolarizations. G ABAergic inhibition sufficient to efficiently control synaptic excitability was virtually absent in these cells. The changes in intrinsic membrane pro perties observed in neurons of Cx32-null mutant mice were independent of th e alterations in synaptic function, since increased membrane resistances we re observed also in neurons with normal synaptic response pattern. Thus, in the neocortex, lack of Cx32 correlates with myelination defects, alteratio ns in intrinsic membrane properties and dysfunction of inhibitory synaptic transmission.