The mammalian neocortex is widely innervated by noradrenergic (NA) fibres from the locus coeruleus. To determine the effects of NA on vertical synaptic inputs to layer 4 (L4) cells from the ventrobasal (VB) thalamus and layer 2/3 (L2/3), thalamocortical slices were prepared and whole-cell recordings were made from L4 cells. Excitatory synaptic responses were evoked by electrical stimulation of the thalamus or L2/3 immediately above. Recorded cells were identified as regular spiking (RS), regular spiking non-pyramidal (RSNP) or fast spiking (FS) cells through their firing patterns in response to current injections. NA suppressed (∼50% of control) excitatory vertical inputs to all cell types in a dose-dependent manner. The presynaptic site of action of NA was suggested by three independent studies. First, responses caused by iontophoretically applied glutamate were not suppressed by NA. Second, paired pulse ratio was increased during NA suppression. Finally, a CV−2 (CV: coefficient of variation) analysis was performed. The resultant diagonal alignment of the ratio of CV−2 plotted against the ratio of the amplitude of postsynaptic responses suggests a presynaptic mechanism for the suppression. Experiments with phenylephrine (α1 agonist), prazosin (α1 antagonist), yohimbine (α2 antagonist) and propranolol (β antagonist) indicated that suppression was mediated by α2 adrenoceptor. To determine whether the α2A adrenoceptor subtype was involved, α2A adrenoceptor knockout mice were used. NA failed to suppress EPSCs in all cell types, suggesting an involvement of α2A adrenoceptor. Altogether, we concluded that NA suppresses vertical excitatory synaptic connections in L4 excitatory and inhibitory cells through presynaptic α2A adrenoceptor.
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