Synapse- and subtype-specific modulation of synaptic transmission by nicotinic acetylcholine receptors in the ventrobasal thalamus

The rodent thalamic ventrobasal complex (VB) which is a subdivision of somatosensory thalamus receives two excitatory inputs through the medial lemniscal synapse, which is a sensory afferent synapse, and the corticothalamic synapse from layer VI of the somatosensory cortex. In addition, the VB also receives cholinergic inputs from the brain stem, and nicotinic acetylcholine receptors (nAChRs) are highly expressed in the VB. Little is known, however, how acetylcholine (ACh) modulates synaptic transmission at the medial lemniscal and corticothalamic synapses in the VB. Furthermore, it remains unclear which subtype of nAChRs contributes to VB synaptic transmission. We report here that the activation of nAChRs presynaptically depressed corticothalamic synaptic transmission, whereas it did not affect medial lemniscal synaptic transmission in juvenile mice. This presynaptic modulation was mediated by the activation of nAChRs that contained α4 and β2 subunit, but not by α7 nAChRs. Moreover, galanthamine, an allosteric modulator of α4β2α5 nAChR, enhanced the ACh-induced depression of corticothalamic excitatory postsynaptic currents (EPSCs), indicating that α4β2α5 nAChRs at corticothalamic axon terminals specifically contribute to the depression of corticothalamic synaptic transmission.

Research highlights▶ nAChRs selectively and presynaptically depress corticothalamic synaptic transmission. ▶ In contrast, nAChRs does not affect medial lemniscal synaptic transmission. ▶ This presynaptic modulation is mediated by at least the activation of α4β2α5 nAChRs.