The action of ethosuximide (ETX) on Na⁺, K⁺, and Ca²⁺currents and on tonic and burst-firing patterns was investigated in rat and cat thalamic neuronsin vitroby using patch and sharp microelectrode recordings. In thalamocortical (TC) neurons of the rat dorsal lateral geniculate nucleus (LGN), ETX (0.75–1 mm) decreased the noninactivating Na⁺current,I_NaP, by 60% but had no effect on the transient Na⁺current. In TC neurons of the rat and cat LGN, the whole-cell transient outward current was not affected by ETX (up to 1 mm), but the sustained outward current was decreased by 39% at 20 mV in the presence of ETX (0.25–0.5 mm): this reduction was not observed in a low Ca²⁺(0.5 mm) and high Mg²⁺(8 mm) medium or in the presence of Ni²⁺(1 mm) and Cd²⁺(100 μm). In addition, ETX (up to 1 mm) had no effect on the low-threshold Ca²⁺current,I_T, of TC neurons of the rat ventrobasal (VB) thalamus and LGN and in neurons of the rat nucleus reticularis thalami nor on the high-threshold Ca²⁺current in TC neurons of the rat LGN.Sharp microelectrode recordings in TC neurons of the rat and cat LGN and VB showed that ETX did not change the resting membrane potential but increased the apparent input resistance at potentials greater than −60 mV, resulting in an increase in tonic firing. In contrast, ETX decreased the number of action potentials in the burst evoked by a low-threshold Ca²⁺potential. The frequency of the remaining action potentials in a burst also was decreased, whereas the latency of the first action potential was increased. Similar effects were observed on the burst firing evoked during intrinsic δ oscillations.These results indicate an action of ETX onI_NaPand on the Ca²⁺-activated K⁺current, which explains the decrease in burst firing and the increase in tonic firing, and, together with the lack of action on low- and high-threshold Ca²⁺currents, the results cast doubts on the hypothesis that a reduction ofI_Tin thalamic neurons underlies the therapeutic action of this anti-absence medicine.

The molecular pathways underlying the induction and maintenance of long-term synaptic plasticity have been extensively investigated revealing various mechanisms by which neurons control their synaptic strength. The dynamic nature of neuronal connections combined with plasticity-mediated long-lasting structural and functional alterations provide valuable insights into neuronal encoding processes as molecular substrates of not only learning and memory but potentially other sensory, motor and behavioural functions that reflect previous experience. However, one key element receiving little attention in the study of synaptic plasticity is the role of neuromodulators, which are known to orchestrate neuronal activity on brain-wide, network and synaptic scales. We aim to review current evidence on the mechanisms by which certain modulators, namely dopamine, acetylcholine, noradrenaline and serotonin, control synaptic plasticity induction through corresponding metabotropic receptors in a pathway-specific manner. Lastly, we propose that neuromodulators control plasticity outcomes through steering glutamatergic transmission, thereby gating its induction and maintenance.