Dopamine receptors D1, D2, and D4 modulate electrical synapses and excitability in the thalamic reticular nucleus.

The thalamic reticular nucleus (TRN) is a thin shell of gap junction-coupled GABAergic inhibitory neurons that regulate afferent sensory relay of the thalamus. The TRN receives dopaminergic innervation from the midbrain, and it is known to express high concentrations of D1 and D4 receptors. Although dopaminergic modulation of presynaptic inputs to TRN has been described, the direct effect of dopamine on TRN neurons and its electrical synapses is largely unknown. Here, we confirmed D1 and D4 expression and showed that D2 receptors are also expressed in TRN. To characterize how dopamine affects both neuronal excitability and electrical synapse coupling strength in the TRN, we performed dual whole cell patch-clamp recordings of TRN neurons and injected them with 500-ms current pulses to measure input resistance, rheobase, spiking frequency, and coupling conductance. Measurements were taken before and after bath application of dopamine or agonists for either D1, D2, or D4 receptors. Our results show that bath application of dopamine did not consistently modulate excitability or electrical synapse strength. However, application of specific dopamine receptor agonists revealed that activation of D1 and D4 receptors increases input resistance and activation of D2-like receptors lowers maximum tonic spike rate. Notably, D2 and D4 receptors depressed electrical synapses. Together, our results suggest that coactivation of D1, D2, and D4 receptors may result in cross talk due to opposing signaling cascades. Furthermore, we show that selective dopamine receptor engagement has substantial potential to modulate TRN circuitry. Postsynaptic modulation of TRN neurons by activation of specific DA receptor subtypes has not been previously determined. Our research identifies that a previously unreported D2 receptor is expressed in TRN, and we found that D1, D2, and D4 receptors impose distinct excitability changes on TRN. Furthermore, D2 and D4 receptors depress electrical synapses in TRN, identifying a new substrate for modulation of intra-TRN communication.